vitamin-k-semiquinone-radical and Thrombosis

The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.. The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.. Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I. Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K

Thromboembolic events in myeloproliferative neoplasms (MPNs) are one of the most important causes of mortality and morbidity, in which vitamin K antagonists (VKAs) have been used mostly. Recently, direct oral anticoagulants (DOACs) are used in venous thromboembolism (VTE) and cancer-associated thrombosis (CAT). With the adoption of data from CAT and VTE, the usage of DOACs in MPNs is increasing.. In this paper, we performed a systematic review to the current literature regarding the usage of DOACs in MPNs. Eleven studies involving 944 patients were included. The reasons for initiating DOACs were secondary prophylaxis for thrombosis (arterial or venous) and atrial fibrillation (AF) in 562 and 382 patients, respectively. A total of 84 (8.9%) recurrent thrombotic (arterial or venous) events recorded. Forty-six (8.1%) events occurred in the thrombosis group (arterial or venous) and 38 (9.9%) events occurred in patients with AF.. Ease of management and patient comfort should be regarded as benefits of DOACs compared to VKAs. However, it would be appropriate to bring an individualized approach until we obtain high-quality data with prospectively designed studies involving more patients and longer follow-up time concerning the use of DOACs in patients with MPNs.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Myeloproliferative Disorders; Neoplasms; Thrombosis; Venous Thromboembolism; Vitamin K

Aim    To perform a systematic review and meta-analysis of efficacy and safety of direct oral anticoagulants (DOAC) as compared to vitamin K antagonists (VKA) in the treatment of left ventricular (LV) thrombosis.Material and methods    A search was performed in PubMed and Google Scholar for studies that compared DOAC and VKA in the treatment of LV thrombosis with respect of thromboembolic events, hemorrhagic complications, and thrombus resolution. The effect was evaluated with the odds ratio (OR) that was computed using a fixed effects model.Results    For these systematic review and meta-analysis, 19 studies were selected, including 2 randomized and 17 cohort studies. The articles included into these systematic review and meta-analysis, were published from 2018 through 2021. In total, 2970 patients (mean age, 58.8 лет; 1879 (61.2 %) men) with LV thrombus were included into the meta-analysis. Mean follow-up duration was 17.9 months. The meta-analysis showed no significant difference between DOAC and VKA in the incidence of the study outcomes: thromboembolic events (OR, 0.86; 95 % CI: 0.67-1.10; р=0.22), hemorrhagic complications (OR, 0.77; 95 % CI: 0.55-1.07; р=0.12), thrombus resolution (OR, 0.96; 95 % CI: 0.76-1.22; р=0.77). In a subgroup analysis, rivaroxaban compared to VKA significantly (79%) reduced the risk of thromboembolic complications (OR, 0.21; 95 % CI: 0.05-0.83; р=0.03) with no significant differences in hemorrhagic events (OR, 0.60; 95 % CI: 0.21-1.71; р=0.34) or thrombus resolution (OR, 1.44; 95 % CI: 0.83-1.31; р=0.20). The apixaban treatment group had significantly more (4.88 times) cases of thrombus resolution than the VKA treatment group (OR, 4.88; 95 % CI: 1.37-17.30; р=0.01); for apixaban, data on hemorrhagic and thromboembolic complications were not available.Conclusions    The therapeutic efficacy and side effects of the DOAC treatment for LV thrombosis were similar to those of VKA with respect of thromboembolic events, hemorrhage, and thrombus resolution.

Topics: Anticoagulants; Female; Fibrinolytic Agents; Heart Diseases; Humans; Male; Middle Aged; Thromboembolism; Thrombosis; Vitamin K

We conducted a systematic review and meta-analysis of randomized controlled trials comparing direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) in the first 90 days after bioprosthetic valve implantation.. We systematically searched Embase, Medline and CENTRAL. We screened titles, abstracts and full texts, extracted data and assessed the risk of bias in duplicate. We pooled data using the Mantel-Haenzel method and random effects modelling. We conducted subgroup analyses based on the type of valve (transcatheter versus surgical) and timing of initiation of anticoagulation (<7 vs >7 days after valve implantation). We assessed the certainty of evidence using the Grading of Recommendations, Assessments, Development and Evaluation approach.. We included 4 studies of 2284 patients with a median follow-up of 12 months. Two studies examined transcatheter valves (1877/2284 = 83%) and 2 examined surgical valves (407/2284 = 17%). We found no statistically significant differences between DOACs and VKAs with regard to thrombosis, bleeding, death or subclinical valve thrombosis. However, there was a subgroup trend towards more bleeding with DOACs when initiated within 7 days of valve implantation.. In the existing randomized literature on DOACs versus VKAs in the first 90 days after bioprosthetic valve implantation, there appears to be no difference with regard to thrombosis, bleeding or death. Interpretation of the data is limited by small numbers of events and wide confidence intervals. Future studies should focus on surgical valves and should include long-term follow-up to assess any potential impact of randomized therapy on valve durability.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Thrombosis; Vitamin K

Khairani CD, Bejjani A, Piazza G, et al.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Humans; Thrombosis; Vitamin K

Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs versus vitamin K antagonists (VKAs) in LVT treatment.. Systematic search of studies evaluating DOACs versus VKAs use in patients with LVT was performed on May 11. Twenty studies were included in the meta-analysis: 1,391 patients were treated with DOACs and 1,534 with VKAs. A significant reduction in the risk of ischemic stroke (OR 0.67, 95% CI, 0.45-0.98, P=0.048, number needed to treat to benefit [NNTB] 22 [95% CI 15-43]) and any bleeding (OR 0.64, 95% CI 0.46-0.89, P=0.009, NNTB 26 [95% CI 16-80]) was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints.. Compared to VKAs, DOACs are associated with a reduced risk of ischemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

Topics: Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Stroke; Thrombosis; Vitamin K

Left ventricular thrombi (LVTs) increase the risk of stroke, systemic embolism, and subsequent death. Current guidelines recommend vitamin K antagonists (VKAs) as first-line treatment for LVT. Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin for the treatment of LVT. However, the efficacy and safety of DOACs versus VKAs remain controversial. Thus, we conducted an updated meta-analysis of DOACs versus VKAs for LVT treatment. We systematically searched PubMed, Embase, ClinicalTrials, and Cochrane Library databases for relevant articles published before December 11, 2021. The relative risks (RRs) with 95% confidence intervals (CIs) were calculated for each study. The meta-analysis included 12 cohort studies and 3 randomized controlled trials with a total of 2334 patients. We found that DOACs had a lower risk of clinically significant bleeding than VKAs (RR = 0.6; 95% CI, 0.39 to 0.90; P = 0.01; I2 = 0%). There was no difference in LVT resolution (RR = 1.01; 95% CI, 0.93 to 1.09; P = 0.48; I2 = 0%), stroke and/or systematic embolic events (RR = 0.87; 95% CI, 0.11 to 1.55; P = 0.2; I2 = 30%), and all-cause mortality (RR = 0.9; 95% CI, 0.58 to 1.4; P = 0.65; I2 = 0%). Overall, DOACs are noninferior to warfarin in LVT treatment but have a lower risk of clinically significant bleeding. This suggests that DOACs might be better alternatives to warfarin for LVT treatment.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Thrombosis; Vitamin K; Warfarin

Direct oral anticoagulants (DOACs) are the guideline-recommended therapy for some hypercoagulable diseases but are used off-label for left ventricular thrombus (LVT) owing to a paucity of evidence. We performed a meta-analysis to assess the safety and efficacy of DOACs compared with vitamin K antagonists (VKAs) for LVT treatment.. We comprehensively searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for studies that compared DOACs with VKAs for LVT treatment. Outcome indicators included stroke or systemic embolism (SSE), thrombus resolution, bleeding, and death. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. Data were analyzed using Review Manager 5.3, and the meta-analysis is registered at PROSPERO (CRD 42020211376).. We included 12 observational studies (n = 2262 patients). SSE was similar for DOACs and VKAs groups (odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.66-1.54, P = 0.95). For thrombus resolution, DOACs were not significantly different to VKAs (OR = 1.15, 95% CI 0.54-2.45, P = 0.71). DOACs and VKAs had a similar bleeding risk (OR = 0.78, 95% CI 0.45-1.35, P = 0.37). DOACs and VKAs groups had a comparable mortality (OR = 0.91, 95% CI 0.50-1.65, P = 0.76). Subgroup analysis showed that post-acute myocardial infarction (AMI) patients using DOACs had a lower risk of SSE (OR = 0.24, 95% CI 0.07-0.87, P = 0.03) and bleeding (OR = 0.38, 95% CI 0.18-0.81, P = 0.01).. DOACs and VKAs showed no difference in the safety and efficacy of patients with LVT. DOACs might be superior to VKAs for LVT treatment in post-AMI patients.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Stroke; Thrombosis; Vitamin K; Vitamins

This paper aims to provide a narrative review of the risks, diagnosis, and management of recurrent venous thromboembolism (VTE) in cancer patients. There is an established association between cancer and VTE, with cancer being a major risk factor for VTE. A history of VTE, short duration of oral anticoagulation, and a proximal DVT are all associated with increased risk for recurrent VTE. Studies have shown that certain cancers (e.g., metastatic genitourinary, lung, and colorectal cancers) are associated with recurrent VTE. Published literature shows that cancer is prothrombotic, and various mechanisms have been postulated as pathways for increased thrombogenesis and hence recurrent VTE in cancer. The symptoms, signs, laboratory information, and imaging results for the diagnosis of recurrent VTE are similar to those of an initial VTE. Management of recurrent VTE involves using low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). Vitamin K antagonists (VKA) or inferior vena cava (IVC) filters are less commonly used.

Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Recurrence; Thrombosis; Venous Thromboembolism; Vitamin K

One of the most catastrophic complications of Atrial fibrillation (AF) is thromboembolic stroke. Current guidelines recommend that 3 weeks of anticoagulation is adequate prior to direct current cardioversion (DCCV) to prevent thromboembolism. Here we present data regarding, which anticoagulant is most likely to show a presence of an Left atrial appendage thrombus (LAAT) on trans esophageal echocardiogram (TEE) for DCCV despite 3 weeks of anticoagulation.. To investigate the effectiveness of both vitamin k antagonist (VKA) and direct oral anticoagulants (DOAC) in patients with AF as an anticoagulant for LAAT after 3 weeks of medication.. This is a single-high volume tertiary center, where TEE precardioversion is the standard practice. We reviewed data over 10 months where DCCV was intended on individuals with AF who were fully anticoagulated for at least 3 weeks with either a VKA or taking a DOAC.. The data showed a statistical difference between patients who were fully anticoagulated for at least 3 weeks with VKA in comparison to DOACs. Patients on DOACs are significantly less likely to have an LAAT after at least 3 weeks of anticoagulation. OR = 0.04 (CI 95% 0.005-0.42; p-value < .05). Despite anticoagulation for at least 3 weeks, 40% of our patients still had a LAAT.. Our data indicates that all patients should be required to undergo a TEE prior to DCCV. This data also adds to the current evidence and supports the use of DOAC in AF to prevent LAAT.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Electrocardiography; Fibrinolytic Agents; Heart Diseases; Humans; Incidence; Thrombosis; Vitamin K

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious. We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types. A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49-8.93; I2  = 29%, P  = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56-4.42; I2  = 0, P  = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99-10.29; I2  = 0, P  = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences. In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Rivaroxaban; Thrombosis; Venous Thromboembolism; Vitamin K

Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT.. We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed.. Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.

Topics: Anticoagulants; Embolism; Hemorrhage; Humans; Stroke; Thrombosis; Vitamin K

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.

Topics: American Heart Association; Anticoagulants; Heart Ventricles; Humans; Platelet Aggregation Inhibitors; Thrombosis; Vitamin K; Warfarin

The use of direct oral anticoagulants (DOAC) in preference to vitamin K antagonists (VKA) as a treatment of left ventricle (LV) thrombus is controversial.. Literature search for full-text articles and conference abstracts was performed using PubMed, EMBASE databases search was performed to identify articles that compared use of DOAC vs. VKA in patients with LV thrombus. The primary outcome was composite failure or adverse effects of DOAC and VKA. Other outcomes were resolution of thrombus, systemic thromboembolism, major bleeding, and mortality. Pooled odds ratio (OR) with 95% confidence interval (CI) were computed using random effects model.. Seven studies with 1003 patients (mean age DOAC = 58.8 years and VKA = 58.9 year, 55.5% males) were included in this study. There were 306 (30.5%) patients that were treated with DOAC and 697 (69.5%) patients were treated with VKA. Overall, there were no significant differences between both agents in terms of composite failure/adverse effects, resolution of thrombus, systemic embolism, major bleeding, or mortality.. In this pooled analysis, outcomes in patients on DOAC were comparable to VKA. The hypothesis generated could suggest DOAC could be used interchangeably with VKA in patients with LV thrombus. Randomized trials are needed for generalization of results.

Topics: Administration, Oral; Anticoagulants; Female; Heart Ventricles; Humans; Male; Middle Aged; Thrombosis; Vitamin K

To compare the safety and efficacy of direct oral anticoagulants (DOAC) relative to vitamin K antagonists (VKA) for the treatment of left ventricular thrombus (LVT).. This retrospective study enrolled patients diagnosed with LVT from 2014-2017. Patient characteristics and outcomes within 12 months of LVT diagnosis were recorded and analyzed. A meta-analysis was also performed by pooling our results with existing data in literature.. 14 DOAC and 59 VKA patients were included. Baseline demographic and clinical characteristics were similar except for age. Although more strokes within 12 months occurred in VKA (15%) than in DOAC (0%) patients, this was not statistically significant (. Our study and meta-analysis suggest similar efficacy and safety of DOACs in the treatment of LVT compared to VKA. These findings underscore the need for a randomized controlled trial.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Coronary Thrombosis; Female; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

 To undertake a systematic review and meta-analysis to assess the satisfaction of patients receiving nonvitamin K anticoagulants (NOACs), compared with vitamin K antagonists (VKAs)..  We searched CENTRAL, MEDLINE, Embase, and Clinicaltrials.gov for randomized controlled trials (RCTs) and observational studies. Two reviewers screened, extracted, and appraised data independently. We pooled data using a random-effects model. Outcome included treatment satisfaction, which was assessed by scores of Duke Anticoagulation Satisfaction Scale (DASS), Anticlot Treatment Scale (ACTS), Perception of Anticoagulant Treatment Questionnaire 2 (PACT-Q2), or Treatment Satisfaction Questionnaire for Medication version II (TSQM-VII) and their domains reported with 95% confidence intervals (95% CIs). We followed MOOSE and PRISMA guidelines..  In patients with nonvalvular atrial fibrillation or venous thromboembolism, NOAC treatment is associated with greater satisfaction compared with VKAs. The switch from VKAs to NOACs was associated with improved patients' satisfaction. These effects were largely due to a lower degree of treatment burden with NOAC treatment.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Patient Satisfaction; Thrombosis; Treatment Adherence and Compliance; Venous Thromboembolism; Vitamin K

Left ventricular thrombus (LVT) is a complication of multiple cardiovascular diseases. There has been an increasing trend of off-label using direct-acting oral anticoagulants (DOACs) for the treatment of patients with LVT. The effectiveness and safety of DOACs remain to be determined.. We searched for publications (PubMed, MEDLINE, Web of Science, EMBASE, Scopus, and ClinicalTrials.gov) comparing DOACs with Vitamin K antagonists (VKAs) in patients with LVT. We estimated odds ratio (OR) and 95% confidence intervals (CIs) for stroke, systemic embolism, major bleeding events, and thrombus resolution as the effectiveness and safety outcomes. The subgroup analysis and meta-regression were also performed.. Nine retrospective observational studies with a total of 2028 participants were included. DOACs demonstrated a similar risk of stroke, systemic embolism, major bleeding events, and thrombus resolution (OR = 0.79, 95% CI: 0.50-1.23; OR = 1.22, 95% CI: 0.65-2.26; OR = 0.82, 95% CI: 0.47-1.42; OR = 1.34, 95% CI: 0.62-2.90, respectively).. There is no difference between DOACs and VKAs in patients with LVT from the perspectives of stroke, systemic embolism, major bleeding events, and thrombus resolution. Prospective randomized controlled trials with adequate sample sizes are urgently needed to confirm findings.

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Prospective Studies; Retrospective Studies; Thrombosis; Vitamin K

Topics: Anticoagulants; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Current guidelines recommend vitamin K antagonists (VKAs) for left ventricular thrombus (LVT) resolution. Direct oral anticoagulants (DOACs) are increasingly evaluated as alternatives to the standard of care in anticoagulation.. We performed a systematic review and meta-analysis to assess the use of DOACs vs VKAs for LVT treatment. The occurrence of LVT resolution, systemic embolism (SE) or stroke, and bleeding events were compared during follow-up using random-effects analysis.. The 5 included studies were all observational (a total of 828 patients). Of these, 284 patients (34%) were treated with DOACs, and 544 (66%) treated with VKAs. Thrombus resolution was similar for both methods (pooled odds ratio [OR], 0.91; 95% CI, 0.47-1.75;. Our systematic review and meta-analysis suggests DOACs were as effective as VKAs for LVT resolution, with a similar risk of systemic embolism/stroke and clinically relevant bleeding. These results, obtained from observational studies, are not definitive and hence randomized controlled trials are needed. Nevertheless, our analysis identifies key experimental features required in future studies.

Topics: Administration, Oral; Age Factors; Anticoagulants; Diabetes Mellitus; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Hypertension; Platelet Aggregation Inhibitors; Sex Factors; Stroke; Thrombosis; Vitamin K

Direct oral anticoagulants (DOACs) have a well-established role in the treatment of deep vein thrombosis and pulmonary embolism and in the reduction of thromboembolism in nonvalvular atrial fibrillation. However, limited evidence supports their role in patients with left ventricular thrombi.. The PubMed, EMBASE, and Cochrane databases were searched for relevant articles published from inception to 1 August 2020. We included studies evaluating the effect of DOACs versus vitamin K antagonists (VKAs) in patients with left ventricular thrombi. The primary outcome was thrombus resolution, and the secondary outcomes were major bleeding and stroke or systemic embolization (SSE).. Five retrospective observational studies were included, with a total of 857 patients. VKAs and DOACs had a similar rate of thrombus resolution (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.57-1.65; p = 0.90). Our analysis also demonstrated a similar rate of major bleeding (OR 0.62; 95% CI 0.27-1.44; p = 0.27) and SSE (OR 1.86; 95% CI 0.99-3.50; p = 0.05) between the two treatment groups.. In patients with left ventricular thrombi, DOACs and VKAs are associated with similar rates of thrombus resolution, major bleeding, and SSE.

Topics: Anticoagulants; Factor Xa Inhibitors; Heart Ventricles; Hemorrhage; Humans; Observational Studies as Topic; Retrospective Studies; Thrombosis; Vitamin K

Current guidelines recommend vitamin K antagonists (VKAs) to reduce the risk of systemic thromboembolic (STE) events in patients with left ventricular (LV) thrombus. Direct oral anticoagulants (DOACs) are an emerging alternative to VKAs; however, data supporting DOAC use in LV thrombus are still lacking. We conducted this systematic review and meta-analysis to compare the efficacy and safety between DOACs and VKAs in this population.. We searched MEDLINE, Embase, and the Cochrane Library databases from inception to October 2020 to identify studies that compared clinical outcomes of interest, including stroke or any STE, LV thrombus resolution, and bleeding, between patients who used DOACs and VKAs for LV thrombus. Data from each study were combined using the random-effects model.. Our meta-analysis found no significant differences in rates of STE events, LV thrombus resolution, or bleeding events between the use of DOACs and VKAs in LV thrombus. Further randomised controlled trials are needed to confirm our findingsHighlightsThere is limited evidence comparing the use of direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) in left ventricular (LV) thrombus.Our systematic review and meta-analysis showed that DOACs are not inferior to VKAs in the incidence of systemic thromboembolism (STE), the rate of LV thrombus resolution, and the risk of bleeding.Current evidence is based on observational studies only. Further randomised controlled trials are needed to confirm the findings.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Though current guidelines currently recommend using warfarin, there is also a growing interest in the utilization of direct oral anticoagulants (DOACs) to treat left ventricular (LV) thrombus.. We performed a systematic search using PubMed, SCOPUS, EMBASE, Google Scholar, and ClinicalTrials.gov from inception to September 30, 2020, for studies that had reported outcomes in patients with left ventricular thrombus treated with DOACs (PROSPERO registration number CRD42020219761).. Twelve studies (n = 867 patients) were included in the analysis. The pooled incidence of the systemic embolic events (SEE) with DOACs was 2.7%, whereas the thrombus resolution rate was 86.6%. The pooled incidence of overall bleeding (composite of major and minor bleeding) and major bleeding with DOACs were 5.6% and 1.1%, respectively. No significant difference was observed in terms of SEE (OR 0.81, 95% confidence interval [CI] 0.44-1.52, p = .54), major bleeding (OR 0.29, 95% CI 0.07-1.26, p = .24), and failure of LV thrombus resolution (OR 0.86, 95% CI 0.28-2.58, p = .68); whereas overall bleeding was significantly low in patients with LV thrombus treated with DOACs compared to vitamin K antagonists (VKAs) (OR 0.33, 95% CI 0.14-0.81, p = .02).. Our study demonstrates no significant difference in SEE, major bleeding, or failure of LV thrombus resolution between the two groups, thus demonstrating that DOACs are an efficacious and safe alternative for the treatment of LV thrombus compared to VKAs. However, further well-designed prospective trials are needed to answer important clinical questions-optimal dosing/duration of DOACs and its safety in the background of antiplatelet therapy.

Topics: Administration, Oral; Anticoagulants; Humans; Prospective Studies; Thrombosis; Vitamin K

Although several studies have assessed the effect of non-vitamin K antagonist oral anticoagulants (NOACs) relative to that of vitamin K antagonists (VKAs) in patients with left ventricular thrombus, the results remain controversial. Herein, a meta-analysis was performed to compare the effectiveness and safety of NOACs versus VKAs for the treatment of left ventricular thrombus. We systematically searched the Cochrane Library, PubMed and Embase databases until November 2020 for studies that compared the effects of NOACs versus VKAs in patients with left ventricular thrombus. The treatment effects were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) and pooled by a random-effects model. Seven retrospective studies involving 865 patients with left ventricular thrombus (266 NOAC and 599 VKA users) were included. The pooled analysis suggested no difference in the rate of thrombus resolution between the NOAC and VKA groups (OR = 0.83, 95% CI 0.61-1.13). There were also no differences in the rates of stroke or systemic embolism (OR = 0.62, 95% CI 0.20-1.97), bleeding events (OR = 0.73, 95% CI 0.37-1.45), or all-cause death (OR = 0.92, 95% CI 0.50-1.69) between patients treated with NOACs and those treated with VKAs. In addition, the rates of thrombus resolution, stroke or systemic embolism, bleeding events, and all-cause death between NOAC- and warfarin-treated patients were also similar. Our current evidence suggested that NOAC and VKA users had similar rates of thrombus resolution and clinical outcomes among patients with left ventricular thrombus. Further large-scale prospective studies should confirm our results.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Prospective Studies; Retrospective Studies; Stroke; Thrombosis; Vitamin K

Although vitamin K antagonists (VKAs) are recommended as first-line anticoagulants for patients with left ventricular thrombus (LVT), accumulating evidence suggests direct oral anticoagulants (DOACs) could be safe alternatives for VKAs. Efficacy and safety of DOACs should be assessed to justify their usage for LVT patients.. To compare the efficacy and safety of DOACs and VKAs for the treatment of LVT.. We performed a meta-analysis of observational studies to compare DOACs to VKAs in LVT patients. The PubMed and EMBASE databases were searched for articles published until November 12, 2020. Pooled effects were estimated using Mantel-Haenszel method and presented as risk ratios (RR) using fixed-effect model. Reporting followed the Meta-analyses of observational studies in epidemiology (MOOSE) guideline.. A total of 2467 LVT patients from 13 studies were included. Compared with VKAs, DOACs showed similar efficacy in prevention of stroke or systemic embolism (RR: 0.96, 95% confidence interval [CI]: 0.80-1.16, P = 0.68) and thrombus resolution (RR: 0.88, 95% CI: 0.72-1.09, P = 0.26), but significantly lower risk of stroke (RR: 0.68, 95% CI: 0.47-1.00, P = 0.048). For safety outcomes, DOAC users showed similar risk of any bleedings (RR: 0.94, 95% CI: 0.67-1.31, P = 0.70), but lower risk of clinically relevant bleedings (RR: 0.35, 95% CI: 0.13-0.92, P = 0.03) compared with VKA users.. Compared with VKAs, DOACs acquired similar efficacy and safety profile for patients with LVT, but could reduce the risk of strokes and clinically relevant bleedings.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Left ventricular thrombus (LVT) may develop in systolic heart failure or after acute myocardial infarction. The current recommendations support the use of vitamin K antagonists (VKAs) for the treatment of LVT. Limited data exist regarding the use of direct oral anticoagulants (DOACs) in patients with LVT. This meta-analysis aims to investigate the efficacy and safety of DOACs versus VKAs for LVT.. We performed a comprehensive literature search using PubMed, Embase, and Cochrane Library databases through November 2020 for all studies that evaluated the efficacy and safety of DOACs versus VKAs in patients with LVT. The primary outcomes were LVT resolution, overall thromboembolic events, and thromboembolic stroke. The secondary outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effects model. Heterogeneity was assessed by I2 statistic.. A total of 11 studies including 2153 patients with LVT on anticoagulation (570 on DOACs vs. 1583 on VKAs) were included. LVT resolution was significantly higher in DOACs compared with VKAs [RR: 1.18 (95% CI: 1.04-1.35); P = 0.01, I2 = 25%]. However, no significant difference existed between DOACs and VKAs regarding overall thromboembolic events [RR: 1.10 (95% CI: 0.75-1.62); P = 0.61, I2 = 0%] and thromboembolic stroke [RR: 0.63 (95% CI: 0.39-1.02); P = 0.06, I2 = 0%]. Major bleeding [RR: 1.00 (95% CI: 0.66-1.51); P = 0.99, I2 = 4%] and all-cause mortality [RR: 0.84 (95% CI: 0.50-1.43); P = 0.53, I2 = 0%] were similar between the 2 groups.. DOACs seem to be more efficacious in achieving LVT resolution compared with VKAs. However, there was no significant difference between the 2 groups in thromboembolic events, major bleeding, and all-cause mortality. Randomized controlled trials are needed to confirm our findings.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Although several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus (LVT), those meta-analyses included no single-arm studies.. PubMed, Scopus, and the Cochrane Library databases were searched for articles investigating thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, or all-cause death in LVT treated with VKAs or DOACs, and single-class meta-analyses were also included (PROSPERO database, CRD42021230849). Event rates were pooled using a random effects model. Meta-regression analysis was performed to explore factors that may influence outcomes. 2,612 patients from 23 articles were included (VKAs: 2,004, DOACs: 608). There were no significant differences between VKAs and DOACs in the frequency of thrombus resolution (VKAs: 0.75 [95% confidence interval; 0.67 to 0.81], DOACs: 0.75 [0.67 to 0.82]), stroke (VKAs: 0.06 [0.04 to 0.10], DOACs: 0.02 [0.01 to 0.01]), any thromboembolism (VKAs: 0.08 [0.05 to 0.13], DOACs: 0.03 [0.01 to 0.10]), major bleeding (VKAs: 0.06 [0.04 to 0.09], DOACs: 0.03 [0.01 to 0.06]), any bleeding (VKAs: 0.08 [0.05 to 0.12], DOACs: 0.08 [0.06 to 0.10]), and all-cause death (VKAs: 0.07 [0.04 to 0.13], DOACs: 0.09 [0.05 to 0.16]). Meta-regression analysis revealed that increased duration of follow-up was associated with lower-rates of stroke (estimate: -0.040, p = 0.0495) with VKAs, but not with DOACs. There was significant publication bias for thrombus resolution, stroke, any thromboembolism, any bleeding, and all-cause death.. Efficacy and adverse outcomes of therapy with DOACs and VKAs do not differ. Randomized controlled trials are needed to determine the optimal anticoagulant strategy.

Topics: Administration, Oral; Anticoagulants; Heart Ventricles; Hemorrhage; Humans; International Normalized Ratio; Stroke; Thromboembolism; Thrombosis; Vitamin K

Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic.. The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research.. Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Child; Humans; Prospective Studies; Thrombosis; Vitamin K

Transcatheter aortic valve implantation (TAVI) has been a favored option for the patient who suffered from symptomatic aortic stenosis. However, the efficacy and safety outcomes in novel oral anticoagulants (NOACs) versus Vitamin-K antagonist (VKA) for post-TAVI patients are still controversial. This meta-analysis aims at comparing the clinical outcome and safety of NOACs and VKA in the patients after receiving TAVI.. We searched literature articles in all reachable databases, and observational study as well as randomized controlled trial would be included in order to perform a comprehensive analysis. All-cause mortality, major or life-threatening bleeding, disabling or nondisabling stroke were main pooled outcome measures. Subgroup analysis and meta-regression were adopted to explore heterogeneity. Assessment of bias was performed under the suggestion of Cochrane's Collaboration Tool.. With corroborative analysis of severe complications, VKA is shown to be more protective on post-TAVI patients in disabling or nondisabling stroke scenario but not in mortality or bleeding event.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve Stenosis; Female; Hemorrhage; Humans; Male; Risk Assessment; Risk Factors; Stroke; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51-0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40-0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44-1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78-2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13-2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10-2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombosis; Venous Thrombosis; Vitamin K

There is still a paucity of data on the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) in the prevention of left atrial thrombus (LAT) formation before cardioversion or catheter ablation. To assess the efficacy of NOACs in the prevention of LAT in patients with non-valvular atrial fibrillation (NVAF) compared with vitamin K antagonists (VKAs), we conducted a meta-analysis.. We searched PubMed, Embase, and the Cochrane Library databases. For meta-analysis, dichotomous variables were analyzed by using the odds ratios (OR) computed using the Mantel Haenszel method (random models). All results were reported with 95% confidence intervals (CI).. A total of 13 studies (one randomized controlled investigation and 12 observational studies) were included in the meta-analysis. There was no statistically significant difference between the NOACs and VKAs groups with respect to the odds of LAT/LAAT formations (OR 0.79; 95% CI: 0.52-1.21; P = .29; (I2 = 14%).. NOACs were as effective as VKAs in the prevention of LAT/LAAT formation in patients with NVAF. Though patients on NOACs therapy showed a lower incidence of LAT/LAAT formation compared with VKAs, it was not significant (P = .29).

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Heart Atria; Heart Diseases; Humans; Thrombosis; Vitamin K

Thromboembolism (TE) is a well-recognized complication of pediatric cancer and can lead to mortality and excess morbidity. There is conflicting evidence about the effectiveness and safety of thromboprophylaxis in children. We conducted a systematic literature review and network meta-analysis of primary pharmacological thromboprophylaxis in children and adolescents (0-21 years) with cancer. The primary outcomes were objectively proven TE and major bleeding. The network meta-analysis included comparisons of multiple alternatives simultaneously: antithrombin (AT) replacement, low molecular weight heparin (LMWH), vitamin K antagonists (VKAs), and standard of care (SOC) defined as no thromboprophylaxis or low-dose heparin for catheter patency. Six articles describing 1,318 patients were included (mean age: 6.7 years, 56.7% male). Acute lymphoblastic leukemia was the underlying diagnosis in 97.5% of patients. All studies were considered at moderate or high risk of bias. LMWH was the only agent associated with lower odds of TE compared with SOC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.06-0.81). No statistically significant difference was detected between other thromboprophylaxis modalities and SOC. Tau

Topics: Adolescent; Anticoagulants; Antithrombins; Child; Child, Preschool; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infant; Infant, Newborn; Male; Neoplasms; Network Meta-Analysis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thromboembolism; Thrombosis; Vitamin K; Young Adult

Cancer is associated with an increased risk of venous thromboembolism of four to sixfold. Cancer-related interventions such as chemotherapy, hormonal therapy and indwelling central venous catheters also increase the risk of venous thromboembolism. Low molecular weight heparin for at least 3-6 months is the current standard of care for the treatment of cancer associated venous thromboembolism. Anticoagulation should be continued as long as the cancer is active. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In the randomized controlled trials comparing direct oral anticoagulants with vitamin K antagonists, the direct oral anticoagulants all provide non-inferior in prevention of thromboembolic events in patients with atrial fibrillation, for the prevention and treatment of venous thromboembolism and in acute coronary syndrome. In people with cancer, these drugs have emerged as attractive alternatives for the treatment of venous thromboembolism with the potential to overcome the limitations of low molecular weight heparin. Randomized controlled studies comparing direct oral anticoagulants to low molecular weight heparin in cancer patients are still limited and direct oral anticoagulants are not recommended for the treatment of cancer associated venous thromboembolism yet. However, new emerging data are supporting the use of direct oral anticoagulants in cancer-associated thrombosis. Here, we review recent data on the evidence related to the efficacy and safety of direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer.

Topics: Anticoagulants; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K

To provide information on the pathogenesis, clinical features, diagnosis, and treatment of calciphylaxis.. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.. After participating in this educational activity, the participant should be better able to:1. Recognize the pathogenesis and clinical features of and risk factors for calciphylaxis.2. Explain the diagnosis and management of a patient with calciphylaxis.. Calciphylaxis is a cutaneous ischemic infarct caused by total occlusion of blood vessels initiated by vascular calcification. Until recently, treatments have been limited to controlling its risk factors and optimizing wound care. However, recent advances in clinical understanding of the mechanism of calciphylaxis have identified promising potential therapeutic targets. This article is a narrative review summarizing the clinical features, diagnosis, pathogenesis, and treatment of calciphylaxis.

Topics: Calciphylaxis; Chelating Agents; Humans; Kidney Failure, Chronic; Kidney Transplantation; Pain Management; Renal Dialysis; Risk Factors; Thiosulfates; Thrombosis; Vascular Calcification; Vitamin K; Vitamin K Deficiency; Wound Healing

The recent emergence of 'non-VKA' oral anticoagulants may have led to some forgetting that vitamin K antagonists (VKA) are by far the most widely prescribed oral anticoagulants worldwide. Consequently, we decided to summarize the information available on them. This paper presents the problems facing emergency physicians confronted with patients on VKAs in 10 points, from pharmacological data to emergency management. Vitamin K antagonists remain preferable in many situations including in the elderly, in patients with extreme body weights, severe chronic kidney or liver disease or valvular heart disease, and in patients taking VKAs with well-controlled international normalized ratios (INRs). Given the way VKAs work, a stable anticoagulant state can only be achieved at the earliest 5 days after starting therapy. The induction phase of VKA treatment is associated with the highest risk of bleeding; validated algorithms based on INR values have to be followed. VKA asymptomatic overdoses and 'non-severe' hemorrhage are managed by omitting a dose or stopping treatment plus administering vitamin K depending on the INR. Major bleeding is managed using a VKA reversal strategy. A prothrombin complex concentrate infusion plus vitamin K is preferred to rapidly achieve an INR of up to 1.5 and maintain a normal coagulation profile. The INR must be measured 30 min after the infusion. Before an invasive procedure, if an INR of less than 1.5 (<1.3 in neurosurgery) is required, it can be achieved by combining prothrombin complex concentrate and vitamin K. A well-codified strategy is essential for managing patients requiring emergency invasive procedures or presenting bleeding complications.

Topics: Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Emergencies; Emergency Medicine; Emergency Service, Hospital; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Patient Safety; Primary Prevention; Risk Assessment; Sensitivity and Specificity; Thrombosis; Vitamin K

Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed.

Topics: Brain Ischemia; Female; Hemorrhage; Hemostasis; Humans; Infant, Newborn; Infant, Premature; Male; Stroke; Thrombosis; Vitamin K; von Willebrand Factor

Arterial thrombosis is increasingly recognized in children and is mostly related to the presence of an arterial catheter or an ischemic stroke. Treatment of children with arterial thrombosis varies widely and consists on the administration of the common available anticoagulant und antiplatelet drugs. No evidence-based guidelines are available so far to prefer one treatment approach to another. Data in adults indicate that understanding the pathomechanism and composition of arterial thrombosis is crucial for choosing the most efficient and safe antithrombotic drug. This review will briefly summarize new insights on the pathomechanism and composition of arterial thrombosis in adults and describe available antithrombotic treatment modalities currently used n children.

Topics: Adult; Antithrombins; Child; Fibrinolytic Agents; Heparin; Humans; Platelet Aggregation Inhibitors; Thrombectomy; Thrombosis; Vitamin K

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Blood Coagulation; Cardiac Surgical Procedures; Cardiology; Child; Coronary Artery Bypass; Drug Administration Schedule; Evidence-Based Medicine; Fibrinolytic Agents; Heart Valve Diseases; Heart-Assist Devices; Hemorrhage; Hemostasis; Heparin; Humans; Inflammation; Intraoperative Period; Perioperative Period; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Protamines; Risk; Thrombolytic Therapy; Thrombosis; Vitamin K

To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

To assess the frequency of left atrium/left atrial appendage (LA/LAA) thrombus under treatment with non-vitamin K oral anticoagulants (NOACs) in comparison with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (AF).. PubMed, Web of Science™, EMBASE and the Cochrane Library databases were searched for studies comparing NOACs with VKAs in AF patients who underwent diagnostic transoesophageal echocardiography (TEE).. The findings of this meta-analysis suggest that NOACs are similar to VKAs regarding the frequency of LA/LAA thrombus in patients with AF. An unknown number of patients in the original studies did not receive sufficient anticoagulation for at least 3 weeks prior to TEE examination, and therefore the present results should be interpreted with caution. Systematic review registration- http://www.crd.york.ac.uk/PROSPERO . Unique identifier: PROSPERO CRD42017059293.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Heart Atria; Humans; PubMed; Thrombosis; Vitamin K

Predicting the clinical consequences of anticoagulant therapy by identifying gene variants could help in the risk assessment of thrombosis or bleeding before and after surgery and may result in choosing more beneficial therapy. This work provides an overview of pharmacogenetic data of commonly used anticoagulant medication. The review focuses on polymorphisms influencing the efficacy and safety of the parenteral and oral anticoagulants. There is evidence that heparin resistance and heparin-induced thrombocytopenia could be genetically determined but it does not mean that the risk of bleeding or thromboembolism is related to mutations in general. CYP2C9 and VKORC1 polymorphisms are essential determinants in the genotype-guided dosing of warfarin and may distinguish patients who would benefit from switching to direct oral anticoagulants (DOACs). Further multi-ethnic studies associating genes of enzymes metabolizing DOACs with primary clinical endpoints are necessary. Pharmacogenetics-based dosing of anticoagulant medication should point towards the subpopulation of patients.

Topics: Anticoagulants; Genotype; Hemorrhage; Heparin; Humans; Thrombosis; Vitamin K; Warfarin

Fibrin constitutes a major protein component of intravascular thrombi in all locations. Fibrin formation and its functions are essential for physiological hemostasis and the pathologic thrombosis. Formation of dense fibrin networks which are relatively resistant to lysis is observed in patients with venous or arterial thromboembolism, including myocardial infarction, ischemic stroke and venous thromboembolism. Measures of clot characteristics, in particular clot permeability and clot lysis time, may predict arterial and venous recurrent thromboembolic events. Medications, including vitamin K antagonists (VKA), direct oral anticoagulants (DOAC), and parenteral direct or indirect thrombin or activated factor X inhibitors increase clot permeability, reflecting fibrin network density, in association with enhanced efficiency of fibrinolysis. These effects are only in part related to decreased thrombin generation. There is evidence that aspirin can also favorably alter fibrin clot properties probably through acetylation of fibrinogen. No such effects were observed for P2Y

Topics: Anticoagulants; Aspirin; Fibrin; Fibrinolytic Agents; Humans; Purinergic P2Y Receptor Antagonists; Thrombosis; Vitamin K

Vitamin K-dependent clotting factors are commonly divided into prohemorrhagic (FII, FVII, FIX, and FX) and antithrombotic (protein C and protein S). Furthermore, another protein (protein Z) does not seem strictly correlated with blood clotting. As a consequence of this assumption, vitamin K-dependent defects were considered as hemorrhagic or thrombotic disorders. Recent clinical observations, and especially, recent advances in molecular biology investigations, have demonstrated that this was incorrect. In 2009, it was demonstrated that the mutation Arg338Leu in exon 8 of FIX was associated with the appearance of a thrombophilic state and venous thrombosis. The defect was characterized by a 10-fold increased activity in FIX activity, while FIX antigen was only slightly increased (FIX Padua). On the other hand, it was noted on clinical grounds that the thrombosis, mainly venous, was present in about 2% to 3% of patients with FVII deficiency. It was subsequently demonstrated that 2 mutations in FVII, namely, Arg304Gln and Ala294Val, were particularly affected. Both these mutations are type 2 defects, namely, they show low activity but normal or near-normal FVII antigen. More recently, in 2011-2012, it was noted that prothrombin defects due to mutations of Arg596 to Leu, Gln, or Trp in exon 15 cause the appearance of a dysprothrombinemia that shows no bleeding tendency but instead a prothrombotic state with venous thrombosis. On the contrary, no abnormality of protein C or protein S has been shown to be associated with bleeding rather than with thrombosis. These studies have considerably widened the spectrum and significance of blood coagulation studies.

Topics: Blood Coagulation Factors; Hemorrhage; Humans; Mutation; Thrombosis; Vitamin K

Antiphospholipid syndrome (APS), heparin-induced thrombocytopenia, and paroxysmal nocturnal hemoglobinuria are 3 acquired thrombophilias that carry a high risk of venous and arterial thromboembolism. Management of these conditions has largely included anticoagulation with a vitamin K antagonist after an initial period of a parenteral anticoagulant, for as long as the thrombotic risk is still present. The available evidence for the use of direct oral anticoagulants (DOACs) is limited and primarily consists of case series and cohort studies, which are summarized in this chapter. Randomized trials evaluating DOACs in patients with APS are reviewed. Further research is needed prior to widely adopting DOACs for use in these high-risk acquired thrombophilias; however, there may be selected low-risk subgroups where DOAC use is possible after careful consideration and patient discussion.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Disease Management; Hemoglobinuria, Paroxysmal; Heparin; Humans; Thrombocytopenia; Thrombophilia; Thrombosis; Vitamin K

To provide an up-to-date review of the available evidence regarding management of elderly patients after transcatheter aortic valve replacement (TAVR).. A PubMed search of articles published (September 1969-December 2016) was done using a combination of the following words: aortic valve stenosis, geriatric, elderly, transcatheter aortic valve replacement, surgical aortic valve replacement, transcatheter aortic valve implantation (TAVI), and dual antiplatelet therapy.. Relevant original research, review articles, and guidelines were assessed for the management of elderly patients after TAVR. References from the above literature were also evaluated. Articles were selected for inclusion based on relevance to the topic, detailed methods, and complete results.. Aortic valve stenosis is common in the geriatric population. While patients were historically treated with surgical aortic valve replacement (AVR), more patients are now undergoing TAVR. This article reviews the current literature regarding outcomes and pharmacotherapy between surgical and TAVR in the elderly population.. Appropriate management of pharmacotherapy after surgical or TAVR can help improve outcomes in elderly patients, and pharmacists can provide guidance regarding evidence-based therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Fibrinolytic Agents; Hematologic Agents; Humans; International Normalized Ratio; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thrombosis; Transcatheter Aortic Valve Replacement; Vitamin K

Thrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90 % subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

Topics: Anticoagulants; Antidotes; Coronary Artery Disease; Drug Discovery; Factor XI; Factor XII; Heart Failure; Heparin; Humans; Peripheral Arterial Disease; Stroke; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)] are at high risk of bleeding events (both non-major and major clinically relevant bleeding). While anticoagulation reduces the risk of thromboembolic events, the co-existing bleeding risk and the fact that the most commonly used anticoagulation agents are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin inhibitor dabigatran. In this review, we discuss the complex challenges and the practical considerations associated with the management of anticoagulation treatment in patients with CKD, with a special focus on DOACs.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Heparin; Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis; Vitamin K

Cancer associated thrombosis (CAT) is a frequent complication among cancer patients. It is associated with increased morbidity, mortality, and psychological burden. Areas covered: Low-molecular-weight heparin monotherapy for the initial 6 months is considered the standard of care for the acute and long-term management of CAT. For patients at high risk of recurrent CAT (e.g. active cancer or still undergoing anticancer therapy) beyond the initial 6 months of treatment, continuation of anticoagulation therapy for secondary prevention is usually recommended. The management of anticoagulation therapy is more challenging in patients with cancer. Cancer patients are more likely to have recurrent events despite anticoagulation, thrombocytopenia due to their chemotherapy regimens or have incidental pulmonary embolism diagnosed on their staging imaging. Expert commentary: We will review expert consensuses and opinions in order to guide clinicians on how to tailor the management of CAT in these special circumstances.

Topics: Anticoagulants; Disease Management; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Secondary Prevention; Thrombocytopenia; Thrombosis; Time Factors; Vitamin K

Cancer-associated venous thromboembolism (VTE) is primarily treated with low-molecular weight heparin (LMWH), a strategy based on studies showing it to be superior to the vitamin K antagonist (VKA) warfarin for preventing VTE recurrence. Subsequent analyses suggest that the magnitude of this benefit might be less than previously determined. Neither patient-focused measures of utility nor the costs of each strategy have been evaluated in the current treatment era.. This is a cost-effectiveness analysis of VKA and LMWH for the treatment of cancer-associated thrombosis through use of a microsimulation model of outcomes for competing anticoagulation management strategies from a 2014 United States societal perspective.. LMWH therapy added 0.27 QALYs relative to VKA treatment with an ICER of $217,007. One-way sensitivity analysis evaluating the utility of LMWH revealed that VKA was always the preferred strategy at a willingness to pay (WTP) threshold of $100,000 per QALY. Limitations include that the model incorporates a low VKA time in therapeutic range (TTR) and that the TTR in some centers may be higher thereby increasing the cost-effectiveness of the VKA strategy. Utilities for anticoagulation strategies were not derived from cancer patients, and preference is known to vary depending on how anticoagulation method is integrated with cancer treatment.. Our findings suggest that compared to LMWH, warfarin is a more cost-effective strategy to treat cancer-associated VTE. Although LMWH is associated with a modest increase in life expectancy, this increase comes at significant cost.

Topics: Anticoagulants; Cost-Benefit Analysis; Heparin, Low-Molecular-Weight; Humans; Markov Chains; Neoplasms; Quality-Adjusted Life Years; Thrombosis; Vitamin K

The relative bleeding risk of aspirin versus vitamin K antagonists (VKA) is unclear. Most of previous meta-analyses included trials with target INR for VKA therapy far beyond usually recommended range (2-3). The aim of this study was to compare the bleeding risk of aspirin and VKA, as indicated by the aggregate body of clinical evidence including data from the recently published WARCEF trial.. In this meta-analysis we included randomized controlled trials that compared aspirin to VKA (1.4

Topics: Aspirin; Global Health; Hemorrhage; Humans; Incidence; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Thrombosis; Vitamin K

In the clinical context of end-stage renal disease (ESRD), thrombosis and bleeding risks are simultaneously increased and may have devastating consequences. While anticoagulant and antiplatelet drugs are indispensable for the prevention of thromboembolic events, the significantly higher bleeding risk makes their handling extremely complicated. In ESRD, they are frequently administered for a wide array of conditions. For example, atrial fibrillation is quite common in ESRD and warrants the use of anticoagulants like warfarin. Unfractionated heparin and low molecular weight heparins are typically used for clotting prevention in the hemodialysis extracorporeal circuit. The antithrombotics use dilemma has worsened because ESRD patients have been excluded from major clinical trials that defined standard indications, contraindications and optimal management of these medications. That limits our knowledge and results in that the process of decision-making depends on weaker data. Besides the substantial bleeding risk, warfarin may also increase cardiovascular risk because it is implicated in the pathogenesis of vascular calcifications in ESRD. The present article attempts to offer a comprehensive overview of practical considerations for the use of the most common antithrombotic medications in ESRD linking them, at the same time, to the best available evidence from randomized controlled trials and observational studies.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Platelet Aggregation Inhibitors; Renal Dialysis; Thrombosis; Vitamin K

Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

Topics: Administration, Oral; Anticoagulants; Asian; Black or African American; Disease Management; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Neoplasms; Polysaccharides; Prevalence; Quality of Life; Recurrence; Risk Factors; Taiwan; Thrombosis; United States; Venous Thromboembolism; Vitamin K; Warfarin; White People

The current treatment of thrombotic APS patients includes long-term anticoagulation with oral vitamin K antagonists (VKAs), with warfarin being the one most commonly used. However, the use of VKAs can be challenging, especially in patients with APS. VKAs monitoring in patients with aPL is complicated by the heterogeneous responsiveness to LAs of reagents used in the International Normalized Ratio test, potentially resulting in instability of anticoagulation. For decades, VKAs were the only available oral anticoagulants. However, non-VKA oral anticoagulants, including a direct thrombin inhibitor (dabigatran etexilate) and direct anti-Xa inhibitors (rivaroxaban, apixaban and edoxaban), are currently available. The use of these agents may represent a major step forward since, unlike VKAs, they have few reported drug interactions and they do not interact with food or alcohol intake, thereby resulting in more stable anticoagulant intensity. Most importantly, monitoring their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this review, we discuss the clinical and laboratory aspects of non-VKA oral anticoagulants, focusing on the available evidence regarding their use in patients with APS.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Antithrombins; Breast Feeding; Factor Xa Inhibitors; Female; Food-Drug Interactions; Hemorrhage; Humans; Kidney Diseases; Liver Diseases; Lupus Coagulation Inhibitor; Pregnancy; Pregnancy Complications; Thrombosis; Vitamin K

The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient-related and procedure-related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non-valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aortic Valve; Atrial Fibrillation; Elective Surgical Procedures; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Perioperative Care; Phenprocoumon; Prothrombin; Randomized Controlled Trials as Topic; Societies, Medical; Thromboembolism; Thrombosis; United States; Vitamin K; Warfarin

While evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain.. To determine the optimal timing of VKA re-initiation and its associated clinical outcomes.. We performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence.. 23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%-25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%-17%) and 12% (95% CI, 5%-23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with VKA resumption at 3days to 0% with resumption at 16days.. Among patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4-7days might be an ideal time with least risk of thrombosis or ICH recurrence.

Topics: Anticoagulants; Heart Valve Prosthesis; Humans; Intracranial Hemorrhages; Thrombosis; Vitamin K; Warfarin

Intracerebral hemorrhage (ICH) in patients with oral anticoagulation therapy is an increasingly prevalent problem in large part due to the aging population and the increased use of anticoagulants for patients at high risk of thrombosis. Warfarin has been virtually the only outpatient anticoagulant choice until fairly recently. The development of subcutaneously injected heparinoids, and more recently, of direct thrombin inhibitors, has made the treatment and prognostication of ICH in anticoagulated patients more difficult. In this review, we will review the current state of diagnosis, prognostication, and treatment for patients with this often-devastating type of bleeding. We will focus on warfarin therapy, because the preponderance of evidence comes from studies of warfarin treatment. Where there is evidence, we will contrast warfarin with some of the newer treatment modalities. We review the evidence of the 4 major reversal agents for warfarin, vitamin K, prothrombin complex concentrates, activated factor VII, and fresh frozen plasma as well as rational treatment choices. We offer possible treatments for the newer anticoagulants based on the limited evidence available. Finally, we review recommendations from the major societies and studies that support early and aggressive therapies in intensive care units with dedicated neurological specialists.

Topics: Administration, Oral; Age Factors; Anticoagulants; Blood Coagulation Factors; Cerebral Hemorrhage; Critical Care; Factor VIIa; Humans; Plasma; Thrombosis; Tomography, X-Ray Computed; Vitamin K; Warfarin

Insomnia is an important adverse event of mechanical thromboprophylaxis. This sleep disorder has been reported as one of the commonest adverse events of the new oral anti-Xa anticoagulant darexaban, with similar rates to mechanical thromboprophylaxis in a randomized controlled trial (RCT). However, the perceived effect could have been biased because it was an open-label RCT. Therefore, we aimed to review the incidence of insomnia with non-vitamin K antagonist oral anticoagulants (NOACs).. We performed a systematic review and meta-analysis of Phase III RCTs. Electronic databases MEDLINE and CENTRAL (inception to September 2013) were searched as well as review articles and references of included studies. We included phase III RCTs which compared NOACs with any other control group. Data were analyzed and pooled to estimate risk ratio (RR) with 95% confidence intervals (95%CI) for insomnia using inverse variance method. Statistical heterogeneity was evaluated with I(2) test.. We included seven studies (two apixaban RCTs, two dabigatran RCTs, one darexaban RCTs, and two rivaroxaban RCTs), enrolling a total of 23,023 patients. Overall, NOACs were not associated to an increased risk of insomnia: RR 0.94 (95%CI 0.83-1.08; I(2) = 0%). In blinded studies (six studies), NOACs also did not show increased risk of insomnia (RR 0.94, 95%CI 0.83-1.08; I(2) = 0%). Results were similar irrespective of the comparators.. NOACs (apixaban, dabigatran, darexaban, rivaroxaban) did not show increased risk of insomnia. Results according to study design (blinded vs. open-label trials) overlap the main analysis.

Topics: Administration, Oral; Anticoagulants; Azepines; Benzamides; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Thrombosis; Vitamin K

One of the major advances in the management of thrombosis is arguably the introduction of the new non-vitamin K antagonist oral anticoagulants (NOACs). These are small molecules, designed to directly inhibit specific steps in the coagulation pathway, with dabigatran (Pradaxa), inhibiting thrombin and rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Lixiana), and betrixaban being factor Xa inhibitors. They have several advantages over vitamin K antagonists such as warfarin, with more predictable bioavailability, fewer drug interactions, and improved safety, especially intracranial hemorrhage. Yet, since their debut, several issues have arisen with their increasing usage, with concerns over monitoring and reversal, being predominant. Issues addressed in this article include their efficacy, bleeding risk, and the recognition of a vulnerable population where monitoring is needed. The current approach to reversing the drug action is updated. The change in the approach to future drug design is also discussed.

Topics: Administration, Oral; Anticoagulants; Drug Monitoring; Humans; Inactivation, Metabolic; Thrombosis; Vitamin K

Several new anticoagulants have entered the clinical arena or are under clinical development. These drugs include indirect (fondaparinux) and direct oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), and the direct thrombin inhibitor dabigatran. Especially the oral direct FXa and FIIa inhibitors overcome many of the shortcomings of heparins and vitamin K antagonists (VKAs). They are administered orally at a fixed dose; regular monitoring is not necessary; interaction with other drugs or nutrition occur less than with VKAs and they are at least as effective as VKAs for most indications tested. They are associated with about 50 % less intracranial bleeding than VKAs. Nevertheless, they are still associated with bleeding complications. Bleeding can occur spontaneously or as a result of trauma or urgent surgery. In such situations rapid reversal of the anticoagulant effect is highly desirable. For unfractionated heparin protamine, and for VKAs prothrombin complex concentrates are available as specific antidotes. Under clinical development are: for the direct and indirect FXa inhibitors a modified recombinant FXa (andexanet alpha), which lacks enzymatic activity; and for dabigatran a Fab fragment of a monoclonal antibody (idarucizumab). In addition a small molecule (aripazine) has entered phase I clinical trials, which seems to inhibit nearly all anticoagulants but VKAs and argatroban. This review summarises the current options and strategies in development to antagonise anticoagulants with a focus on the status of the development of antidotes for the oral direct FXa and FIIa inhibitors.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antithrombins; Benzamides; Clinical Trials as Topic; Dabigatran; Factor Xa; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Hemostatics; Heparin; Humans; Infusions, Parenteral; Intracranial Hemorrhages; Polysaccharides; Protamines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; Thrombosis; Vitamin K

The major practical advantage of the direct oral anticoagulants (DOACs), comprising the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, over vitamin K antagonists is their fixed dosing without the need for laboratory monitoring. With the recent, rapid introduction of the DOACs for the treatment of acute venous thromboembolism (VTE), clinicians are now faced with various questions regarding the efficacy and safety of these compounds overall and in specific high-risk populations. The collective evidence from 6 large clinical trials involving 27,000 patients has demonstrated that DOACs are as effective as vitamin K antagonists (VKA) in preventing recurrent VTE while being associated with a significantly lower risk of major bleeding. These findings are consistent in subgroups of patients with pulmonary embolism, the elderly, and those patients with a high body weight or moderate renal insufficiency, making these agents suitable for a broad spectrum of patients with VTE. DOACs are also an attractive treatment option in patients with VTE and concomitant cancer, thrombotic antiphospholipid syndrome, or heparin-induced thrombocytopenia, but the currently available clinical data is insufficient to make evidence-based recommendations on the use of DOACs in these settings. Several studies evaluating the efficacy and safety of DOACs in these high-risk populations are underway.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Clinical Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Pulmonary Embolism; Recurrence; Renal Insufficiency; Risk; Thrombin; Thrombocytopenia; Thrombosis; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients.. Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Blood Coagulation Tests; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; International Normalized Ratio; Liver Failure; Metabolic Clearance Rate; Morpholines; Perioperative Care; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Vitamin K

The use of new oral anticoagulants (NOACs) in patients with impaired renal function has raised major concerns, in particular the possibility of an increased risk of bleeding due to accumulation. The aims of this work were to assess the safety of NOACs in patients with renal failure and describe the relationship between clinical events and drug renal excretion magnitude.. All phase III trials comparing NOACs with vitamin K antagonists (VKAs) in patients with estimated glomerular filtration (eGFR) rate < 50 mL min(-1) were eligible. The main safety and efficacy outcomes were major bleeding and thrombosis. A meta-regression was performed to estimate the correlation between the treatment effect estimate and the percentage of renal excretion.. Nine studies (12 272 patients) were included. A significantly greater relative reduction in major bleeding was seen for NOACs with renal excretion <50% (RR, 0.61; CI, 0.51-0.74) than for those with high renal excretion (RR, 0.96; CI, 0.85-1.07) (interaction test, P < 0.0001). A linear relationship between the relative risk of major bleeding and the magnitude of renal excretion was found by meta-regression (R(2)  = 0.66, P = 0.03). For thrombosis, a greater treatment effect of NOA vs. INR-adjusted VKA was observed in patients with eGFR < 50 mL min(-1) (RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal excretion was found.. New oral anticoagulants were at least as effective as VKAs, with reduced risks of major bleeding and thrombosis in patients with eGFR < 50 mL min(-1) . The renal excretion of these new drugs seemed to modify the safety profile, contrary to the efficacy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Glomerular Filtration Rate; Hemorrhage; Humans; Renal Insufficiency; Thrombosis; Treatment Outcome; Venous Thromboembolism; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Embolism; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin

Cardiovascular disease remains a major cause of morbidity and mortality in developed countries. New treatments, in the form of novel oral anticoagulants (NOAC) that reduce thrombotic risk are now available for patients with atrial fibrillation (AF) or acute coronary syndrome (ACS). Warfarin has been the cornerstone of thromboprophylaxis in patients with AF, but treatment is cumbersome, inconvenient and often unreliable, with fluctuating time in therapeutic range. Thrombotic events also continue to occur in a significant number of ACS patients despite antiplatelet therapy. Thus there is an unfilled need to reduce thrombotic events in ACS and AF patients. NOAC comprise direct factor Xa inhibitors (apixaban, rivaroxaban, darexaban, edoxaban), direct thrombin inhibitors (dabigatran) and PAR-1 antagonists (vorapaxar, atopaxar). In this review, we compare and contrast NOACs and review their individual and specific clinical trial database in ACS and AF. In the setting of ACS, the role of NOAC is unclear, as any reduction in ischemic events appears to be offset by hemorrhagic risk. However, NOAC have a definite place in the treatment of patients with non-valvular AF, where they are at least as effective, if not superior to warfarin.

Topics: Acute Coronary Syndrome; Administration, Oral; Animals; Anticoagulants; Antithrombins; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Thrombosis; Vitamin K

The main purpose of anticoagulants is to diminish fibrin formation, thereby decreasing the risk of venous or arterial thrombosis. Vitamin K antagonist have been used for many decades in order to achieve reduced thrombotic risk, despite major drawbacks of this class of drugs such as cumbersome dossing and monitoring of anticoagulant status. To overcome these drawbacks of VKA, new classes of anticoagulants have been developed including oral anticoagulants for direct inhibition of either thrombin or factor Xa, which can be administrated in a fixed dose without monitoring. Coagulation factors can activate cellular protease-activated receptors, thereby inducing cellular processes as inflammation, apoptosis, migration, and fibrosis. Therefore, inhibition of coagulation proteases not only attenuates fibrin formation, but may also influence pathophysiological processes like vascular calcification and atherosclerosis. Animal models revealed that VKA therapy induced both intima and media calcification and accelerated plaque vulnerability, whereas specific and direct inhibition of thrombin or factor Xa attenuated atherosclerosis. In this review we provide an overview of old and new oral anticoagulants, as well discuss potential pleiotropic effects with regard to calcification and atherosclerosis. Although translation from animal model to clinical patients seems difficult at first sight, effort should be made to fully understand the clinical implications of long-term oral anticoagulant therapy on vascular side effects.

Topics: Animals; Anticoagulants; Antithrombins; Atherosclerosis; Atrial Fibrillation; Blood Coagulation Factors; Calcinosis; Coumarins; Disease Models, Animal; Disease Progression; Drug Monitoring; Enzyme Activation; Factor Xa Inhibitors; Hemorrhage; Humans; Practice Guidelines as Topic; Protease Inhibitors; Randomized Controlled Trials as Topic; Receptors, Proteinase-Activated; Stroke; Thrombosis; Vitamin K

Disadvantages with traditional anticoagulants (vitamin K antagonists and heparinoids) have led to the development on non-vitamin K antagonist oral anticoagulants (NOACs). These agents are set to replace the traditional anticoagulants in situations such as following orthopaedic surgery, in atrial fibrillation, and in the prevention and treatment of venous thromboembolism. Although superior to vitamin K antagonists and heparinoids in several aspects, NOACs retain the ability to cause haemorrhage and, despite claims to the contrary, may need monitoring. This review aims to summarise key aspects of the NOACs of relevance to the laboratory.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Dose-Response Relationship, Drug; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombosis; Treatment Outcome; Vitamin K

Long-term anticoagulation is required in all patients with mechanical prosthetic heart valves to prevent complications with valve thrombosis and valve failure or systemic thromboembolism. The prothrombotic environment of pregnancy further increases the risks of these complications. Anticoagulant choices for pregnant women include oral vitamin K antagonists such as warfarin, or heparin - either unfractionated heparin (UFH) or low molecular weight heparin (LMWH). None of the options is without risk for the mother or her baby. Warfarin crosses the placenta and is associated with warfarin embryopathy and fetopathy but is very effective at preventing thromboembolic complications. The dose of warfarin may play a role in the risk of some, but not all fetal complications. Heparin does not cross the placenta but is less effective at preventing thrombosis and LMWH may be more effective than UFH. The optimal dose and target anti-Xa levels for LMWH have not been established. Measurement of trough anti-Xa levels in addition to peak anti-Xa levels may be important.

Topics: Anticoagulants; Cohort Studies; Factor Xa; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Heparin, Low-Molecular-Weight; Humans; Maternal Exposure; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Outcome; Risk; Thromboembolism; Thrombosis; Vitamin K; Warfarin

Until recently, it was widely accepted that patients with cirrhosis have a bleeding tendency related to the changes in the hemostatic system that occur as a consequence of the disease. However, it has now been well established that patients with cirrhosis are at risk for both bleeding and thrombotic complications. These thrombotic complications include portal vein thrombosis, deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in patients with cirrhosis have been used only minimally in the past due to the perceived bleeding risk. As the thrombotic complications and the necessity of antithrombotic treatment in these patients are increasingly recognized, the use of antithrombotic drugs in this population is likely increasing. Moreover, given the rising incidence of fatty liver disease and generally longer survival times of patients with chronic liver diseases, it would be reasonable to presume that some of these thrombotic complications may be increasing in incidence over time. In this review, we will outline the indications for antithrombotic treatment in patients with cirrhosis. Furthermore, we will discuss the available antithrombotic drugs and indicate possible applications, advantages, and caveats. Since for many of these drugs very little experience in patients with cirrhosis exists, these data are essential in the design of future clinical and laboratory studies on mechanisms, efficacy, and safety of the various antithrombotic strategies in these patients.

Topics: Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Disease Progression; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Liver Cirrhosis; Morpholines; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Thromboembolic complications are among the most important extrarenal consequences of nephrotic syndrome (NS). In addition to deep vein thrombosis in the legs and pulmonary embolism, NS is very frequently accompanied by renal vein thrombosis. Due to enhanced procoagulatory and antifibrinolytic potential and reduced anticoagulatory potential, multifactor disruption of hemostatic equilibrium leads to hypercoagulability in NS patients, which is aggravated by an increase in blood viscosity and endothelial dysfunction. Circulating antibodies against α-enolase, a plasmin(ogen)-binding protein, and the possibility of certain molecules being renally eliminated in specific manner are discussed as reasons for the particular frequency of thromboembolic complications in patients with idiopathic membranous nephropathy. Serum albumin concentration is an indicator for the risk of thrombosis in NS patients. When applying the current KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for glomerulonephritis to NS patients with a serum albumin concentration of less than 25 g/l and at least one additional thrombogenic risk factor, primary prophylactic anticoagulation ("conditioned prophylaxis") with an orally administered vitamin K antagonist (target INR 2-3) is recommended as long as the serum albumin concentration is less than 30 g/l.

Topics: Anticoagulants; Autoantibodies; Blood Viscosity; Endothelium, Vascular; Hemostasis; Humans; Nephrotic Syndrome; Pulmonary Embolism; Renal Veins; Risk Factors; Serum Albumin; Thromboembolism; Thrombosis; Venous Thrombosis; Vitamin K

Given the rising incidence of thrombotic complications in paediatric patients, understanding of the pharmacologic behaviour of anticoagulant drugs in children has gained importance. Significant developmental differences between children and adults in the haemostatic system and pharmacologic parameters for individual drugs highlight potentially unique aspects of anticoagulant pharmacology in this special and vulnerable population. This review focuses on pharmacologic information relevant to the dosing of unfractionated heparin, low molecular weight heparin, warfarin, bivalirudin, argatroban and fondaparinux in paediatric patients. The bulk of clinical experience with paediatric anticoagulation rests with the first three of these agents, each of which requires higher bodyweight-based dosing for the youngest patients, compared with adults, in order to achieve comparable pharmacodynamic effects, likely related to an inverse correlation between age and bodyweight-normalized clearance of these drugs. Whether extrapolation of therapeutic ranges targeted for adult patients prescribed these agents is valid for children, however, is unknown and a high priority for future research. Novel oral anticoagulants, such as dabigatran, rivaroxaban and apixaban, hold promise for future use in paediatrics but require further pharmacologic study in infants, children and adolescents.

Topics: Anticoagulants; Child; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombosis; Vitamin K

The eighth edition (AT8) of the American College of Chest Physicians (ACCP) Antithrombotic Therapy and Prevention of Thrombosis Guideline, published in June 2008, was a comprehensive presentation of primary studies and detailed discussions of rationale for recommendations. This resulted in an approximately 900-page Chest Supplement publication. Updating the guidelines in a succinct fashion posed a formidable challenge for the ninth edition (AT9), published in February 2012. The strategy adopted for AT9 was to publish an Executive Summary of the recommendations in a 50-page document in the Chest supplement highlighting the changes, with online publication of the full version. Major innovative changes include a recognition of the value of estimating the risk reductions in symptomatic, as opposed to asymptomatic (venographically), detected venous thrombosis, using nonconflicted methodologists as topic editors, new insights into evidence, and increasing emphasis on what is known about patients' values and preferences that have served to improve this edition of the guidelines. This review provides a summary of the updates of the guidelines for anticoagulation therapy and prevention of thrombosis. The AT9 recommendations are presented with, if included, the AT8 recommendations in parenthesis for comparison purposes.

Topics: Drug Synergism; Fibrinolytic Agents; Humans; Morpholines; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Thrombosis; United States; Vitamin K

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Dosage Calculations; Drug Interactions; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombosis; Vitamin K; Warfarin

Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting γ-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.

Topics: Advisory Committees; Anticoagulants; Blood Coagulation; Cardiology; Europe; Heart Diseases; Humans; Societies, Medical; Thrombosis; Vitamin K

Monitoring of the anticoagulant effect with the International normalized ratio (INR) is essential for patients receiving vitamin K antagonists (VKAs). The majority of point of care (POC) devices for INR monitoring has shown a good precision and accuracy with results similar to those obtained in a laboratory. In many countries, INR POC devices are widely used at home by the patients for self-testing. Their use in the hospital by the clinical staff (doctor or nurses) for bedside measurement is also growing. The INR POC testing is performed using fully automated devices. Capillary blood samples are easy to obtain. In the emergency room, POC INR devices are commonly used. This improves the quality of care for patient with suspicion of VKAs overdosage. INR measurement using bedside monitors is also of great interest in care units for specific populations of patients like paediatrics or geriatrics. Moreover, bedside INR monitoring may be useful in anticoagulant clinics or when the care unit is far from a laboratory. Although the bedside INR monitors are easy to use, their implementation requires adequate training and intermittent re-evaluation of any person performing the tests to ensure reliability of results. Such equipment must comply with EN ISO 22870 standard for POC testing accreditation, under the supervision of a biologist. In order to achieve these targets, connect the instrument to the laboratory's data management system is essential.

Topics: 4-Hydroxycoumarins; Aged; Anticoagulants; Child; Equipment and Supplies; Hematologic Tests; Humans; Indenes; Monitoring, Physiologic; Point-of-Care Systems; Thromboembolism; Thrombosis; Vitamin K

Physicians are occasionally faced with difficult situations in the management of vitamin K antagonists (VKA) due to the lack of sound data available in controlled studies on certain conditions. In this review we would like to address some special but frequent conditions that can be encountered in daily clinical practice. These include the use of VKA in hemodialysis, thromboembolism in patients with liver cirrhosis and the thromboembolic risk in patients who bleed in the course of treatment with VKA. Moreover, two other conditions were examined: what the best way of expressing prothrombin time would be in patients with liver disease and how to behave when a patient treated with VKA shows a subtherapeutic INR. These topics were discussed by a panel of experts during a workshop recently held in Milan by the Italian Federation of Centres for the Diagnosis of Thrombosis and the Surveillance of Antithrombotic Therapies (FCSA). The main aim of the workshop was to provide helpful and practical advice to physicians in the daily management of VKA.

Topics: Anticoagulants; Hemorrhage; Humans; International Normalized Ratio; Italy; Liver Cirrhosis; Liver Diseases; Renal Dialysis; Risk Assessment; Thrombosis; Vitamin K; Vitamins

Since the discovery of heparin nearly a century ago, there have been large gaps in the development of anticoagulants. The discovery of warfarin was the first step toward using oral anticoagulants, but warfarin use has been associated with its own challenges from the perspectives of the prescribing physician and the patient. Warfarin, along with other coumarins, has a narrow therapeutic index, requires frequent monitoring, exhibits interindividual response variations, and is associated with several adverse effects. Frequent drug and food interactions contribute to potential safety and efficacy compromise. The indications for use of oral anticoagulants have increased, as these drugs are used not only for thrombosis management but also for cardiovascular indications, producing more challenges for oral anticoagulant use. Factor Xa and thrombin targeting has provided a rational approach to develop new oral anticoagulants with improvements over warfarin. In this review, the pharmacology of warfarin and the pharmacology of the newly developed oral anti-Xa and antithrombin agents are discussed.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Food-Drug Interactions; Hemostatics; Heparin, Low-Molecular-Weight; Humans; Pharmacogenetics; Prothrombin; Thrombin; Thrombosis; Vitamin K; Warfarin

Vitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real-world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and dose adjustment. Around half of patients receiving warfarin are within the therapeutic range, exposing them to the dangers of under-anticoagulation (i.e. thrombosis formation) or over-anticoagulation (i.e. bleeding). A new generation of OACs with improved pharmacology promises to revolutionize antithrombotic management. Rivaroxaban, apixaban (both oral direct Factor Xa inhibitors) and dabigatran (a direct thrombin inhibitor) all exhibit predictable anticoagulant responses and few drug-drug interactions and do not require routine coagulation monitoring.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Food-Drug Interactions; Hemorrhage; Humans; Thrombosis; Vitamin K

High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices.. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.. Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education.. We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied.

Topics: Administration, Oral; Decision Support Systems, Clinical; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Humans; Infusions, Intravenous; International Normalized Ratio; Long-Term Care; Patient Education as Topic; Polysaccharides; Randomized Controlled Trials as Topic; Self Care; Societies, Medical; Thrombosis; United States; Vitamin K

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke.. The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.. Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C).. Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed.

Topics: Anticoagulants; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Heparin; Humans; International Normalized Ratio; Platelet Count; Risk Factors; Societies, Medical; Thrombocytopenia; Thromboembolism; Thrombosis; United States; Vitamin K

The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management.. We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban. The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal.. There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Evidence-Based Medicine; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Practice Guidelines as Topic; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombosis; United States; Vitamin K

Topics: Anticoagulants; Antifibrinolytic Agents; Antithrombins; Biological Availability; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Hemorrhage; Heparin; Humans; Thrombocytopenia; Thrombosis; Vitamin K

On of the most common, and serious, complications in cardiac surgery is postoperative bleeding. According to the majority of studies, between 10% and 92% of patients subjected to elective surgery require transfusions of blood products and blood derivatives. Transfusions and reinterventions are associated with longer stays in critical care units and a decrease in survival rates. There have been some important changes in the treatment of changes in haemostasis and post-surgical bleeding in the last few years, particularly with the introduction into clinical practice of working procedures backed up by clinical guidelines, as well as the appearance of new drugs. The aim of this work is to describe the main characteristics and update the use of prothrombin complexes that are currently available in Spain, with special emphasis on their use in cardiac surgery.

Topics: Anticoagulants; Blood Coagulation Factors; Blood Loss, Surgical; Blood-Borne Pathogens; Cardiac Surgical Procedures; Contraindications; Disease Transmission, Infectious; Drug Contamination; Drug Costs; Heart Diseases; Hemorrhagic Disorders; Hemostatics; Humans; Postoperative Hemorrhage; Preanesthetic Medication; Thrombophilia; Thrombosis; Vitamin K

Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach or whether a perioperative "bridge" with an alternative agent, typically a low-molecular-weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Middle Aged; Morpholines; Perioperative Care; Risk; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis; Vitamin K

Central venous catheters (CVCs) are used extensively in cancer patients for the administration of therapy and phlebotomy. An important complication of CVCs is the development of catheter-related thrombosis (CRT), which becomes symptomatic in approximately 5% of the patients. Several factors, such as insertion location and position of the catheter tip, increase the risk of CRT. Prevention of CRT with systemic anticoagulant prophylaxis has largely been ineffective. In addition, the optimal diagnostic strategy and anticoagulant treatment are unclear due to the lack of well-designed studies. The most recent American College of Chest Physicians guidelines recommend (color) Doppler ultrasound more than venography as the initial diagnostic test in patients with suspected arm thrombosis. Only if the ultrasound is negative and clinical suspicion is high is further testing with D-dimer, serial ultrasound, or venography advocated. In case of CRT, removal of the catheter is not necessary if it is functional and needed for chemotherapy. Anticoagulant treatment of CRT consists of treatment with low-molecular-weight heparin (LMWH) followed by vitamin K antagonists for at least 3 months. Whether long-term treatment with LMWH is more effective than vitamin K antagonists in cancer patients with CRT is unknown, but LMWH may be advocated following the recommendations in lower limb thrombosis and cancer. In addition, the effect of new anticoagulants in CRT has not been studied.

Topics: Anticoagulants; Antineoplastic Agents; Catheterization, Central Venous; Fibrin Fibrinogen Degradation Products; Guidelines as Topic; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Odds Ratio; Probability; Randomized Controlled Trials as Topic; Risk; Risk Factors; Societies, Medical; Thrombosis; United States; Vitamin K

Millions of patients worldwide are prescribed vitamin K antagonists for a variety of medical conditions annually. Despite widespread and long-standing experience with these medications, medical care providers are often confronted with challenging clinical situations. Vitamin K antagonists have a narrow therapeutic index secondary to intrinsic patient characteristics and extrinsic factors including a propensity for drug-drug interactions. Clinicians are required to titrate doses according to the measured international normalized ratio for each individual, balancing the risk of bleeding with preventing thrombosis. The risk of major bleeding associated with vitamin K antagonists has been reported to range from 1 to 3% per year. This narrative review will provide an overview of the most commonly used vitamin K antagonists and discuss the importance of assessing quality of anticoagulation with respect to clinical outcomes. Practical approaches to managing excessive anticoagulation, variable anticoagulation, and anticoagulation failure will be provided, drawing on evidence where applicable and expert opinion where evidence is limited.

Topics: Anticoagulants; Drug Interactions; Hemorrhage; Humans; International Normalized Ratio; Monitoring, Physiologic; Risk Factors; Thrombosis; Vitamin K; Warfarin

Vitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety. This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other "xabanes" currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making "anticoagulation bridging" unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them. Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

Topics: Anticoagulants; Coumarins; Heparin; Humans; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Platelets; Disease Susceptibility; Factor XII; Feedback, Physiological; Fibrinolysis; Hemorrhagic Disorders; Hemostasis; Hemostatic Disorders; Hemostatics; Humans; Thrombosis; Vitamin K

An increased prothrombotic state is a major risk factor for the development of heart attacks, strokes, and venous thromboembolism. Platelet activation and aggregation play an important role in determining a prothrombotic state. Although pharmaceutical agents such as aspirin, heparin, and warfarin are able to reduce prothrombotic tendency, long-term drug treatment may produce a variety of side effects, including bleeding. Diet is generally recognized to be significantly involved in modifying the individual risk for the development of thrombotic diseases, although its influence during the treatment of these disorders is probably less important. Dietary intervention has proven effective in lowering serum lipid levels, which are otherwise essential elements in the pathogenesis of cardiovascular disease. Likewise, certain dietary components have also been proven effective in decreasing platelet activation through various mechanisms and therefore may contribute to attenuating the future risk of thrombosis. This article provides an up-to-date review of the role of nutrient and nonnutrient supplements on platelet aggregation and risk of thrombosis.

Topics: Alcohol Drinking; Allium; Diet; Dietary Carbohydrates; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fibrinolytic Agents; Flavonoids; Ginkgo biloba; Humans; Methionine; Phenols; Platelet Activation; Platelet Aggregation; Polyphenols; Receptors, Calcitriol; Resveratrol; Solanum lycopersicum; Stilbenes; Thrombosis; Vitamin B Complex; Vitamin E; Vitamin K; Zingiber officinale

Peripheral arterial disease (PAD) is frequently treated by either an infrainguinal autologous (using the patient's own veins) or synthetic graft bypass. The rate of occlusion of the graft after one year is between 12% and 60%. To prevent occlusion, patients are treated with an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion. This is an update of a Cochrane review first published in 2003.. To evaluate whether antithrombotic treatment improves graft patency, limb salvage and survival in patients with chronic PAD undergoing infrainguinal bypass surgery.. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3).. Randomised, controlled trials; two review authors independently assessed the methodological quality of each trial using a standardised checklist.. Data collected included patient details, inclusion and exclusion criteria, type of graft, antithrombotic therapy, outcomes, and side effects.. A total of 14 trials were included in this review; 4970 patient results were analysed. Four trials evaluating vitamin K antagonists (VKA) versus no VKA suggested that oral anticoagulation may favour autologous venous, but not artificial, graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin (ASA) or aspirin and dipyridamole provided evidence to support a positive effect of VKA on the patency of venous but not artificial grafts. Three trials comparing low molecular weight heparin (LMWH) to unfractionated heparin (UFH) failed to demonstrate a significant difference on patency. One trial comparing LMWH with placebo found no significant improvement in graft patency over the first postoperative year in a population receiving aspirin. One trial showed an advantage for LMWH versus aspirin and dipyridamol at one year for patients undergoing limb salvage procedures. Perioperative administration of ancrod showed no greater benefit when compared to unfractionated heparin. Dextran 70 showed similar graft patency rates to LMWH but a significantly higher proportion of patients developed heart failure with dextran.. Patients undergoing infrainguinal venous graft are more likely to benefit from treatment with VKA than platelet inhibitors. Patients receiving an artificial graft benefit from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers are needed in the future to compare antithrombotic therapies with either placebo or antiplatelet therapies.

Topics: Arteriosclerosis; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Intermittent Claudication; Ischemia; Leg; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

Anticoagulant prophylaxis for preventing venous thrombembolism (VTE) is a worldwide established procedure in hip (HR) and knee replacement (KR) surgery, as well as in the treatment of femoral neck fractures (FNF). Different guidelines are available in the literature, with quite different recommendations. None of them is a multidisciplinary effort as the one presented. The Italian Society for Studies on Hemostasis and Thrombosis, the Italian Society of Orthopedics and Traumatology, the association of Orthopedic Traumatology of Italian Hospitals, together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care have set down easy and quick suggestions for VTE prophylaxis in HR and KR surgery as well as in FNF treatment. This inter-society consensus statement aims at simplifying the grading system reported in the literature, and thus at improving its proper application. Special focus is given to fragile patients, those with high bleeding risk, and on those receiving chronic antiplatelet and vitamin K antagonists treatment. A special chapter is dedicated to regional anesthesia and VTE prophylaxis.

Topics: Anesthesia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Consensus; Femoral Neck Fractures; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Patient Safety; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Risk; Stockings, Compression; Thrombosis; Venous Thromboembolism; Vitamin K

Thrombosis in children is becoming more prevalent due to increased awareness of these issues in the pediatric population and advances in medicine. Management of affected children are challenging due to differences in their hemostatic system compared with adults. Prospective, controlled trials for management/treatment of children with thrombosis are lacking. Many of the available guidelines for treatment of thrombosis in children are extrapolated from adult data and do not account for the uniqueness of the pediatric hemostatic system, although more research and data are becoming available. This review will focus on children over 1 year of age, including adolescents, looking at the etiology of thrombosis, diagnosis, management options, and any associated complications in this pediatric population.

Topics: Adolescent; Anticoagulants; Catheterization, Central Venous; Child; Child, Preschool; Factor V; Fibrinolytic Agents; Hemostasis; Heparin; Humans; Iliac Vein; Infant; Prothrombin; Pulmonary Embolism; Thrombosis; Venous Thrombosis; Vitamin K; Warfarin

Next-generation oral anticoagulants offer the potential for effective prevention and treatment of thrombosis without the need for repeated monitoring of the international normalized ratio (INR). This systematic review evaluated the costs associated with INR monitoring tests performed as part of the standard management of oral anticoagulation with vitamin K antagonists. Studies published in or after 1990 reporting the costs of INR monitoring were identified from bibliographic databases and manual searches of reference lists. Cost data were extracted and inflated to the year 2006 before purchasing power parity conversion to US dollars. A total of 29 studies reported the cost of one INR test, which was shown to range from $6.19 to $145.70. Cost estimates were based on various combinations of direct medical costs, such as healthcare contacts, equipment, laboratory tests, clerical costs (postage and stationery), telephone calls, quality control, training/education and patient transportation, and indirect costs, such as time lost from work. In conclusion, the cost of INR monitoring varied substantially between studies depending on the monitoring modality and setting, and the cost categories included. When selecting a published estimate, healthcare decision makers should ensure that the chosen estimate reflects local service provision as closely as possible.

Topics: Administration, Oral; Anticoagulants; Costs and Cost Analysis; Humans; International Normalized Ratio; Thrombosis; Vitamin K

The aim of medicinal treatment, during and after femoral and crural interventions is to prevent early or late onset arterial thrombosis of the treated vascular segments. Therefore, unfractionated heparin is administered during the intervention by an intra-arterial or intravenous approach. To avoid late onset thrombosis, administration of platelet function inhibitors is recommended. However, valid data are only available for acetylsalicylic acid (ASA). Therefore, ASA is recommended for long term medication. In several cardiological studies on stent implantation in coronary vessels the combination of ASA and clopidogrel for dual platelet inhibition has been proven to be effective. These results have been transferred to antithrombotic therapy of the lower extremities despite the lack of dedicated studies. There is no evidence for the use of vitamin K antagonists after peripheral interventions.

Topics: Administration, Oral; Anticoagulants; Arterial Occlusive Diseases; Aspirin; Clopidogrel; Drug Therapy, Combination; Heparin; Humans; Infusions, Intravenous; Ischemia; Leg; Long-Term Care; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombocytopenia; Thrombosis; Ticlopidine; Vitamin K

Different guidelines exist regarding the prevention of venous thromboembolism (VTE) in orthopedic surgery.. We aimed to compare (inter)national guidelines and analyse differences.. MEDLINE, the Cochrane Library and the internet were searched for guidelines on the prevention of VTE in orthopedic surgery. From these, we constructed a table comparing the different antithrombotic regimens during different orthopedic surgical and plaster cast treatments.. Eleven guidelines from nine different countries and one international guideline were included. Few guidelines advise on thrombosis prophylaxis after plaster cast immobilization, (prolonged) arthroscopic surgery and isolated lower extremity trauma. Different opinions exist on the sole use of aspirin and mechanical prophylaxis and on the use of vitamin K antagonists after major hip and knee surgery.. Based on the same available literature, different guidelines recommend different thromboprophylactic regimens. Ideally, the grade of recommendation should be based on the same level of evidence world-wide. Whilst there is no agreement on the relevance of different endpoints (e.g. asymptomatic DVT), it is very difficult to reach a consensus. Thromboprophylaxis guidelines should be reviewed and updated on a regular basis, because the evidence is evolving rapidly.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Blood Loss, Surgical; Casts, Surgical; Evidence-Based Medicine; Fibrinolytic Agents; Guideline Adherence; Heparin; Hip Fractures; Humans; Knee; Lower Extremity; Orthopedic Procedures; Postoperative Hemorrhage; Practice Guidelines as Topic; Practice Patterns, Physicians'; Thrombosis; Treatment Outcome; Vitamin K

There remains uncertainty over optimal antithrombotic management strategy for patients with atrial fibrillation (AF) presenting with an acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Clinicians need to balance the risk of stroke and thromboembolism against the risk of recurrent cardiac ischaemia and/or stent thrombosis, and the risk of bleeding. This consensus document comprehensively reviews the published evidence and presents a consensus statement on a 'best practice' antithrombotic therapy guideline for the management of antithrombotic therapy in such AF patients.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Atrial Fibrillation; Benchmarking; Evidence-Based Medicine; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Patient Selection; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recurrence; Risk Assessment; Risk Factors; Stents; Stroke; Thrombosis; Treatment Outcome; Vitamin K

Antithrombotic/antiplatelet therapy after coronary stent implantation is recommended with a high level of evidence in international guidelines. However, antithrombotic/antiplatelet treatment in patients after coronary stent implantation and in addition with an indication for oral anticoagulation is still an open issue. So called "tripletherapy", the combination of oral anticoagulation with vitamin K-antagonists, clopidogrel and aspirin, is commonly used. This combination significantly increases incidence of minor and major bleedings, especially during long term use. The goal of this manuscript is to discuss the risks and potential benefit of "tripletherapy" in patients with an indication for oral anticoagulation after coronary stent implantation.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cross-Sectional Studies; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Factors; Stents; Stroke; Thrombosis; Ticlopidine; Vitamin K

Topics: Angioplasty, Balloon, Coronary; Angiotensin II Type 2 Receptor Blockers; Anticoagulants; Atrial Fibrillation; Cardiology; Coronary Disease; Drug-Eluting Stents; Heart Diseases; Humans; Morpholines; Myocardial Infarction; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Cardioembolism accounts for approximately 20% of ischaemic strokes, and is associated with high mortality and propensity to recurrences. Approximately, 30% of ischaemic strokes remain cryptogenic despite improved imaging modalities and technological improvements to identify their cause. Of the long list of various cardiac conditions associated with an increased risk of cardioembolic strokes, non-valvular atrial fibrillation is the most common cause. Unsurprisingly, the stroke risk associated with these conditions is highly variable and non-homogenous, with many risk factors additive to the overall risk profile. Treatment with vitamin K-antagonists substantially reduces the long-term complications associated with cardioembolism in some high-risk patients, for example, in atrial fibrillation. Careful selection of antithrombotic drug regime needs to be carried out in patients individually to minimise the risk of bleeding encountered with such therapy. Apart from atrial fibrillation, there is relatively limited evidence for the role of antithrombotic therapy for other cardiac conditions associated with cardioembolism and how long one should treat.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Heart Diseases; Hemorrhage; Humans; Hypertension; Ischemic Attack, Transient; Myocardial Infarction; Stroke; Thrombosis; Vitamin K

Despite limited evidence from clinical studies, anticoagulant drugs such as vitamin K antagonists (VKA) (e.g., warfarin or phenprocoumon) are widely used in the background treatment of patients with pulmonary arterial hypertension (PAH). According to current guidelines, they are generally accepted as efficacious drugs, although their efficacy is neither supported by randomised controlled trials, nor formally approved by regulatory agencies for use in the specific PAH indication. The use of these drugs is not without problems, as a paradoxical situation has to be managed in the treatment of this condition. On one hand, thrombosis is one of the key pathophysiologic features of PAH (besides vasoconstriction, proliferation and inflammation). On the other hand, the incidence of bleeding events is increased in PAH patients. This applies particularly to PAH that is related to connective tissue diseases, congenital heart disease and chronic thromboembolic pulmonary hypertension. In patients receiving VKA, caution must be observed in particular when concomitantly using prostanoids or sildenafil. Similarly, VKA doses have to be adjusted according to the labelling when using sitaxentan concomitantly. Regular International Normalized Ratio monitoring contributes to the safety of PAH patients on VKA.

Topics: Anticoagulants; Antihypertensive Agents; Endothelin Receptor Antagonists; Hemorrhage; Humans; Hypertension, Pulmonary; Thrombosis; Vitamin K

Although warfarin and other vitamin K antagonists have clearly the greatest efficacy among treatments commonly available in preventing stroke in atrial fibrillation, their use is associated with a substantial risk of major bleedings and are unpractical and difficult to use because of their narrow therapeutic window, their interaction with drugs and foods, and the need of frequent coagulation monitoring. Several new anticoagulants are now undergoing phase III clinical trials in atrial fibrillation with the aim of demonstrating noninferiority compared with vitamin K antagonists or superiority compared with aspirin in patients in whom vitamin K antagonists are contraindicated or not tolerated. These drugs fall in different pharmacological categories of oral direct thrombin inhibitors, parenteral long-lived indirect factor Xa inhibitors, and oral direct factor Xa inhibitors. Cardiologists need to be aware of the explosive pharmacological literature being accrued with these new drugs, as most of these will likely enter the clinical arena in the near future.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coumarins; Drugs, Investigational; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Injections; Platelet Aggregation Inhibitors; Risk Assessment; Stroke; Thrombin; Thrombosis; Treatment Outcome; Vitamin K

Current anticoagulant provision is dominated by parenteral low-molecular-weight heparin and oral vitamin K antagonists (VKAs), which indirectly inhibit several steps of the coagulation pathway. Two unmet needs for anticoagulation are safety and ease of use. Safety relates primarily to the incidence of major bleeding, which remains the key concern of orthopaedic surgeons and anaesthetists, over and above any efficacy advantage, and convenience of use, which centres on oral administration replacing the need for injections or monitoring platelets or coagulation with VKA. Recent research efforts towards identifying small-molecule inhibitors of coagulation enzymes as novel therapies for thrombotic disorders have been particularly successful in developing orally available molecules to directly inhibit the key proteases, factors IIa and Xa. Of the new oral anticoagulants in development, dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59-7939), which inhibit factors IIa and Xa, respectively, are the most advanced and were approved in Europe in 2008. Based on the available data, we can conclude that dabigatran etexilate is non-inferior to enoxaparin in terms of efficacy and safety, and two different doses (220 and 150 mg/day) have now been approved. The 150 mg/day dose is intended for elderly patients and those with moderate renal impairment, which allows clinicians to decrease the risk of bleeding in the increasing number of fragile patients undergoing major orthopaedic surgery. In conclusion, rivaroxaban is superior in efficacy to enoxaparin, even with the US enoxaparin dosing regimen (30 mg b.i.d.), without significant differences in safety.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Orthopedic Procedures; Prothrombin; Pyridines; Risk Assessment; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

Topics: Anticoagulants; Hemorrhage; Humans; Practice Guidelines as Topic; Thrombosis; Vitamin K

Topics: Anticoagulants; Disease Management; Hemorrhage; Humans; International Normalized Ratio; Pharmacogenetics; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Thrombosis; Vitamin K

If patients being treated with anticoagulants need to undergo an operation then physicians need to consider whether to suspend the use of this medication or to allow its use to be continued. Suspending the use of anticoagulants increases the risk of thrombosis, whereas continued use may cause bleeding complications. No evidence-based scientific research has been carried out regarding best practice for the perioperative use of anticoagulants.Antithrombotic drugs are vitamin K antagonists and platelet aggregation inhibitors. For daily practice, appropriate bridging strategies can be used for perioperative anticoagulant policy for various risk groups, such as patients with venous thromboembolism, atrial fibrillations, mechanical heart valves and coronary heart diseases (including coronary stents) and patients who have experienced a cerebrovascular accident. In the vast majority of cases the treating physician must carefully consider each individual case in order to realise the best policy.

Topics: Anticoagulants; Humans; Intraoperative Complications; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Thrombolytic Therapy; Thrombosis; Vitamin K

Cancer is linked with hypercoagulability and risk of thrombosis and this close association was recognized by Armand Trousseau in 1865. The relation between cancer and blood coagulation is reciprocal: cancer induces a hypercoagulable state and predisposes to thrombosis and activation of platelets, blood coagulation and fibrinolysis interfere with tumor cell biology, tumor growth, angiogenesis and metastatic process. In the present article, we analyze the clinical trials which assessed the influence of anticoagulant treatment on the survival of patients with cancer. The available data show that low-molecular-weight heparins (LMWHs) tend to be more effective and safer than vitamin K antagonists (VKA) in improving survival in patients with cancer. The beneficial effect of anticoagulation with either LMWHs or VKA is not universal for all patients with cancer. There are some histological types of cancers which, at early stages, appear to be more sensitive than others to the effect of anticoagulant treatment. The available clinical trials, although limited, are encouraging for the beneficial effect of anticoagulant treatment on the survival of cancer patients. More clinical trials are needed, targeting groups of patients homogenous regarding the type of cancer, the stage of the disease and life expectancy. The forthcoming clinical trials have to address some issues regarding the optimal dose, the timing and the duration of treatment with LMWH in relation to chemotherapy or other anticancer therapies.

Topics: Animals; Anticoagulants; Clinical Trials as Topic; Double-Blind Method; Drug Screening Assays, Antitumor; Fibrinolytic Agents; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Meta-Analysis as Topic; Mice; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Randomized Controlled Trials as Topic; Research Design; Survival Analysis; Thrombophilia; Thrombosis; Vitamin K; Warfarin

Vitamin K was discovered in the 1930s during cholesterol metabolism experiments in chickens. It is a fat-soluble vitamin which occurs naturally in plants as phylloquinone (vitamin K1) and is produced by gram-negative bacteria in the human gastrointestinal tract as menaquinone (vitamin K2). This vitamin was found to be essential for normal functioning of hemostasis. In addition, a number of clinical conditions in which vitamin K deficiency was found to be the underlying pathophysiologic problem were discovered. These conditions include hemorrhagic disease of the newborn, obstructive jaundice, and malabsorption syndromes. The importance of this vitamin has become more apparent with the discovery of the anticoagulant warfarin which is a vitamin K antagonist. There are millions of patients on this therapy for a variety of thrombogenic conditions such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and prosthetic cardiac valves. The wide use of this narrow therapeutic index drug has resulted in significant risk for major bleeding. Vitamin K serves as one of the major reversing agent for patients over-anticoagulated with warfarin. In the past few years, research has focused on new areas of vitamin K metabolism, which include bone and endovascular metabolism; cell growth, regulation, migration, and proliferation; cell survival, apoptosis, phagocytosis, and adhesion. These new areas of research highlight the significance of vitamin K but raise new clinical questions for patients who must be maintained on long-term warfarin therapy.

Topics: Anticoagulants; Blood Coagulation Factors; Glutamic Acid; Hemorrhage; Humans; Thrombosis; Vitamin K; Warfarin

Because 1.1 million myocardial infarctions occur in the United States alone each year, and 450,000 of them are recurrent infarctions, which carry an inherently greater risk of death and disability than first events, the importance of secondary prevention strategies that can be implemented widely is unparalleled in health care. Antithrombotic therapies, both antiplatelet and anticoagulant, have become the mainstays of these strategies. This article covers the use of chronic antiplatelet and anticoagulation agents after myocardial infarction. It does not include the management of these patients in the acute phase.

Topics: Anticoagulants; Aspirin; Azetidines; Benzylamines; Clopidogrel; Humans; Myocardial Infarction; Peripheral Vascular Diseases; Platelet Activation; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Thrombolytic Therapy; Thrombosis; Ticlopidine; Vitamin K; Warfarin

Vitamin K is an essential co-factor for the synthesis of several coagulation factors. Oral anticoagulants competitively inhibit enzymes that participate in vitamin K metabolism. The purpose of this review is to evaluate the potential interaction of dietary vitamin K and coagulation stability, particularly in the elderly patient.. Recent prospective evidences suggest that dietary vitamin K plays an essential role in anticoagulation stability. Vitamin K intake of more than 250 microg/day was shown to decrease warfarin sensitivity in anticoagulated patients consuming regular diets. In a randomized crossover study, brief periods of changes on vitamin K intake also had significant effects on coagulation parameters. Patients that were allocated to an 80% decrease of intake increased International Normalized Ratio (INR) by almost 30% 7 days after the intervention. Similarly, it was estimated by dietary records that for each increase in 100 microg of vitamin K intake, the INR would be reduced by 0.2. A recent study also demonstrated that over-the-counter multivitamin supplements contain enough vitamin K1 to significantly alter coagulation parameters.. Contemporary data strengthen the concept that the interaction between dietary vitamin K and coumarin derivatives is clinically relevant and plays a major role in INR fluctuations in chronic anticoagulated patients.

Topics: Aged; Aging; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Diet; Food-Drug Interactions; Humans; Phenprocoumon; Thrombosis; Vitamin K; Warfarin

The expanding demand for long-term antithrombotic therapy and the major limitations of the vitamin-K antagonists, namely their narrow therapeutic range, numerous drug interactions and need for laboratory monitoring, have stimulated the development of new antithrombotic agents. Direct thrombin inhibitors and factor Xa inhibitors are the new classes of orally available anticoagulants that are most advanced in development. Large clinical trials evaluate several compounds both in the primary and secondary prevention of venous thromboembolism and in the prevention of cardioembolism in patients with atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation Factors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Thrombosis; Vitamin K

The hemostatic system in its multiple components displays an intricate organization in time which is characterized by circadian (approximately 24-hour), circaseptan (approximately 7-day), menstrual (approximately monthly), and circannual (approximately yearly) bioperiodicities. The interaction of the rhythms of the variables participating in hemostasis determine transient risk states of thromboembolic events, including myocardial infarction and stroke, and of hemorrhage and hemorrhagic events, each with a unique timing. The circadian staging of the rhythms in vascular, cellular, and coagulation factors that favors blood coagulation and thrombosis coincides with the daily minimum in fibrinolytic activity; as a result there is elevated risk in the morning of acute myocardial infarction and stroke. Similar hemostatic rhythms may determine the epidemiology of thromboembolic and hemorrhagic events during the week, month and year. This article focuses on the large-amplitude circadian rhythms operative in the hemostatic system. Their implication for preventive and curative pharmacotherapy of hemostatic disorders is presented, with discussion of related problems.

Topics: Autonomic Nervous System; Blood Coagulation; Blood Coagulation Disorders; Chronobiology Phenomena; Circadian Rhythm; Female; Fibrinolysis; Hemostasis; Heparin; Humans; Menstrual Cycle; Platelet Aggregation Inhibitors; Platelet Count; Thrombolytic Therapy; Thrombosis; Vitamin K

Life-threatening intracranial hemorrhage, predominantly intracerebral hemorrhage (ICH), is the most serious complication of oral anticoagulant therapy (OAT), with mortality in excess of 50%. Early intervention focuses on rapid correction of coagulopathy in order to prevent continued bleeding.. This article reviews the epidemiology of OAT-associated ICH (OAT-ICH), and current treatment options, with the aim of providing a framework for future studies of unresolved questions. A number of acute treatments are available, but all have a significant risk of inducing thrombosis and other side effects, and vary in their rapidity of effect: vitamin K (very slow response time), fresh frozen plasma (slow response time, large volume of fluid required, transfusion-related acute lung injury), prothrombin complex concentrates, and recombinant activated factor VII. Current practice is to administer a combination of vitamin K and either fresh frozen plasma or prothrombin complex concentrates; the occasional use of recombinant activated factor VII has been reported. No prospective study has addressed the efficacy of, or outcomes from, the use of these practices.. Current management of OAT-ICH is varied and not based on evidence from randomized controlled trials. Well-designed clinical trials are essential if we are to identify the effective acute treatments for OAT-ICH that are urgently needed.

Topics: Administration, Oral; Anticoagulants; Cerebral Hemorrhage; Clinical Trials as Topic; Factor VIIa; Hemorrhage; Humans; Recombinant Proteins; Risk; Thrombosis; Vitamin K

Provided that account is taken of the criteria discussed in the present article, there is no doubt about the therapeutic benefits of effective anticoagulation in patients with chronic atrial fibrillation. Indeed, it is to be expected that the previously valid therapeutic guidelines are more likely to be expanded to reduce feared thromboembolic complications to a minimum, as is exemplified by the recommendation that the application of anticoagulation treatment with vitamin K antagonists should be continued over the longer term, that is, after the restoration of sinus rhythm. Furthermore, there is hope that effective drugs with a calculable (level of) safety and simplicity of administration may soon become available.

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Echocardiography; Electric Countershock; Fibrinolytic Agents; Heart Diseases; Humans; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Factors; Stroke; Thromboembolism; Thrombosis; Time Factors; Vitamin K

Vitamin K, heparin and their antagonists remain the basis of coagulation therapies today, more than half a century after their discovery. Failure of blood clotting in chicks that were fed a fat-depleted diet was observed by William McFarlane, William Graham Jr. and Frederick Richardson of the Ontario Agricultural College; it led to the search that yielded vitamin K. Investigation of hemorrhagic disease in cattle by Francis Schofield of the Ontario Veterinary College found an anti-thrombin substance in spoiled clover which was later characterized as dicoumarol, a vitamin K antagonist, and led to the development of warfarin. In Toronto, a systematic approach lead by Charles Best resulted in the world's first plentiful supply of purified heparin. Clinical usefulness of heparin in thrombosis, embolism, cardiovascular surgery, dialysis and transplantation was demonstrated first by Gordon Murray and Louis Jaques. The roles and the careers of Canadian coagulation research pioneers are briefly presented in this review, which shows how clinical medicine benefited by the systematic development of agricultural science in Guelph, Ontario.

Topics: Agriculture; Animals; Anticoagulants; Canada; Coagulants; Heparin; History, 20th Century; Humans; Thrombosis; Vitamin K; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Belgium; Factor X; Fibrinolytic Agents; Hematoma; Heparin, Low-Molecular-Weight; Humans; Nerve Block; Platelet Aggregation Inhibitors; Thrombin; Thrombosis; Vitamin K

Asymptomatic elevation of the international normalized ratio (INR) is a common problem associated with hemorrhage. Evidence from randomized controlled trials supports the use of low-dose oral vitamin K therapy as a treatment that promptly reduces the INR. Vitamin K given orally is more effective than subcutaneous vitamin K injection, and as effective as intravenous administration when INR values are compared 24 hours after administration. A 1.0-mg vitamin K dose is likely most appropriate for patients with INR values between 4.5 and 10. The fear of over-correction of the INR has limited the widespread use of vitamin K; however, our review suggests that this occurs infrequently when small doses are administered orally.

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Hemorrhage; Humans; International Normalized Ratio; Thrombosis; Vitamin K; Warfarin

The news concerning anticoagulant therapy is very rich. It was also keenly awaited in view of the real imperfection of antivitamin K drugs on which the present strategy of prevention of thromboembolic risk related to atrial fibrillation is based. The new anticoagulants have differing targets identified from the physiological mechanism of coagulation and the physiopathology of thrombosis.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Thrombosis; Vitamin K

There has been an explosion of new anticoagulants in recent years. new parenteral anticoagulants have been developed to overcome the limitations of heparin and low molecular weight heparin , whereas novel orally active anticoagulants have been designed to provide more streamlined therapy than vitamin K antagonists. Focusing on drugs in more advanced stages of clinical testing, this review identifies the molecular targets of new anticoagulants, describes the results of clinical trials, and provides perspective on the opportunities for new anticoagulants.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Humans; Thrombosis; Vitamin K

Anti-thrombin, anti-platelet and anti-vitamin K agents are common treatments given for the prevention of thrombotic or embolic events. In oral or maxillofacial surgery, the question is whether oral anticoagulants or anti-platelets should be discontinued or not: temporary interruption could limit the risk of bleeding, but would increase the risk of thrombosis, and inversely. The best risk/benefit ratio must be achieved, but in many cases anti-platelet agents or even anti-vitamin K agents can be continued. In case of "potentially hemorrhagic" oral surgery, anti-platelet agents should be interrupted about ten days before the intervention. Anti-vitamin K agents should be interrupted four days before surgery and if required, replaced by low-molecular weight heparin at preventive or curative doses. In the very large majority of patients however, surgery (avulsion for example) can be performed without interrupting anticoagulation. Data in the literature have demonstrated that despite the theoretical risk of hemorrhage, bleeding is minimal and can be easily controlled by local treatments; the risk of thrombotic or thromboembolic events after discontinuing anticoagulation is much greater. A close collaboration between the dentist, the stomatologist, and the clinician is required to determine whether anti-thrombosis prevention should be continued and whether the anticoagulation level is adapted to the thrombotic risk. Good surgical technique and local anti-hemorrhagic treatment are essential in oral surgery, particularly in patients taking anti-platelets or oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Dental Care for Chronically Ill; Humans; Interprofessional Relations; Oral Hemorrhage; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Thrombosis; Tooth Extraction; Vitamin K

Thrombin has long been a target for development of oral anticoagulants but it has been difficult to find synthetic inhibitors with a desirable combination of pharmacodynamic and pharmacokinetic properties. However, there are now two oral direct thrombin inhibitors (DTIs) in clinical development, ximelagatran (ExantaTM) and BIBR 1048. Both are prodrugs with two protecting groups that are eliminated after absorption from the gastrointestinal tract. Their main active substances, melagatran and BIBR 953, are both potent and selective DTIs. In experimental models of thrombosis, melagatran has been shown to have a shallower dose-response curve than warfarin and, therefore, a better separation between efficacy and bleeding. Oral bioavailability, measured as the plasma concentration of the active metabolite, seems to be higher for ximelagatran (20%) than for BIBR 1048 (estimated to 5%). BIBR 953 has a longer half-life (about 12 h) than does melagatran (3-5 h) after oral administration of BIBR 1048 and ximelagatran, respectively. Both melagatran and BIBR 953 are mainly eliminated via the renal route. The variability of the plasma concentration of melagatran after oral administration of ximelagatran is low. There are no clinically relevant interactions with food or cytochrome P450 metabolized drugs and ximelagatran. In clinical studies, ximelagatran has been administered in a twice-daily fixed-dose regimen without coagulation monitoring. Results of published clinical studies are encouraging, both with regard to efficacy and bleeding. Major indications in Phase III studies with ximelagatran are the prevention of venous thromboembolism (VTE) in hip and knee replacement surgery, treatment and long-term secondary prevention of VTE and prevention of stroke in patients with nonvalvular atrial fibrillation. It is anticipated that with a favourable outcome of the Phase III clinical studies new oral DTIs, with the oral fixed-dose regimen without routine coagulation monitoring, will ease the use of today's anticoagulant therapy.

Topics: Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Glycine; Hemostasis; Humans; Prodrugs; Pyridines; Stroke; Thrombin; Thrombosis; Venous Thrombosis; Vitamin K

Chronic peripheral arterial disease (PAD) is frequently treated by implantation of either an infrainguinal autologous venous or artificial graft. One-year occlusion rates for infrainguinal bypasses vary between 15 and 75%, depending on the site of distal anastomosis, length, quality, and material of the graft, but also on other factors such as proximal inflow and distal outflow conditions. To prevent graft occlusion, patients are usually treated with either an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion.. To evaluate whether antithrombotic treatment in patients with chronic PAD undergoing infrainguinal bypass surgery improves graft patency, limb salvage and survival by performing a meta-analysis of performed RCTs.. The search strategy was that adopted by the Cochrane Review Group on Peripheral Vascular Diseases. Additional data bases were reviewed (Reference lists of papers resulting from this search, MEDLINE from 1966-onwards and EMBASE from 1980-onwards using the terms 'anticoagulant' and 'arterial surgery'.. The methodological quality of each trial was assessed independently by at least two reviewers using the checklist provided by the Peripheral Vascular Diseases Collaborative Review Group, with emphasis on concealment of randomisation. Each trial was given an allocation score of A (clearly concealed), B (unclear if concealed), or C (clearly not concealed) and a summary score of A (low risk of bias), B (moderate risk), or C (high risk). Trials scoring A were included and those scoring C were excluded. For a trial scoring B, an attempt was made to obtain more information by contacting the author.. For each trial, the number of patients originally allocated to each treatment group was extracted from the data and an 'intention to treat' analysis performed. Data collection on each trial included inclusion and exclusion criteria, patient details, type of graft, type and dose of antithrombotic therapy used, outcome, and side effects. The treatment and control groups were compared for important prognostic factors and differences described. If any of the above data was not available, further information was sought from the author. However, the heterogeneity between trials could not be tested due to inaccessible data. Data were synthesized by comparing group results.. The analysis including four trials which evaluated vitamin K antagonists (VKA) versus no VKA indicate, that oral anticoagulation tendentially favours venous but not artificial graft patency as well as limb salvage and survival. Two other studies comparing VKA with aspirin or aspirin/dipyridamole supported evidence for a positive effect of VKA on the patency of venous but not artificial grafts. Subgroup analysis for artificial grafts as performed in one trial showed a favourable effect of antiplatelet agents on synthetic bypasses. In two trials with a relatively small number of patients low molecular weight heparin treatment was associated with a lower incidence of early postoperative graft thrombosis compared to treatment with unfractionated heparin. In one trial infusion of antithrombin concentrate was reported to have a negative effect on intraoperative graft thrombosis necessitating the study to be stopped before termination. Perioperative administration of ancrod was compared to unfractionated heparin showing no benefit of one drug compared to the other.. Patients operated for an infrainguinal venous graft might benefit from treatment with VKA, whereas patients receiving an artificial graft might profit more from platelet inhibitors (aspirin). However, the evidence is not conclusive. Randomised controlled trials with larger patient numbers comparing antithrombotic therapies with either placebo or antiplatelet therapies are called for in the future.

Topics: Arteriosclerosis; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Intermittent Claudication; Ischemia; Leg; Peripheral Vascular Diseases; Postoperative Complications; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

Anticoagulants are widely used for the prevention and treatment of venous and arterial thrombosis. Current treatment strategies often employ a combination of parenteral and oral agents because the only available orally active anticoagulants, vitamin K antagonists, have a delayed onset of action. Furthermore, vitamin K antagonists have a narrow therapeutic window that necessitates careful anticoagulation monitoring, and dosing is problematic because of multiple food and drug interactions. These limitations highlight the need for oral anticoagulants that produce a more predictable anticoagulant response than vitamin K antagonists, thereby obviating the need for laboratory monitoring. Ximelagatran has the potential to meet this need. A prodrug of melagatran, an agent that targets thrombin, ximelagatran exhibits many of the characteristics of an ideal anticoagulant. This article (1). reviews the limitations of vitamin K antagonists, (2). lists the characteristics of an ideal anticoagulant, (3). rationalizes thrombin as a target for new anticoagulants, (4). reviews the preclinical and clinical data with ximelagatran, and (5). provides clinical perspective as to the future of ximelagatran and other orally active anticoagulants currently under development.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Blood Coagulation; Drug Monitoring; Glycine; Humans; International Normalized Ratio; Postoperative Complications; Prodrugs; Stroke; Thrombin; Thrombosis; Venous Thrombosis; Vitamin K

Vitamin K antagonists (VKA) decrease the synthesis of the active forms of four coagulation factors (factors II, VII, IX, X) and three inhibitors (proteins C, S, Z). There are VKA having a short half life (Sintrom, Pindione) and VKA having a long half life (Apegmone, Previscan, Coumadine). The treatment is monitored by the INR which in the majority of the indications must range between two and three. The first INR is usually performed 36 to 72 h after starting the treatment. There are a number of drug interactions. The rate of major bleedings range from 1.1 to 4.9 for 100 patient-year according to the published studies. Since around 600,000 patients are treated by VKA in our country, the absolute number of serious bleeding is high (> or = 17,000 per year). Anticoagulant clinics are structures aimed to instruct the patient and to advise the general practitioner to monitor the treatment, using computer assisted methods. It has been reported that these structures reduce the incidence of bleeding and of thrombotic events by 3 to 4 times.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Drug Interactions; Family Practice; Food; Hemorrhage; Humans; Patient Education as Topic; Phenindione; Thrombosis; Time Factors; Vitamin K; Warfarin

Topics: Aged; Aspirin; Atrial Appendage; Atrial Fibrillation; Humans; Intracranial Embolism; Prevalence; Randomized Controlled Trials as Topic; Risk Assessment; Stroke; Thrombosis; Vitamin K; Warfarin

In the cardiac patient, there are clinical situations where antivitamin K is indicated more by the co-existing pathological associations or by a particular thrombogenic situation than by the cardiac disease itself. The presence of an embologenic abnormal rhythm, an apical thrombus or a large anterior akinesis are recognised as situations where antivitamin K must be discussed and, except for absolute contraindication, initiated. The studies undertaken for several decades are highly instructive and their contributions are considerable in the different questions which could be asked regarding the efficacy of antivitamin K. In particular they have the merit of signalling the correct directions to take and the errors to avoid. Concerning the evolution of cardiac disease, it must be admitted that the very good results of antivitamin K treatment alone at high dose are to be balanced against their haemorrhagic risk. The studies testing the association of low-dose aspirin with moderate-dose antivitamin K (INR 2 to 2.5) are to date very promising. The evaluation of the understanding of the treatment by patient education remains a major stage when initiating antivitamin K treatment in the cardiac patient.

Topics: 4-Hydroxycoumarins; Anticoagulants; Cardiovascular Diseases; Hemorrhage; Humans; Indenes; Risk Factors; Thrombosis; Vitamin K

Thrombotic occlusion after vascular reconstructive surgery is a frequent complication, specially when low-flow arteries and arterial prostheses are involved. Heparin therapy is usually administered in acute arterial insufficiency, and also during the perioperative period, in order to limit thrombus formation or propagation at the surgical or the cross-clamp application sites. The overall benefit of antiplatelet agents, specially aspirin, during the pre, peri and postoperative periods has been clearly demonstrated for arterial prostheses, and is probably useful in venous bypasses. Aspirin therapy also prevents thrombotic complication in other vascular beds, and reduces long-term cardiovascular morbidity and mortality. Oral anticoagulation by vitamin K antagonists, alone or combined with aspirin is perhaps an appropriate choice in selected patients with high risk of graft thrombosis, but cannot be recommended for routine treatments because of an increased risk of hemorrhage.

Topics: 4-Hydroxycoumarins; Anticoagulants; Arteries; Aspirin; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Indenes; Platelet Aggregation Inhibitors; Postoperative Complications; Thrombosis; Vascular Surgical Procedures; Vitamin K

Topics: Anticoagulants; Catheters, Indwelling; Fibrin; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Topics: Animals; Fibrinolytic Agents; Hemostasis; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Receptors, Purinergic P2; Recombinant Proteins; Thrombosis; Vitamin K

Topics: Blood Coagulation; Hemophilia A; Humans; Protein C; Thrombosis; Vitamin K

The antiphospholipid syndrome was individualized 12 years ago. Treatment was initially based on steroids, immunosuppressive drugs and intravenous immunoglobulin therapy. More recently, several retrospective studies have established that in most clinical conditions therapeutic doses of oral vitamin K antagonists (INR > or = 3) are sufficient to control the disease.. However, high dose immunoglobulin therapy is still indicated in a few cases, especially in life-threatening immune peripheral thrombocytopenia, and in recurrent foetal loss: in the latter indication, immunoglobulin therapy alone is efficient in 80% of cases.. Prospective studies are needed to assess the efficacy of intravenous immunoglobulin therapy in neurological complications occurring in spite of anticoagulant therapy, and in the context of repeated foetal losses when antithrombotic therapy with aspirin and subcutaneous heparin has failed.

Topics: Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Humans; Immunoglobulins, Intravenous; Patient Selection; Prospective Studies; Retrospective Studies; Thrombocytopenia; Thrombosis; Treatment Outcome; Vitamin K

Continuous or intermittent use of unfractioned heparin is the anticoagulant of choice to prevent the extracorporeal circulation clotting during the hemodialysis session. However, low molecular weight heparin (LMVH) could be an alternative treatment especially in case of high risk bleeding or during some clinical conditions such as diabetes mellitus, cerebrovascular bleeding, malignant hypertension. LMVH may be given as a single initial bolus injection generally adequate. Heparinization must be lowered or stopped when an effective anticoagulation is previously used.

Topics: Anticoagulants; Contraindications; Extracorporeal Circulation; Hemorrhage; Heparin; Heparin Antagonists; Heparin, Low-Molecular-Weight; Humans; Kidney Failure, Chronic; Protamines; Renal Dialysis; Risk Factors; Thrombosis; Vitamin K

Topics: Drug Hypersensitivity; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Thrombocytopenia; Thrombosis; Vitamin K

Numerous clinical trials have been performed to identify the optimal therapeutic range for various indications in patients receiving warfarin. Other studies have identified risk factors for hemorrhage and thromboembolism to decrease the risk of these complications. A more consistent approach, using guidelines presented in this article, toward initiation, monitoring, and reversal of anticoagulation should further decrease the incidence of complications.

Topics: Anticoagulants; Drug Interactions; Heart Valve Prosthesis; Heparin; Humans; Thrombosis; Vitamin K; Warfarin

Topics: Administration, Oral; Animals; Anticoagulants; Drug Interactions; Humans; Prothrombin Time; Thrombosis; Vitamin K; Warfarin

Coumarin derivatives and anticonvulsants administered during pregnancy enter the fetal circulation, interfering with the action of vitamin K. Vitamin K plays a crucial part in the gamma-carboxylation of glutamic acid residues of the vitamin K-dependent coagulation factors prothrombin, FVII, FIX, and FX. Other vitamin K-dependent proteins in the coagulation cascade are protein C and protein S. Vitamin K-dependent bone proteins are osteocalcin and gamma-carboxyglutamate matrix protein. Administration of coumarol derivatives results in under carboxylation of the vitamin K-dependent proteins. Anticoagulation therapy with warfarin is followed by an increased risk of embryopathy, which has been shown to be greatest between gestational weeks 6 and 12. Administration of warfarin is also followed by an increased risk both of fetal intraventricular hemorrhage, and of cerebral microbleedings, which may result in microencephaly and mental retardation. Treatment with coumarol derivatives should therefore be avoided during pregnancy, even in pregnant women with artificial heart valves, and replaced by heparin. Hemorrhage in the newborn related to the use of anticonvulsant drugs during pregnancy occurs very early within the first 24 hours, probably due to increased degradation of vitamin K. Transplacental administration of vitamin K has been shown to prevent neonatal hemorrhage induced by maternal anticonvulsant therapy. Prophylactic administration of vitamin K, especially by intramuscular injection, has been reported to be associated with an increased risk of childhood cancer. However, subsequent extensive studies have yielded no evidence of any relationship between prophylactic vitamin K administration and the occurrence of childhood cancer.

Topics: Abnormalities, Drug-Induced; Anticoagulants; Anticonvulsants; Blood Coagulation Factors; Child; Cohort Studies; Coumarins; Epilepsy; Female; Fetal Diseases; Hemorrhage; Humans; Infant, Newborn; Maternal-Fetal Exchange; Neoplasms; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Protein Processing, Post-Translational; Sweden; Thrombosis; United Kingdom; Vitamin K; Vitamin K Deficiency

Eighteen patients with an acute thrombosis of the splanchnic veins were reviewed. Most of apparently idiopathic cases of splanchnic vein thrombosis are related to an increased coagulation related to a congenital or acquired defect of haemostasis. The aim of this study was to assess the effects of a new and effective treatment. Nine male and 9 female patients (range of age: 19 to 81 years) experienced a mesenteric venous thrombosis. There were 14 mesenteric vein thromboses with infarction, two transient mesenteric venous ischaemias without bowel infarction and two acute thromboses of the splanchnic veins without bowel ischaemia. A coagulopathy was detected in seven patients: oral contraception, protein C (PC) or antithrombin III (AT III) congenital deficiencies, acquired deficiency of AT III, PC and protein S (PS), polycythaemia in the post-partum period and primary myeloproliferative disorder. No coagulopathy was associated with thrombosis in eight cases: mesenteric haematoma, splenomegaly, cirrhosis, appendicectomy, cholescytectomy, chronic heart failure, treatment with beta-adrenergic receptor antagonist and digitalis, stenosis of the portal anastomosis after liver transplantation. Twelve patients required surgery: eight intestinal bowel resections with immediate anastomosis, four resections without immediate anastomosis. Only one patient underwent a second look for a repeat bowel resection. No death occurred in the early postoperative period and 17 out of 18 patients were alive after 12 years. An oral anticoagulant therapy was undertaken from two months to seven years. However, three patients suffered a recurrent thrombosis. Two of them required a long-term anticoagulation. Six patients experienced a portal hypertension and oral anticoagulants were discontinued in three of them because of bleeding oesophageal varices. Six patients were treated only by unfractionated heparin (UFH) or low molecular weight heparin (LMWH) followed by oral anticoagulants. After laparotomy, two were only treated with UFH without any bowel resection, as mesenteric venous ischaemia was too extensive. These observations suggest that the choice between an appropriate medical or surgical treatment is important and must be discussed. Since 1989, the therapeutic choice has been modified by ultrasonography and contrast enhanced computed tomographic scan which confirms diagnosis, allows to follow up and check the effects of anticoagulation and to choose the time for surgery. When the

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Blood Coagulation Disorders; Female; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Protein C Deficiency; Protein S Deficiency; Risk Factors; Thrombosis; Vitamin K

Topics: Anesthesia; Aspirin; Bandages; Dextrans; Female; France; Heparin, Low-Molecular-Weight; Humans; Male; Postoperative Complications; Pulmonary Embolism; Thrombosis; Vitamin K

Clinical indications of vena cava interruption are reviewed. During the last few years pulmonary embolism frequency remained high and many new percutaneous vena caval filters became available. These facts probably explain the increasing use of these filters reaching about 10,000 filters each year in France. Existing data show that: embolic risk with antithrombotic agents is less than 5%, probably not far greater than embolic risk with cava filters (about 2%); complications encountered with the filters are caval thrombosis in 8%, and more or less than 4% other major complications; there is no controlled study comparing antithrombotic treatment associated with caval filters to antithrombotic treatment alone; there is no controlled study comparing new cava filters among them or to the Greenfield filter; economical implications of caval filters are mostly unknown. The only admitted indications of vena cava interruption, in case of proximal venous thrombosis, are contraindications to anticoagulation. In other situations no data allow to recommend a cava filter; indication will be discussed on a case by case basis. Prospective controlled studies are greatly encouraged.

Topics: Heparin; Humans; Ligation; Pulmonary Embolism; Recurrence; Thrombosis; Vena Cava Filters; Vena Cava, Inferior; Vitamin K

The families of eight unrelated patients were studied with regard to a hereditary deficiency in antithrombin III (ATIII), protein C, or protein S. These deficiencies were recognized in the course of investigations for deep-vein thrombosis (DVT) in the eight patients. A group of 31 individuals (patients and family members), mostly less than 40-year-old was explored. Two cases of AT III deficiency were discovered, as well as 21 of protein C deficiency, and seven of protein S. Ten of the 30 have had recurrent venous thrombosis at the time of bedrest, trauma, surgery, pregnancy, postpartum or during oral contraceptive treatment. Spontaneous DVT occurred in three cases. Seventeen patients had remained asymptomatic till then. Such patients need antithrombotic treatment during surgery or pregnancy. Prophylactic treatment with enoxaparin in one patient (deficiency in protein C) during her second pregnancy is discussed. It seems that low molecular weight heparin may be a safe alternative to unfractionated heparin. Oral anticoagulants are efficient in preventing reoccurring venous thromboembolism in patients with AT III deficiency. The questions of whether oral anticoagulants should be continued in the long-term in patients with protein C or protein S deficiency who have had a DVT, and whether asymptomatic deficient patients should be given any antithrombotic treatment outside circumstances likely to induce a DVT, remain as yet unanswered.

Topics: Adolescent; Adult; Antithrombin III; Antithrombin III Deficiency; Blood Coagulation Disorders; Child; Female; Glycoproteins; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pedigree; Protein C; Protein C Deficiency; Thrombosis; Vitamin K

New trends in antithrombotic therapy should reside in a better adaptation, both in potency and in target to the involved thrombogenic mechanism. Thrombogenesis as hemostasis is the result of cooperation between plasma coagulation factors and platelet functions, and these two systems are themselves in equilibrated antagonism with the vessel wall, mainly endothelial cells. These triangular relations between coagulation factors, platelet functions, and endothelial cell reactivity are quantitatively regulated by flow conditions. The relative importance of each of these protagonists in the genesis of vascular thrombosis varies along the vascular tree, mainly due to changes in flow characteristics, and explain the usual separation between venous and arterial thrombosis: venous thrombosis involves mainly coagulation factors and the vascular fibrinolytic response whereas arterial thrombosis involves the thromboresistant characteristics of the endothelial cell membrane and platelet functions. The real blood flow characteristics may be altered by local disease and influences the relative involvement of coagulation and fibrinolytic factors, platelet functions, and endothelial cells. Prevention of thrombosis must take into account all these phenomena and must be targeted to the predominant factor or factors. Depending on the local conditions, the therapeutical goal can be: (1) limitation of platelet functions or coagulation factors; (2) stimulation of thromboresistant properties of the endothelium (mainly its profibrinolytic characteristics); and (3) modification of the flow conditions. Several targets can be associated: the level of inhibition or stimulation of a function depends on the dysequilibrium, and efficient prevention does not always require complete inhibition of a function. Once a thrombus has developed, antithrombotic treatment will prevent its extension, and thrombolytic therapy will try to restore vascular patency. Once patency has been restored antithrombotic therapy is still needed to prevent recurrence of the thrombus. Even if the main targeting is on platelets, the choice in the molecule to be clinically used must be defined by the function of the platelet involved: thrombogenesis or vasospasm, and even by the metabolic pathway predominantly activated. In coagulation strategy, differences must be drawn between antithrombotic therapy directed against thrombin formation, complexes of coagulation, free enzymes or activation phases. In thrombolytic the

Topics: Fibrinolytic Agents; Heparin; Humans; Platelet Aggregation Inhibitors; Thrombophlebitis; Thrombosis; Vitamin K

Oral anticoagulants are used extensively, although their risks are not always fully recognized. The prophylaxis of venous thrombosis after hip surgery, the prevention of deep venous thrombosis and pulmonary emboli after an acute episode of these, the prevention of arterial emboli from the heart in patients at risk, and the prophylaxis of thrombosis in patients with congenital deficiency of antithrombin III, protein C, or protein S are some of the indications for oral anticoagulant use. Warfarin sodium is contraindicated in pregnancy, however. The recommended prothrombin time is 1 1/2 to two times control, lower than previously. The major risk of oral anticoagulant therapy, bleeding, is treated with vitamin K or plasma, depending on its severity. Warfarin necrosis and the "purple-toe" syndrome are seen more frequently than realized.

Topics: Absorption; Administration, Oral; Biological Availability; Drug Interactions; Hemorrhage; Hip Fractures; Humans; Myocardial Infarction; Necrosis; Postoperative Complications; Protein Binding; Prothrombin Time; Pulmonary Embolism; Thrombophlebitis; Thrombosis; Vitamin K; Warfarin

A number of drugs such as unfractionated heparin, oral anticoagulants, and agents inhibiting platelet function, are being used in the prevention of arterial thrombosis; novel antithrombotic substances are in the making. Among the latter are low-mol-wt heparin and semisynthetic heparin analogs, unfractionated and low-mol-wt heparin covalently complexed or not with anti-thrombin III, pyridoxal phosphate, scavengers of free radicals, synthetic inhibitors of serine proteases, and stimulators of endogenous fibrinolysis.

Topics: Anticoagulants; Blood Coagulation Factors; Blood Proteins; Fibrinolysis; Free Radicals; Heparin; Humans; Lipid Peroxides; Platelet Adhesiveness; Platelet Aggregation; Platelet-Derived Growth Factor; Protease Inhibitors; Prothrombin Time; Pyridoxal Phosphate; Serine Endopeptidases; Thrombosis; Vitamin E; Vitamin K

Topics: Adenosine Diphosphate; Animals; Anticoagulants; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Clinical Trials as Topic; Cyclic AMP; Epinephrine; Fibrinolytic Agents; Heparin; Humans; Thrombin; Thrombosis; Vitamin K

Topics: Aged; Animals; Arteriosclerosis; Ascorbic Acid; Avitaminosis; Calcium; Humans; Lipid Metabolism; Thrombosis; Vitamin A; Vitamin B Complex; Vitamin E; Vitamin K; Vitamins

Topics: Animals; Blood Coagulation Factors; Chemical Fractionation; Chromatography, DEAE-Cellulose; Dogs; Factor IX; Factor IXa; Factor VII; Factor VIII; Factor X; Hemophilia B; Hepatitis B; Hepatitis C; Humans; Partial Thromboplastin Time; Prothrombin; Thrombosis; Vitamin K

Topics: Antithrombin III Deficiency; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrinolysis; Hemostasis; Humans; Neoplasms; Thrombosis; Vitamin K

Medical progress owes a great deal to the fundamental medical sciences and to the application of chemistry, physics and mathematics to medical problems. However, clinical observations and investigations are still of decisive importance in any field of medicine. By a feed-back mechanism they may even stimulate and fertilize fundamental medical sciences. Thus, our knowledge of the blood coagulation mechanism has been considerably enlarged by clinical analysis of hereditary bleeding disorders. - Chemotherapy of neoplastic diseases started from clinical observations during World War I (production of leucopenia by sulfur mustard gas). - Surgical procedures and their consequences have contributed greatly to our knowledge of thyroid function, of the segmental anatomy of the lung, and of the conduction system of the heart. - Observations of side effects of drugs have often enlarged or completely changed their primary clinical indications: from antibacterial sulfonamides, anti-diabetic, antihypertensive and powerful diuretic drugs have been developed, and from histaminics the modern neuroleptics and antidepressants. - Fundamental immunology has been enormously activated by clinical transplantation of kidney and bone marrow. Selective immunological defects in men, real experiments of nature, contributed much to our knowledge of the various types of allergic response. The quality of clinical investigations, particularly of controlled clinical trials, has been considerably improved during the last two decades. Although it is an applied science the reliability of its results is to-day comparable with that of "pure" natural sciences. However, medicine is more than a natural science: examples of outstanding scientists who at the same time were great and human physicians are presented.

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Arthritis; Cardiac Catheterization; Clinical Trials as Topic; Diabetes Mellitus; Dicumarol; Electroencephalography; Heart Conduction System; Humans; Research Design; Sulfonamides; Thrombosis; Thymus Gland; Thyroid Gland; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Disseminated Intravascular Coagulation; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Liver Diseases; Thrombosis; Vitamin K

There are three categories of antithrombotic agents: drugs which prevent fibrin fromation (the anticoagulants and defibrinating enzymes), drugs which prevent platelet adhesion or aggregation (the antiplatelet drugs), and thrombolytic drugs which induce fibrin degradation. Clinical studies have now led to a better understanding of the relative value of these drugs in different thrombotic disorders. In addition, knowledge of the mechanism of action of some of these drugs has recently been much advanced. The anticoagulant drugs in clinical use are heparin and the oral anticoagulants. Heparin is a potent inhibitor of several steps on the intrinsic coagulation pathway through its effect on a plasma cofactor, antithrombin III. its action is immediate, but heparin must be given parenterally. Oral anticoagulants act more slowly, by reducing the hepatic synthesis of biologically active factors II, VII, IX and X, but can be given by mouth. Heparin is therefore most suitable for starting anticoagulant treatment, while oral anticoagulants are generally used for prolonged therapy. The value of the anticoagulants as antithrombotic agents has been best assessed by studying their effectiveness in preventing and treating venous thromboembolic disease. Oral anticoagulants have been repeatedly shown to prevent venous thrombosis and pulmonary embolism in patients at high risk of developing these complications. However, the increased risk of postoperative bleeding has prevented their widespread use for this purpose in surgical patients. Recently, the use of low doses of heparin, given subcutaneously before and after surgery, has been shown to markedly reduce the incidence of venous thrombosis and pulmonary embolism (including fatal pulmonary embolism) after major elective abdominal surgery, and to produce only a slight increase of postoperative bleeding. This represents a major advance in anticoagulant prophylaxis of venous thromboembolism insurgical patients. However, low dose heparin prophylasix is relatively ineffective in patients having hip surgery, and has not been evaluated in patients having other types of orthopaidic surgery. There is direct evidence that antocoagulant therapy prevents death and recurrent embolism in patients who have developed pulmonary embolism, and considerable indirect evidence that it prevents pulmonary embolism, and considerable indirect evidence that it prevents pulmonary embolism (and death from pulmonary embolism) in patients who have venous

Topics: Anticoagulants; Antidotes; Drug Interactions; Fibrinolytic Agents; Hemostasis; Heparin; Humans; Thromboembolism; Thrombophlebitis; Thrombosis; Vitamin K

Topics: Barbiturates; Biotransformation; Depression, Chemical; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance; Embolism; Enzyme Induction; Hemorrhage; Humans; Liver; Male; Middle Aged; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation Tests; Choroid; Fibrinolytic Agents; Heparin; Humans; Hyperbaric Oxygenation; Parasympatholytics; Platelet Adhesiveness; Retinal Hemorrhage; Retinal Vein; Retinal Vessels; Streptokinase; Thrombophlebitis; Thrombosis; Vasodilator Agents; Visual Fields; Vitamin K

Topics: Binding Sites; Blood Coagulation; Drug Antagonism; Drug Synergism; Hemorrhage; Humans; Prothrombin Time; Thrombosis; Vitamin K; Warfarin

Topics: Administration, Oral; Adrenal Cortex Hormones; Animals; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Clofibrate; Coumarins; Diuresis; Dogs; Heparin; Humans; Hypnotics and Sedatives; Liver Diseases; Metabolic Diseases; Phenylbutazone; Rats; Salicylates; Sulfonamides; Thrombosis; Uremia; Vitamin K

Subclinical obstructive valve thrombosis after transcatheter aortic valve replacement (TAVR) is of uncertain frequency and clinical impact.. The aim of this study was to determine the effects of apixaban vs standard of care on post-TAVR valve thrombosis detected by 4-dimensional (4D) computed tomography.. The randomized ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis) trial demonstrated that apixaban 5 mg twice daily was not superior to standard of care (vitamin K antagonists or antiplatelet therapy) after successful TAVR and was associated with similar safety but with more noncardiovascular deaths. Three months after randomization, 4D computed tomography was proposed to all patients to determine the percentage of patients with ≥1 prosthetic valve leaflet with grade 3 or 4 reduced leaflet motion or grade 3 or 4 hypoattenuated leaflet thickening (the primary endpoint) in the intention-to-treat population.. Seven hundred sixty-two participants had complete multiphase datasets and were included in the 4D computed tomographic analysis. The primary endpoint occurred in 33 (8.9%) and 51 (13.0%) patients in the apixaban and standard-of-care groups, respectively. It was reduced with apixaban vs antiplatelet therapy (OR: 0.51; 95% CI: 0.30-0.86) but not vs vitamin K antagonists (OR: 1.80; 95% CI: 0.62-5.25) (P. Apixaban reduced subclinical obstructive valve thrombosis in the majority of patients who underwent TAVR without having an established indication for anticoagulation. This study was not powered for clinical outcomes. (Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis [ATLANTIS]; NCT02664649).

Topics: Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Fibrinolytic Agents; Four-Dimensional Computed Tomography; Heart Valve Prosthesis; Humans; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Risk Factors; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

Current guidelines recommend anticoagulation with a vitamin K antagonist to treat left ventricular (LV) thrombus after myocardial infarction (MI). Data on the use of direct oral anticoagulants (DOACs) in this setting are limited. The aim of the study was to assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI.. We conducted a prospective, randomized, multicentre open-label clinical trial including patients with LV thrombus detected by 2D transthoracic echocardiography 1-14 days after acute MI. Thirty-five patients were enrolled in three medical centres; 17 patients were randomized to warfarin and 18 patients to apixaban. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Secondary outcomes were major bleeding, stroke or systemic embolism, re-hospitalization, and all-cause mortality. Mean LV thrombus size at enrolment was 18.5 mm × 12.3 mm in the warfarin group and 19.9 mm × 12.4 mm in the apixaban group (P = NS). Thirty-two patients completed 3 months follow-up. In the warfarin group, two patients withdrew, and in the apixaban group one patient died. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 patients in the apixaban group (P = NS and P = 0.026 for non-inferiority). Two patients had major bleeding in the warfarin group, while no major bleeding events were recorded in the apixaban group. There was one stroke in the warfarin group and one death in the apixaban group.. Our results suggest that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI with a 20% non-inferiority margin.

Topics: Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Myocardial Infarction; Prospective Studies; Pyrazoles; Pyridones; Stroke; Thrombosis; Vitamin K; Warfarin

The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.. To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.. 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).. 6 university hospitals in Spain.. 190 adults (aged 18 to 75 years) with thrombotic APS.. Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).. The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.. After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.. Anticoagulation intensity was not measured in the rivaroxaban group.. Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.. Bayer Hispania.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.

Topics: Acenocoumarol; Adult; Anticoagulants; Elasticity; Factor Xa Inhibitors; Female; Fibrin; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Viscosity; Vitamin K; Warfarin

The coagulopathy of cirrhosis is complex, placing patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have equivalent or superior efficacy and safety as compared to vitamin K antagonists (VKAs); however, their efficacy and safety in liver cirrhosis has not been studied. To better define this, we evaluated outcomes of patients with cirrhosis prescribed DOACs compared to other anticoagulants at our center.. Retrospective cohort study of patients with cirrhosis prescribed therapeutic anticoagulation over a 3-year period for thrombosis or prevention of stroke in patients with atrial fibrillation. The primary outcomes of interest were bleeding events and recurrent thrombosis or stroke.. During the study period, 27 patients with cirrhosis were prescribed a DOAC and 18 were prescribed VKA or low molecular weight heparin (LMWH). Both groups had similar total bleeding events (8 DOAC vs 10 other, P=.12). There were significantly less major bleeding episodes in the DOAC group (1 [4%] vs 5 [28%], P=.03). Recurrent thrombosis occurred in one patient receiving a DOAC (4%) and one patient (6%) receiving other anticoagulation (P=1.0).. Direct oral anticoagulant use in patients with cirrhosis may be as safe as traditional anticoagulants. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or thrombosis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Stroke; Thrombosis; Vitamin K

Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by thrombosis, pregnancy morbidity, and the presence of characteristic antibodies. Current therapy for patients having APS with a history of thrombosis necessitates anticoagulation with the vitamin K antagonist warfarin, a challenging drug to manage. Apixaban, approved for the treatment and prevention of venous thrombosis with a low rate of bleeding observed, has never been studied among patients with APS.. We report study rationale and design of Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome (ASTRO-APS), a prospective randomized open-label blinded event pilot study that will randomize patients with a clinical diagnosis of APS receiving therapeutic anticoagulation to either adjusted-dose warfarin or apixaban 2.5 mg twice a day. We aim to report our ability to identify, recruit, randomize, and retain patients with APS randomized to apixaban compared with warfarin. We will report clinically important outcomes of thrombosis and bleeding. All clinical outcomes will be adjudicated by a panel blinded to the treatment arm. A unique aspect of this study is the enrollment of patients with an established clinical diagnosis of APS. Also unique is our use of electronic medical record interrogation techniques to identify patients who would likely meet our inclusion criteria and use of an electronic portal for follow-up visit data capture.. ASTRO-APS will be the largest prospective study to date comparing a direct oral anticoagulant with warfarin among patients with APS for the secondary prevention of thrombosis. Our inclusion criteria assure that outcomes obtained will be clinically applicable to the routine management of patients with APS receiving indefinite anticoagulation.

Topics: Administration, Oral; Adult; Antiphospholipid Syndrome; Female; Humans; Male; Middle Aged; Pilot Projects; Pregnancy; Pregnancy Complications, Hematologic; Pyrazoles; Pyridones; Thrombosis; Vitamin K; Warfarin

There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Blood Coagulation; Blood Platelets; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 Enzyme System; Dabigatran; Double-Blind Method; Electrodes; Female; Humans; Light; Male; Middle Aged; Nephelometry and Turbidimetry; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Thrombelastography; Thrombosis; Ticlopidine; Vitamin K

Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown.. Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA.. With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.

Topics: Aged; Atrial Fibrillation; Atrial Flutter; Atrial Function, Left; Dabigatran; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Vitamin K

Interindividual variations in dose requirements of oral vitamin K antagonists (VKA) are attributed to several factors, including genetic variant alleles of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9), but also interaction with co-medications. In this context, proton pump inhibitor (PPI)-related alterations of VKA maintenance dose requirements have been published. The present investigation aimed to test for an interaction profile of oral VKA-therapy and PPIs in relation to the CYP2C9 genotype. Median weekly stable VKA dose requirements over 1 year were recorded in 69 patients. Patients were genotyped for CYP2C9*2, CYP2C9*3, VKORC1c.-1639G>A and VKORC1c.174-136C>T and assessed for an association with PPI use and total VKA maintenance dose requirements. PPI users with CYP2C9 genetic variations required significantly lower weekly VKA maintenance doses than those with the wild-type genotype (t-test: P = 0·02). In contrast, in subjects without PPI use, the CYP2C9 genotype had no significant influence on oral VKA dose requirements. Further, the combined CYP2C9/VKORC1 genotype was a significant predictor for VKA dose requirements [linear regression: estimate: -1·47, standard error: 0·58 (P = 0·01)]. In conclusion, in carriers of CYP2C9 gene variations, the interference with the VKA metabolism is modified by PPI co-medication and the VCKORC1 genotype. Preceding knowledge of the genetic profile and the awareness for potentially occurring severe over-anticoagulation problems under PPI co-medication could contribute to a safer and personalized VKA pharmacotherapy.

Topics: Administration, Oral; Aged; Anticoagulants; Cytochrome P-450 CYP2C9; Female; Follow-Up Studies; Genotype; Humans; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors; Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

AZD0837 and ximelagatran are oral direct thrombin inhibitors that are rapidly absorbed and bioconverted to their active forms, AR-H067637 and melagatran, respectively. This study investigated the antithrombotic effect of AZD0837, compared to ximelagatran and the vitamin K antagonist (VKA) phenprocoumon (Marcoumar), in a disease model of thrombosis in patients with non-valvular atrial fibrillation (NVAF).. Open, parallel-group studies were performed in NVAF patients treated with VKA, which was stopped aiming for an international normalized ratio (INR) of ≤ 2 before randomization. Study I: 38 patients randomized to AZD0837 (150,250 or 350 mg) or ximelagatran 36 mg twice daily for 10-14 days. Study II: 27 patients randomized to AZD0837 250 mg twice daily or VKA titrated to an INR of 2-3 for 10-14 days. A control group of 20 healthy elderly subjects without NVAF or anticoagulant treatment was also studied. Size of thrombus formed on pig aorta strips was measured after a 5-minute perfusion at low shear rate with blood from the patient/control subject.. Thrombus formation was inhibited by AZD0837 and ximelagatran. Relative to untreated patients, a 50% reduction of thrombus size was estimated at plasma concentrations of 0.6 and 0.2 μmol/L for AR-H067637 and melagatran, respectively. For patients receiving VKA treatment, the thrombus size was about 15% lower compared with healthy elderly controls.. Effects of AZD0837 and ximelagatran on thrombus formation were similar or greater than for VKA therapy and correlated with plasma concentrations of their active forms.

Topics: Administration, Oral; Aged; Amidines; Animals; Anticoagulants; Antithrombins; Atrial Fibrillation; Azetidines; Benzylamines; Female; Humans; In Vitro Techniques; Male; Middle Aged; Swine; Thrombosis; Treatment Outcome; Vitamin K

Topics: Aged; Anticoagulants; Comorbidity; Female; Humans; Hypothyroidism; Male; Netherlands; Prevalence; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Vitamin K

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation Factors; Drug Interactions; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K; Warfarin

After a vitamin K antagonist (VKA) overdose, 1-2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range.. To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to < or = 1.5 before elective surgery.. Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day -5 before surgery (group H) or to VKA treatment until day -2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days -5/-2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC).. In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days -1 and 0 than in group H. An INR < or = 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients.. Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants.

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Chi-Square Distribution; Drug Administration Schedule; Elective Surgical Procedures; France; Hemoglobins; Heparin; Humans; International Normalized Ratio; Postoperative Hemorrhage; Preoperative Care; Surgical Procedures, Operative; Thrombosis; Time Factors; Vitamin K

We determine the efficacy of active reversal of warfarin anticoagulation with intravenous vitamin K compared to withholding warfarin in patients requiring urgent orthopedic trauma surgery.. This was a prospective cohort with immediate prehypothesis consecutive retrospective comparative case series conducted at a level 1 university hospital trauma unit.. Forty-eight consecutive patients between 1998 and 2004 in a study composed of a prospective cohort were compared with a retrospective consecutive case series of warfarinized orthopedic trauma patients requiring urgent surgery. The prospective arm directly followed the historic case series from which the hypothesis was generated.. Vitamin K administration.. Primary outcome was time to surgery. Secondary outcomes were problems with active reversal, length of time for warfarin stabilization after surgery, and complications.. The mean time to surgery in warfarinized patients not given vitamin K was 111.9 hours; in the intervention group, it was 67.4 hours, giving a mean difference of 44.5 hours (P = 0.01). Vitamin K reduced the international normalized ratio (INR) to less than 2.0 in 74% of patients within 24 hours. There were no complications of vitamin K administration. A dose of vitamin K costs approximately 1/1000 of a hospital bed day cost. A loading dose of warfarin on the second postoperative day took approximately 1 day longer to reach an INR of greater than 2.0 in the intervention patients than in those who had not been given vitamin K.. Warfarin reversal with vitamin K was successful and facilitated earlier surgery in all patients; the first dose was effective in approximately three quarters of patients. It is cost-effective, with no side effects caused in this study.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Cohort Studies; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Orthopedic Procedures; Preoperative Care; Thrombosis; Treatment Outcome; Vitamin K; Warfarin; Wounds and Injuries

Thrombin is a main mediator of arterial thrombus formation, and its inhibition is an important antithrombotic strategy. However, the place of vitamin K antagonists among the different therapeutic strategies for preventing arterial thrombus formation is still debated. We studied the antithrombotic efficacy of the vitamin K antagonist fluindione in a human ex vivo model of arterial thrombosis and determined whether aspirin enhances fluindione efficacy. Ten healthy male volunteers were randomly assigned to receive fluindione, alone or in combination with aspirin (325 mg/d). Fluindione was given at increasing doses to give a stable international normalized ratio (INR) between 1.5 and 2.0 and between 2.1 and 3.0. We induced arterial thrombus formation ex vivo by exposing collagen- or tissue factor (TF)-coated coverslips in a parallel-plate perfusion chamber to native blood for 3 minutes at an arterial wall shear rate of 2600 s(-1). Platelet and fibrin deposition were measured by immunoenzymatic methods. Fluindione inhibited thrombus formation on TF-coated coverslips in a dose-dependent manner by 50% and 80% at INR 1.5 to 2.0 and INR 2.1 to 3.0, respectively (P<0.05). Fluindione in combination with aspirin inhibited TF-induced thrombus formation in a comparable manner. Collagen-induced thrombus formation was not reduced in subjects treated by fluindione. It was reduced by 50% to 60% in those treated with fluindione plus aspirin, regardless of the level of anticoagulation (P<0.05). Thus, the effectiveness of fluindione for preventing arterial thrombosis is dependent on the nature of the thrombogenic trigger. Fluindione is very effective in preventing TF- but not collagen-triggered thrombus formation. Aspirin enhances the antithrombotic effectiveness of fluindione, because combined treatment interrupts both TF- and collagen-induced thrombus formation.

Topics: Adolescent; Adult; Anticoagulants; Aspirin; Collagen; Drug Synergism; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Male; Phenindione; Thromboplastin; Thrombosis; Vitamin K

Topics: Adenosine Diphosphate; Animals; Anticoagulants; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Clinical Trials as Topic; Cyclic AMP; Epinephrine; Fibrinolytic Agents; Heparin; Humans; Thrombin; Thrombosis; Vitamin K

Medical progress owes a great deal to the fundamental medical sciences and to the application of chemistry, physics and mathematics to medical problems. However, clinical observations and investigations are still of decisive importance in any field of medicine. By a feed-back mechanism they may even stimulate and fertilize fundamental medical sciences. Thus, our knowledge of the blood coagulation mechanism has been considerably enlarged by clinical analysis of hereditary bleeding disorders. - Chemotherapy of neoplastic diseases started from clinical observations during World War I (production of leucopenia by sulfur mustard gas). - Surgical procedures and their consequences have contributed greatly to our knowledge of thyroid function, of the segmental anatomy of the lung, and of the conduction system of the heart. - Observations of side effects of drugs have often enlarged or completely changed their primary clinical indications: from antibacterial sulfonamides, anti-diabetic, antihypertensive and powerful diuretic drugs have been developed, and from histaminics the modern neuroleptics and antidepressants. - Fundamental immunology has been enormously activated by clinical transplantation of kidney and bone marrow. Selective immunological defects in men, real experiments of nature, contributed much to our knowledge of the various types of allergic response. The quality of clinical investigations, particularly of controlled clinical trials, has been considerably improved during the last two decades. Although it is an applied science the reliability of its results is to-day comparable with that of "pure" natural sciences. However, medicine is more than a natural science: examples of outstanding scientists who at the same time were great and human physicians are presented.

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Arthritis; Cardiac Catheterization; Clinical Trials as Topic; Diabetes Mellitus; Dicumarol; Electroencephalography; Heart Conduction System; Humans; Research Design; Sulfonamides; Thrombosis; Thymus Gland; Thyroid Gland; Vitamin K

Natural product berberine was reported to inhibit platelet activation and thrombosis by suppressing the class Ⅰ PI3Kβ/Rasa3/Rap1 pathway. This study aims to investigate the effects and mechanisms of berberrubine, a main metabolite of berberine, to inhibit thrombus formation.. Carrageenan-induced mouse tail thrombosis model was used to evaluate the effects of berberrubine hydrochloride (BBB) on thrombus formation in vivo. Non-targeted metabolomics was performed with UPLC-Q-TOF/MS to explore the potential mechanisms of BBB in inhibiting thrombosis. The effects of BBB on bleeding risk and prothrombin time were determined. And molecular docking was used to identify the possible target of BBB.. After oral administration, BBB significantly inhibited carrageenan-induced thrombosis in mice without prolonging bleeding time. The results of non-targeted metabolomics showed that oral BBB could regulate 'Phenylalanine, tyrosine and tryptophan biosynthesis' and 'Ubiquinone and other terpenoid-quinone biosynthesis', which is closely related to the vitamin K catalytic cycle. Molecular docking revealed BBB could combine and interact with vitamin K epoxide reductase (VKOR) and γ-Glutamyl carboxylase (GGCX), which was mutually confirmed with the experimental results that oral BBB could significantly prolong prothrombin time.. Integrated metabolomics and molecular docking reveal BBB inhibited thrombosis by regulating the vitamin K catalytic cycle. Our research is helpful in deeply understanding the antithrombotic material basis of oral berberine, and also could provide scientific evidence for developing new antithrombotic drugs based on BBB in the future.

Topics: Animals; Berberine; Carrageenan; Fibrinolytic Agents; GTPase-Activating Proteins; Mice; Molecular Docking Simulation; Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Current guidelines recommend vitamin K antagonists (VKAs) for the treatment of a left ventricular thrombus (LVT). However, direct oral anticoagulants (DOACs) show superior safety and efficacy compared with VKAs in most thromboembolic disorders. Nevertheless, DOACs remain poorly investigated for the treatment of LVT. To describe the thrombus resolution rate and clinical efficacy of DOACs versus VKAs in patients with LVT, we analyzed consecutive patients with confirmed LVT from a multicenter echocardiography database. Echocardiograms and clinical end points were evaluated independently. The thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen. In total, 101 patients were included (17.8% women, mean age 63.3 ± 13.2 years), 50.5% had recently experienced a myocardial infarction. The mean left ventricular ejection fraction was 36.6 ± 12.2%. DOACs versus VKAs were used in 48 and 53 patients, respectively. The median follow-up was 26.6 (interquartile range 11.8;41.2) months. Among patients receiving VKAs compared with DOACs, the thrombus resolved more rapidly within the first month in those taking VKAs (p = 0.049). No differences were seen between the 2 groups with respect to major bleedings, strokes, and other thromboembolic events. In each group, LVT recurred in 3 of the subjects (a total of 6) after discontinuation of anticoagulation. In conclusion, DOACs appear to be a safe and effective alternative to VKAs for the treatment of LVTs, but the rate of thrombus dissolution within 1 month after initiation of anticoagulation appears to be higher with VKAs. A sufficiently powered randomized trial is required to definitively define the role of DOACs in the treatment of LVT.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Registries; Stroke Volume; Switzerland; Thromboembolism; Thrombosis; Ventricular Function, Left; Vitamin K

BACKGROUND Left ventricular thrombus is a serious complication of numerous cardiovascular conditions. Anticoagulation with oral vitamin K antagonists such as warfarin is a standard treatment for left ventricular thrombus and is recommended to reduce the risk of embolization. Patients with cardiac conditions share comorbidities with patients with end-stage renal disease, and patients with advanced kidney disease are predisposed to atherothrombotic and thromboembolic complications. The efficacy of direct oral anticoagulants in patients with left ventricular thrombus has not been well studied. CASE REPORT A 50-year-old man had prior myocardial infarction, heart failure with reduced ejection fraction, diabetes, hypertension, atrial fibrillation, treated hepatitis B infection, and end-stage renal disease on hemodialysis. On regular outpatient follow-up with the cardiology clinic, a transthoracic echocardiogram was requested and revealed akinesia of the mid to apical anterior wall, mid to apical septum, and left ventricular apex, and large apical thrombus measuring 20×15 mm. Apixaban 5 mg orally twice daily was started. A transthoracic echocardiogram was done after 3 months and after 6 months, and the thrombus did not resolve. The apixaban was shifted to warfarin. The international normalized range was maintained at the therapeutic range (INR 2.0-3.0). After 4 months of receiving warfarin, echocardiography showed a resolution of the left ventricular thrombus. CONCLUSIONS We report a case of left ventricular thrombus that was successfully dissolved by warfarin after treatment with apixaban failed. This case challenges the general assumption of apixaban's effectiveness in patients with end-stage renal disease on dialysis.

Topics: Anticoagulants; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Thrombosis; Vitamin K; Warfarin

Meta-analysis may increase the risk of random errors. Trial sequential analysis (TSA) has been developed to adjust for these random errors. We conducted TSA on the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in left ventricular thrombus (LVT) patients in order to estimate how many additional patients should be required to draw definite conclusions. PubMed, Scopus, and Cochrane Library databases were searched for articles directly comparing DOACs and VKAs for LVT in LV thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, and all-cause death. TSA was conducted with a cumulative Z-curve, monitoring boundaries, and required sample size. A simulated trial was run and TSA estimated the sample sizes of trials needed to draw definite conclusions. Of 4749 articles, 25 studies were used for the analysis. TSA revealed the current sample size already demonstrated superiority of DOACs in LV thrombus resolution and stroke, and futility in any thromboembolism and all-cause death. Two other outcomes did not achieve the required sample size. The sample size of new trials needed to demonstrate the superiority of DOACs over VKAs was estimated 400 for any bleeding. Corresponding trials needed to demonstrate no significant differences could be estimated for major bleeding and any bleeding (n = 200 and n = 2000, respectively). Current results show that the sample size required to draw definite conclusions was not reached for two outcomes, and there was a risk of random error. Further randomized controlled trials with sample sizes estimated by TSA will work effectively to obtain valid conclusions.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Meta-Analysis as Topic; Stroke; Thromboembolism; Thrombosis; Vitamin K

To assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE).. All children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models.. We included 405 patients. Median follow-up was 18.7 (9.3-49.4) months. The median TTR was 83.1 % (74.4 %-95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1-1.8]) and 2.3 % (CI95 % [0.9-3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %-99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2-8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6-11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5-15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9-32.0], p = 0.005) was the only risk factor for thrombotic events.. Overall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.

Topics: Anticoagulants; Atrial Fibrillation; Child; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; Prospective Studies; Risk Factors; Thrombosis; Vitamin K

Left ventricular thrombi form due to the presence of Virchow's triad in patients with left ventricular systolic dysfunction. This complication increases the incidence of systemic embolization, hence anticoagulation is recommended to decrease this risk. Up to the present time, vitamin K antagonists are recommended by all societal guidelines for patients with left ventricular thrombi. Recently, several studies have investigated the role of different anticoagulants and yielded promising outcomes. This opinion article focuses on the evidence supporting vitamin K antagonists and direct oral anticoagulants in patients with left ventricular thrombi.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Thrombosis; Ventricular Dysfunction, Left; Vitamin K

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risks. Among possible valuable answers, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: (1) multiparametric assessment of thrombotic and bleeding risks based on patients' individual and surgical risk factor, (2) testing of prothrombin time, activated partial thromboplastin time, and DOAC plasma levels before surgery or invasive procedure, (3) use of heparin, (4) restarting of full-dose DOAC after high risk bleeding surgery, (5) practical nonpharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary "anticoagulation team" with the aim to define the optimal perioperative management of anticoagulation.

Topics: Anticoagulants; Antithrombins; Elective Surgical Procedures; Hematologic Tests; Humans; Italy; Patient Care Management; Perioperative Care; Postoperative Hemorrhage; Risk Adjustment; Thrombosis; Vitamin K

This retrospective observational study was conducted from 2010 to 2019 in National Center of Cardiovascular Diseases of China. We included patients with VT confirmed by imaging. The primary outcome was the rate of thrombus resolution. Hazard ratio (HR) was calculated with or without adjustment for covariates using Cox proportional hazards regression models.. 463 patients were included. 43.0% received VKAs, 16.6% received NOACs, and 40.4% received APT. Over a median of 468 days' follow-up, NOACs group was more likely to have the thrombus resolved within 12 months' follow-up than VKAs (HR 2.28, 95% CI 1.57 to 3.31) or APT (HR 2.92, 95% CI 1.97 to 4.33). After adjustment for baseline variables, the significance remained in the comparison of NOACs versus VKAs (HR 2.13, 95% CI 1.41 to 3.22) as well as NOACs versus APT (HR 2.55, 95% CI 1.53 to 4.27). No significant differences were identified in bleeding rate, thromboembolism rate, or all-cause death in 12 months' follow-up.. Our findings showed that patients who were male, diagnosed with MI with or without ventricular aneurysm, or diagnosed with coronary artery diseases medical history had a risk of thrombus unresolved. Patients with NOACs had a higher resolution and a similar safety profile comparing VKAs or APT, which persisted after adjusting for other factors. Large randomized controlled trials are required urgently. This trial is registered with NCT05006677.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Risk Factors; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Cerebral Veins; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Therapeutic anticoagulation with either a vitamin K antagonist (VKA) or direct anticoagulant (DOAC) is often newly prescribed to patients undergoing lower extremity bypass (LEB) to aid in graft patency when risk factors for thrombosis are present or to treat postoperative venous thromboembolism or atrial fibrillation. There is a gap in knowledge as to how DOAC usage impacts postoperative outcomes compared with the standard-of-care VKAs.. To determine temporal trends in DOAC prescription after infrainguinal LEB, impact on length of stay (LOS), and associated bleeding and thrombotic complications, patients undergoing elective LEB were identified from the Vascular Quality Initiative between January 2013 and May 2019. Postoperative bleeding, LOS, and graft occlusion for patients receiving VKA compared with DOAC were evaluated.. A total of 24,459 LEBs were performed during the study period. Among 2,656 patients newly prescribed an anticoagulant, 78.0% (n = 2,072) received VKA and 22.0% (n = 584) received a DOAC, with DOAC use increasing throughout the study period. There was no significant difference in postoperative bleeding (VKA 2.3%, DOAC 1.7%, p = 0.413) or graft occlusion (VKA 1.2%, DOAC 1.4%, p = 0.762) between the anticoagulant classes. LOS was shorter in the DOAC group than in the VKA group (5.7 vs 6.8 days; p < 0.001).. This analysis demonstrates that DOAC use is increasing with time in Vascular Quality Initiative centers. DOACs are a safe and comparable alternative to VKAs in the postoperative setting with similar rates of bleeding complications and early graft patency and are associated with a reduced postoperative LOS.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Lower Extremity; Thrombosis; Vitamin K

Topics: Anticoagulants; Heart Diseases; Humans; Off-Label Use; Thrombosis; Vitamin K

The objectives of this retrospective cohort study were to examine the effect of vitamin K administration on hemorrhagic and thrombotic complications, blood product utilization, and outcomes in neonatal extracorporeal membrane oxygenation (ECMO).. In the pilot study, complications, blood product use, and outcome data for neonates who received (. In the pilot study, vitamin K at ECMO initiation was associated with fewer thrombotic complications and similar hemorrhagic complications. The volume of fresh frozen plasma was higher in neonates who received vitamin K, but total blood product and other component volume did not differ between groups. ECMO run time, survival off ECMO, survival to discharge, and length of stay did not differ between cohorts. In the validation cohort, neonates who received additional vitamin K during ECMO had longer ECMO run time and length of stay, but no difference in mortality was observed. Further, thrombotic and hemorrhagic complications as well as blood product exposure were similar between cohorts.. These data suggest that routine vitamin K administration may have limited or no benefit during neonatal ECMO.

Topics: Extracorporeal Membrane Oxygenation; Humans; Hypoxia; Infant, Newborn; Pilot Projects; Respiratory Insufficiency; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

Left ventricular thrombus (LVT) can complicate ST-Elevation myocardial infarction (STEMI) and is associated with poor outcomes. Conventional triple anticoagulation [Vitamin K Antagonists (VKA) plus dual-antiplatelet therapy (DAPT)] is the first-line therapy for LVT after STEMI. In patients with LVT following STEMI, contemporary data of triple therapy with rivaroxaban are lacking.. We conducted a retrospective cohort study involving 1335 STEMI patients who underwent primary percutaneous coronary intervention (PCI). Among patients who developed LVT after STEMI, we observed differences in efficacy between rivaroxaban plus DAPT therapy and VKA plus DAPT. The time of LVT resolution was also evaluated, as well as net clinical adverse events, and rates of bleeding events.. In 1335 patients with STEMI, a total of 77 (5.7%) developed LVT over the follow-up period (median 25.0 months). Of the patients diagnosed with LVT, 31 patients were started on triple therapy with VKA, 33 patients on triple therapy with rivaroxaban. There was a consistent similarity in LVT resolution with rivaroxaban application compared to VKA application during the follow-up period [HR (log-rank test) 1.57(95% CI 0.89-2.77), p = 0.096; Adjusted HR 1.70(95% CI 0.90-3.22), p = 0.104]. Triple therapy with rivaroxaban showed quicker resolution than with VKA (6 months: p = 0.049; 12 months: p = 0.044; 18 months: p = 0.045). Similar risks of ISTH bleeding were not significantly different between the 2 groups [VKA 9.7% vs Rivaroxaban 6.1%, Adjusted HR 0.48 (95% CI 0.73-3.20); p = 0.444)]. Fewer net adverse clinical events (NACE) were observed in the rivaroxaban group [VKA 58.1% vs Rivaroxaban 24.2%; HR (log-rank test) 0.31(95% CI 0.14-0.68), p = 0.003; Adjusted HR 0.23(95% CI 0.09-0.57), p = 0.001].. In the observational study, triple therapy with rivaroxaban has similar and quicker LVT resolution in patients with LVT after STEMI, compared with triple therapy with VKA, and perhaps was associated with a better clinical benefit. Larger sample sizes and randomized controlled trials are needed to confirm this observation.

Topics: Anticoagulants; Humans; Percutaneous Coronary Intervention; Retrospective Studies; Rivaroxaban; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome; Vitamin K; Warfarin

The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates.. This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events.. The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008).. In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.

Topics: Anticoagulants; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Portal Vein; Retrospective Studies; Thrombosis; Venous Thrombosis; Vitamin K

A retrospective cohort study was conducted to compare the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in the treatment of patients with left ventricular thrombus (LVT).. Consecutive patients admitted to our institution with LVT between February 2009 and December 2020 and treated with either DOACs or VKAs were considered for inclusion in this study. The outcomes included stroke or systemic embolism (SSE), thrombus resolution, and bleeding events.. Eighty-seven patients with LVT were identified. Of these, 25 patients were treated with DOACs and 62 patients were treated with VKA. The average follow-up period was 2.37±2.1 years. DOACs were associated with similar incidences of stroke (4.0% vs. 4.8%; P=0.158), systemic embolism (0% vs. 1.6%; P=0.906), SSE (4.0% vs. 6.5%; P=0.657), thrombus resolution (76.0% vs. 74.2%; P=0.057), and blooding events (4.0% vs. 3.2%; P=0.858) as compared to VKAs. In the univariate logistic regression analysis, there was a significant difference between the DOAC and VKA groups in the incidence of SSE when antiplatelets were controlled [odds ratio (OR) =0.34, 95% confidence interval (CI): 0.21, 0.98; P=0.027]. However, in the multivariate analysis, antiplatelets had no significant effect on the outcome (OR =0.41, 95% CI: 0.36, 1.54; P=0.366).. DOACs had similar efficacy and safety to VKAs in the treatment of patients with LVT. Randomized controlled trials should be conducted to verify our findings.

Topics: Administration, Oral; Anticoagulants; Humans; Retrospective Studies; Thrombosis; Vitamin K

Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death.. We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported.. The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.

Topics: Adult; Aged; Anticoagulants; Catheterization, Central Venous; Conservative Treatment; Female; Fibrinolytic Agents; Heart Atria; Heart Diseases; Humans; Male; Middle Aged; Renal Dialysis; Thrombosis; Treatment Outcome; Urokinase-Type Plasminogen Activator; Vitamin K

Current guidelines recommend the use of vitamin K antagonist (VKA) for up to 3-6 months for treatment of left ventricular (LV) thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of novel oral anticoagulants (NOAC) compared to VKA for other indications such as deep vein thrombosis, pulmonary embolism (PE), and thromboembolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post-AMI. In this study, we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI.. This was an observational study of 2328 consecutive patients undergoing coronary angiography ± percutaneous coronary intervention (PCI) for AMI between May 2015 and December 2018, at a UK cardiac centre. Patients' details were collected from the hospital electronic database. The primary endpoint was rate of LV thrombus resolution with bleeding rates a secondary outcome. Left ventricular thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban: 36.5%, and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (previous myocardial infarction, PCI, coronary artery bypass grafting), and cardiovascular risk factors (hypertension, diabetes, hypercholesterolaemia). Over the follow-up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs. 64.4%, P = 0.0018, at 1 year), which persisted after adjusting for baseline variables (odds ratio 1.8, 95% confidence interval 1.2-2.9). Major bleeding events during the follow-up period were lower in the NOAC group, compared with VKA group (0% vs. 6.7%, P = 0.030) with no difference in rates of systemic thromboembolism (5% vs. 2.4%, P = 0.388).. These data suggest improved thrombus resolution in post-acute coronary syndrome (ACS) LV thrombosis in patients treated with NOACs compared to VKAs. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients vs. VKA-treated patients. Thus, provides data to support a randomized trial to answer this question.

Topics: Administration, Oral; Anticoagulants; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Thrombosis; Vitamin K; Warfarin

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.

Topics: Calcium-Binding Proteins; COVID-19; Extracellular Matrix Proteins; Humans; Lung; Matrix Gla Protein; Protein S; SARS-CoV-2; Thromboembolism; Thrombosis; Vitamin K; Vitamin K Deficiency

Primary antiphospholipid syndrome (PAPS) is a chronic autoimmune disorder clinically characterized by thromboembolic events or obstetric complications. Prolonged anticoagulation therapy with vitamin K antagonists (VKA) is the treatment of choice for PAPS patients with thrombosis. However, the efficacy of VKA therapy depends on laboratory monitoring, dose adjustment, adequate lifestyle and adherence to treatment. Difficulties with VKA therapy can affect patients' self-perceived health related quality of life (HRQOL). This study aims to evaluate PAPS patients' HRQOL, therapy adherence and knowledge of treatment.. A general Medical Outcome Study Short Form-36 (SF-36) and the Duke Anticoagulation Satisfaction Scale (DASS) were used to access APS-patients self-perceived HRQOL. Treatment adherence was measured by the Treatment Measure Adhesion (TMA) - oral anticoagulant version instrument, and knowledge of VKA treatment was measured using the MedTake test.. 66 PAPS patients using VKA were assessed. 63% of them were female; the mean age was 41.9 years old, approximately 60% had unprovoked venous thrombosis and one third of the patients had recurrent thrombotic events. The most impacted domain of DASS was "psychological impacts" and the factors associated to anticoagulation related poor HRQOL were: female sex, presence of arterial thrombosis and INR lability. Using the SF-36 instrument, PAPS-patients self-perceived HRQOL was poorer than that of the general Brazilian population and was associated with female sex and presence of cardiovascular risk factors.. Despite the high adherence to treatment and knowledge of VKA therapy, self-perceived HRQOL is poor in patients with PAPS and is mainly affected by VKA therapy. Searching for better treatment options is warranted.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Brazil; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Quality of Life; Self Concept; Surveys and Questionnaires; Thromboembolism; Thrombosis; Treatment Adherence and Compliance; Vitamin K

Patient's adherence to oral anticoagulant therapy is essential to prevent and treat thrombotic events.. To assess the patients' adherence Morisky Medication Adherence Scale 8-items was used. The target population included 785 consecutive outpatients, of whom 384 were on Vitamin K Antagonists and 401 on Direct Oral Anticoagulants. Moreover, we evaluate which variable among age, gender, having experienced a thrombotic episode, time in the therapeutic range for patients on Vitamin K Antagonists, being naive and once versus twice daily drug assumption for patients on Direct Oral Anticoagulants, could affect adherence to therapy.. Morisky Medication Adherence Scale 8-items score was 8 in both groups. The intentional non-adherence obtained the lowest score while the unintentional non-adherence is the most frequent problem in patients treated with either Vitamin K Antagonists or Direct Oral Anticoagulants. Age > 75 years, male gender, having experienced a thrombotic episode, being naive and assuming Direct Oral Anticoagulants twice a day were significantly associated with a higher risk to forget assuming the oral anticoagulant, to have more difficulty in remembering to take it or to bring it in case of travel or leaving home. A low percentage of time in therapeutic range was associated with a not regularly assumption of the anticoagulants.. Patients treated with Vitamin K Antagonists or Direct Oral Anticoagulants show a good adherence and persistence to their oral anticoagulant therapy. Several factors have been identified to affect patients' adherence and deserve a careful attention by the doctors at the Anticoagulation Clinic.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Male; Medication Adherence; Thrombosis; Vitamin K

Topics: COVID-19; COVID-19 Vaccines; History, 20th Century; Humans; Pesticides; Public Health; Risk Factors; Thrombosis; Vitamin K

The target ranges (TR) for anticoagulation with vitamin K antagonists (VKA) in the Netherlands were changed in 2016 from INR 2.0-3.5 ('low intensity') and INR 2.5-4.0 ('high intensity') to INR 2.0-3.0 and INR 2.5-3.5, respectively.. To assess the effect of the TR change on therapeutic quality control (TQC) in a Dutch regional thrombosis center taking care of approximately 3600-5500 patients annually.. TQC of chronically treated patients was assessed as the average time in therapeutic range (TTR). Evaluations were performed for non-self-management (NSM), as well as self-management patients. INR percentiles were assessed from all INR determinations in all patients, i.e. including those of induction episodes and patients treated for a short-term.. The number of NSM patients treated chronically decreased gradually, while their average age increased, with a marginal but significant gradual increase in bleeding complications. In the period 2011-2015, i.e. before the TR change, there was a gradual increase of the TTR in NSM patients from 77.5% to 88.9% (low intensity) and from 75.3% to 84.1% (high intensity). In the same period, the median INR of all patients in the low and high intensity ranges decreased from 2.9 to 2.7, and from 3.3 to 3.2, respectively. The TTR in self-management patients remained virtually constant. After TR changes from 2016 on, the TTR of all NSM patients in the low and high intensity groups decreased to 77% and 70%, respectively, and median INRs decreased to 2.6 and 3.0, respectively.. Introduction of internationally harmonized target ranges in 2016 resulted in further lowering of median INR values in both target ranges. As expected, TTR was reduced slightly. These findings, together with a slight increase in average age and concomitant bleeding complications, suggest that the patients on long-term VKA treatment will require intensified monitoring and treatment.

Topics: Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Netherlands; Quality Control; Thrombosis; Vitamin K

Topics: Anticoagulants; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

It has recently been hypothesized that vitamin K could play a role in COVID-19. We aimed to test the hypotheses that low vitamin K status is a common characteristic of patients hospitalized with COVID-19 compared to population controls and that low vitamin K status predicts mortality in COVID-19 patients. In a cohort of 138 COVID-19 patients and 138 population controls, we measured plasma dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which reflects the functional vitamin K status in peripheral tissue. Forty-three patients died within 90 days from admission. In patients, levels of dp-ucMGP differed significantly between survivors (mean 877; 95% CI: 778; 995) and non-survivors (mean 1445; 95% CI: 1148; 1820). Furthermore, levels of dp-ucMGP (pmol/L) were considerably higher in patients (mean 1022; 95% CI: 912; 1151) compared to controls (mean 509; 95% CI: 485; 540). Cox regression survival analysis showed that increasing levels of dp-ucMGP (reflecting low vitamin K status) were associated with higher mortality risk (sex- and age-adjusted hazard ratio per doubling of dp-ucMGP was 1.49, 95% CI: 1.03; 2.24). The association attenuated and became statistically insignificant after adjustment for co-morbidities (sex, age, CVD, diabetes, BMI, and eGFR adjusted hazard ratio per doubling of dp-ucMGP was 1.22, 95% CI: 0.82; 1.80). In conclusion, we found that low vitamin K status was associated with mortality in patients with COVID-19 in sex- and age-adjusted analyses, but not in analyses additionally adjusted for co-morbidities. Randomized clinical trials would be needed to clarify a potential role, if any, of vitamin K in the course of COVID-19.

Topics: Adult; Aged; Biomarkers; Blood Coagulation; Calcium-Binding Proteins; Cohort Studies; COVID-19; Extracellular Matrix Proteins; Female; Hospital Mortality; Hospitalization; Humans; Male; Matrix Gla Protein; Middle Aged; Proportional Hazards Models; Regression Analysis; SARS-CoV-2; Thrombosis; Vitamin K; Vitamin K Deficiency; Young Adult

To investigate treatment modalities for children with extremity indwelling catheter (EIC)- or cardiac catheter-related arterial thrombosis.. The treatment of consecutive cases of catheter-related arterial thrombosis (CAT) at our institution between 2002 and 2017 was analyzed retrospectively.. A total of 242 CATs developed in 224 children. Of these, 125 (52%) were EIC-related and 117 (48%) were cardiac catheter-related. Treatment included heparin alone in 60 cases (25%), acetylsalicyclic acid (ASA) alone in 6 cases (2%), heparin followed by ASA in 171 cases (71%), heparin followed by vitamin K antagonist (VKA) in 4 cases (1.5%), and VKA alone in 1 case (0.5%). Complete resolution of CAT was observed in 173 cases (71.5%), partial resolution in 13 cases (5.4%), and no resolution in 56 cases (23.1%). No statistical significance in the resolution rate was observed between treatment groups (P = .23). In 66% of cases, complete resolution occurred at a median of 18 days (range, 4-44 days) with heparin alone. A switch from heparin to ASA in children with partial or no resolution of CAT did not increase the resolution rate at follow-up.. Heparin is an efficient treatment modality for CAT in pediatric patients. Long-term, subsequent treatment with ASA does not increase the resolution rate.

Topics: Adolescent; Anticoagulants; Aspirin; Cardiac Catheterization; Catheters, Indwelling; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Female; Femoral Artery; Fibrinolytic Agents; Follow-Up Studies; Heparin; Humans; Iliac Artery; Infant; Infant, Newborn; Male; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

The efficacy of direct oral anticoagulants (DOACs) in the management of left ventricular (LV) thrombi remains to be determined, especially in patients with ischemic cardiomyopathy. This retrospective study sought to compare the efficacy of vitamin K antagonists (VKAs) and DOACs in patients with LV thrombi and evaluate the rate of LV thrombus resolution after adjusting anticoagulation.. This observational retrospective study included patients admitted to our institution for LV thrombus between January 2010 and August 2019. The rate of LV thrombus resolution was compared between VKAs and DOACs. Patients without thrombus resolution with DOAC treatment were switched to VKA agents in order to obtain an international normalized ratio (INR) of 3-4.. Between January 2010 and August 2019, 59 consecutive patients with LV thrombi detected by transthoracic echocardiography were included in the study. The mean age was 62 ± 14 years and 16.9% were women. The circumstances of LV thrombus discovery were as follows: acute myocardial infarction or ischemic myocardiopathy (n = 22), stroke (n = 6), chest pain (n = 7), heart failure (n = 11), transthoracic echocardiographic evaluation (n = 11), and ventricular arrhythmias (n = 2). The proportion of patients on DOACs was 28.8% (n = 17), while that of those on VKAs was 71.2% (n = 42). Thrombus resolution was obtained in 70.6% (12/17) of patients on DOACs and in 71.4% (30/42) of those on VKAs (p = 0.9). Patients who failed to respond to DOAC treatment were treated with VKAs, and following this treatment adjustment all LV thrombi were dissolved in the DOAC group (5/5). Five embolic events (8.4% of stroke) occurred before the treatment initiation and six with anticoagulants (2/17 with DOACs [11.8%] and 4/42 with VKAs [9.5%]; p = 0.8).. This retrospective observational study found a similar efficacy between DOAC and VKA agents in patients with LV thrombi (70.6% vs. 71.5%); however, when the thrombus remains, VKAs are still the standard of care as it is possible to control INR levels (3-4) with them.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Arrhythmias, Cardiac; Female; Fibrinolytic Agents; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Stroke; Thrombosis; Vitamin K

Topics: Arabidopsis Proteins; Asbestos; Blood Platelets; Congresses as Topic; Construction Materials; Germany; Humans; Pseudopodia; Pulmonary Embolism; Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Left ventricular (LV) thrombus is increasingly detected in patients with and without ischaemic heart disease due to the increased availability of cardiac magnetic resonance imaging. Risk factors include anterior ST elevation myocardial infarction, delayed reperfusion therapy, and non-ischaemic cardiomyopathy with severe LV systolic dysfunction. We aimed to report the characteristics and outcomes of patients with LV thrombus treated with either vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC) with a view to describing differences in efficacy, specifically, subsequent thromboembolic events, thrombus resolution, and also side effects of therapy including clinically significant bleeding.. We conducted a retrospective, observational cohort study of patients diagnosed with LV thrombus between 1 December 2012 and 30 June 2018 and treated with either DOAC or VKA. We recorded patient demographics, past medical history, prescribed medications, and baseline investigations. The primary outcomes were rates of thromboembolism and clinically significant bleeding, with secondary outcomes of thrombus resolution on repeat cardiac imaging, repeat hospitalization, and all-cause mortality. During the study period, 84 patients were diagnosed with and managed for LV thrombus. Of these, 62 received VKA and 22 DOAC including 13 prescribed rivaroxaban, eight apixaban, and one dabigatran. Most patients 75 (89%) were male with an average age of 62 ± 14 years. Ischaemic heart disease was the cause of LV impairment in 73 (87%) patients. Baseline characteristics were similar between groups at baseline. Most n = 55 (65%) were co-prescribed a single antiplatelet agent and 32 (38%) received dual-antiplatelet therapy. During an average follow-up of 3.0 ± 1.4 years, there were no statistically significant differences between VKA and DOAC in rates of stroke (2% vs. 0%, P = 0.55), other thromboemboli (2% vs. 0%, P = 0.55), or clinically significant bleeding (10% vs. 0%, P = 0.13). The average interval to cardiac imaging follow-up was 233 ± 251 days and was not different between groups (P = 0.83), and there was no difference in the rate of resolution of thrombus (76% vs. 65% P = 0.33). Rehospitalization (50% vs. 45%: P = 0.53) and all-cause mortality (10% vs. 14%; P = 0.61) were also similar.. Our data suggest that DOACs are likely to be at least as effective and safe as VKA for stroke prevention in patients with LV thrombus and, despite their lack of a licence for this indication, are therefore likely to represent a reasonable and more convenient option for this setting. The optimal timing and type of anticoagulation for LV thrombus, as well as the role of screening for high-risk patients, should be tested in prospective, randomized trials.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Humans; Male; Middle Aged; Prospective Studies; Retrospective Studies; Thrombosis; Vitamin K

Topics: Cardiovascular Diseases; Fibrinolytic Agents; Germany; Humans; Patient Care Team; Randomized Controlled Trials as Topic; Thrombosis; Vitamin K

Vitamin K-Antagonists (VKAs) are the treatment of choice in patients with indications other than atrial fibrillation and venous thromboembolism. Moreover, some patients still assume VKAs refusing to change their therapy when direct oral anticoagulants (DOACs) are properly indicated. The COVID-19 pandemic has completely changed our lives, nullifying inter-personal relationships to avoid contagion, making difficult the VKAs monitoring. We describe the re-organization of our thrombosis centre (TC) as an example on how to face the emergency due to the COVID-19 pandemic. In the first phase, to avoid overcrowding at the TC, we planned to increase the interval time between INRs checks and to encourage blood sampling at home, especially for elderly patients. Moreover, precise scheduled blood sampling was also organized while telephone and email counselling were guaranteed by two doctors of the TC. In the second phase, to reduce the number of patients who daily attended our TC a switch from VKAs to DOACs was carried out, if no contraindications were identified. In the third phase, to protect patients, healthcare staff and hospital from COVID-19 widespread, telemedicine was strengthened. We tried to extend self-testing at home by means of portable coagulometers to as more patients as possible. To avoid patients staying or coming back to the TC an ad hoc web platform for sending the therapeutic dose adjustment and the next scheduled appointment was developed. The TC re-organization allowed us to monitor anticoagulated patients respecting personal isolation and security measures to avoid possible COVID-19 contagion.

Topics: Blood Coagulation; Coronavirus Infections; COVID-19; Humans; Italy; Pandemics; Pneumonia, Viral; Thrombosis; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

The proportion and characteristics of Italian patients affected by venous thromboembolism (VTE) treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), and complications occurring during follow-up.. A prospective cohort of 2728 VTE patients included in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) from January 2014 to June 2018 was investigated. Characteristics of patients, type of treatment and complications occurring during 2962 years of follow-up were analysed.. About 60 Italian anticoagulation and thrombosis centres participated in the observational START2-Register PARTICIPANTS: 2728 adult patients with VTE of a lower limb and/or pulmonary embolism (PE), with a follow-up after the initial phase treatment.. Patients could receive DOACs or VKAs; both prescribed by the National and Regional Health Systems for patients with VTE.. Efficacy: rate of VTE recurrence (all thrombotic complications were also recorded).. the rate of major and clinically relevant non-major bleeding events.. Almost 80% of patients were treated with DOACs. The prevalence of symptomatic PE and impaired renal function was higher in patients receiving VKAs. Duration of anticoagulation was >180 days in approximately 70% of patients. Bleeding events were similar in both treatment groups. The overall eventuality of recurrence was significantly higher in DOAC cohorts versus VKA cohorts (HR 2.15 (1.14-4.06), p=0.018); the difference was almost completely due to recurrences occurring during extended treatment (2.73% DOAC vs 0.49% VKA, p<0.0001). All-cause mortality was higher in VKA-treated (5.9%) than in DOAC-treated patients (2.6%, p<0.001).. Italian centres treat most patients with VTE with DOACs and prefer VKA for those with more serious clinical conditions. Recurrences were significantly more frequent in DOAC-treated patients due to increased incidence after 180 days of treatment, probably due to reduced adherence to treatment. These results underline the importance of structured surveillance of DOAC-treated patients with VTE to strengthen treatment adherence during extended therapy.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Male; Prospective Studies; Thrombosis; Venous Thromboembolism; Vitamin K

Covid-19, caused by SARS-CoV-2, has major world-wide health-related and socio-economic consequences. There are large disparities in the burden of Covid-19 with an apparent lower risk of poor outcomes in East Asians compared to populations in the West. A recent study suggested that Covid-19 leads to a severe extrahepatic vitamin K insufficiency, which could lead to impaired activation of extrahepatic proteins like endothelial anticoagulant protein S in the presence of normal hepatic procoagulant activity. This would be compatible with the enhanced thrombogenicity in severe Covid-19. The same study showed that vitamin K antagonists (VKA) that inhibit vitamin K recycling, had a greater impact on procoagulant activity than on the activation of extrahepatic vitamin K-dependent proteins during SARS-CoV-2 infections. A genetic polymorphism in the vitamin K epoxide reductase complex 1, VKORC1 -1639A, is particularly prevalent in East Asia and associates with low vitamin K recycling rates. Carriage of the allele may be regarded as bioequivalent to low-dose VKA use. We speculate that VKORC1 -1639A confers protection against thrombotic complications of Covid-19 and that differences in its allele frequency are partially responsible for the differences in Covid-19 severity between East and West.

Topics: Americas; Asia, Eastern; COVID-19; Europe; Gene Frequency; Humans; Models, Biological; Pandemics; Polymorphism, Single Nucleotide; SARS-CoV-2; Severity of Illness Index; Thrombosis; Vitamin K; Vitamin K Deficiency; Vitamin K Epoxide Reductases

The lack of quality control for patient point-of-care (POC) INR devices is an issue that has led the French health authorities to make recommendations: a laboratory INR (lab INR) has to be performed at the same time as the POC INR every 6 months. However, the differences observed between the two INRs, POC and lab INRs, are not necessarily due to a failure of the POC INR device. We present here a review of the different causes of discrepancies between INR results, which are the basis of the proposals of the Groupe français d'études sur l'hémostase et la thrombose (GFHT) on the management of lab and POC INR discrepancies. Pre-analytical conditions may account for discrepancies (sampling, transport and storage conditions), as well as analytical factors (mainly the nature of the thromboplastin used) and the clinical context (inflammatory or autoimmune diseases, polycythaemia...). The interpretation of INR discrepancies is not always easy and these proposals aim at standardizing the procedure to be followed in order to make the most appropriate decision for the patient.

Topics: 4-Hydroxycoumarins; Anticoagulants; Clinical Laboratory Techniques; France; Humans; Indenes; International Normalized Ratio; Laboratories; Laboratory Proficiency Testing; Reagent Kits, Diagnostic; Reference Standards; Reproducibility of Results; Self-Testing; Sensitivity and Specificity; Societies, Scientific; Thrombosis; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Thrombosis; Vitamin K

Complete graft thrombosis is the leading cause of early graft loss following pancreas transplantation. Partial thrombosis is usually subclinical and discovered on routine imaging. Treatment options may vary in such cases. We describe the incidence and relevance of partial graft thrombosis in a large transplant center. All consecutive pancreas transplantation at our center (2004-2015) were included in this study. Radiological follow-up, type and quantity of thrombosis prophylaxis, complications and, graft and patient survival were collected. Partial thrombosis and follow-up were also studied. All 230 pancreas transplantations were included in the analysis. Computed tomography was performed in most cases (89.1%). Early graft failure occurred in 23 patients (13/23 due to graft thrombosis, 3/23 bleeding, 1/23 anastomotic leakage, 6/23 secondary to antibody mediated rejection). There was evidence of partial thrombosis in 59 cases (26%), of which the majority was treated with heparin and a vitamin K antagonist with graft preservation in 57/59 patients (97%). Thrombosis is the leading cause of early graft loss following pancreas transplantation. Computed tomography allows for early detection of partial thrombosis, which is usually subclinical. Partial graft thrombosis occurs in about 25% of all cases. In this series, treatment with anticoagulant therapy (heparin and vitamin K antagonist) resulted in graft preservation in almost all cases.

Topics: Adult; Female; Graft Rejection; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pancreas Transplantation; Postoperative Complications; Retrospective Studies; Thrombosis; Tomography, X-Ray Computed; Vitamin K

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Topics: Algorithms; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Renal Dialysis; Secondary Prevention; Thrombosis; Venous Thromboembolism; Vitamin K; Warfarin

The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS.. Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written.. Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre.. This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.

Topics: 4-Hydroxycoumarins; Anticoagulants; Antiphospholipid Syndrome; Delphi Technique; Female; Humans; Indenes; Pregnancy; Pregnancy Complications; Thrombosis; Vitamin K

A 79-year-old man with a history of bioprosthetic aortic valve (AV) replacement in 2008 and atrial fibrillation was admitted with acute pulmonary oedema. Transthoracic and transoesophageal echocardiograms revealed significantly elevated AV gradients and thickened AV leaflets. These findings were suggestive of bioprosthetic valve thrombosis (BVT). The patient was treated with intravenous heparin and commenced on vitamin K antagonist. BVT remains an under recognised cause of late prosthetic valve dysfunction. A lack of awareness of BVT occurring beyond 3 months post-implantation is likely to account for this. Furthermore, structural valve degeneration is the most common mechanism of late prosthetic valve dysfunction. Recognising the difference between the two aetiologies is crucial as the management plan differs significantly. Here, we report a case of very late bioprosthetic AV thrombosis diagnosed 8 years after implantation. This was successfully treated with systemic anticoagulation, thereby avoiding the need for redo cardiac surgery.

Topics: Aged; Anticoagulants; Aortic Valve; Bioprosthesis; Echocardiography, Transesophageal; Heart Valve Prosthesis Implantation; Heparin; Humans; Male; Pulmonary Edema; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period.

Topics: Adult; Aged; Anticoagulants; Aortic Valve; Aspirin; Bioprosthesis; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Mexico; Middle Aged; Retrospective Studies; Risk Factors; Thrombosis; Vitamin K

Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis.. We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls.. The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times.. In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.

Topics: Aged; Anticoagulants; Female; Hemorrhage; Humans; Incidence; Italy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Retrospective Studies; Survival Analysis; Thrombosis; Treatment Outcome; Vitamin K

Atrial arrhythmias (AA) induce a high rate of thromboses and require vitamin K antagonists (VKA) or direct anticoagulants (DOAC) prescriptions. Essential thrombocythemia (ET) and polycythemia vera (PV) are also pro-thrombotic diseases. The prevention of thromboses is based on the association of cytoreductive drug and low-dose aspirin (LDA). We studied the incidence and complications of AA among patients with ET or PV. We identified 96/713 patients (13.5%) carrying AA. These patients were older (median 72.1 vs. 61.3 years old, p < 0.0001). In a case-control analysis, we observed that patients with AA had a higher frequency of cardiovascular risk factors (77/96, 80% vs. 61/96, 61%; p = 0.01). A higher incidence of thromboses before and after myeloproliferative neoplasm (MPN) diagnosis was seen in this group: 26/96, 27.1% vs. 14/96, 14.6% (p = 0.03) and 34/96, 35% vs. 18/96, 18.8% (p = 0.009). Most of the events were arterial (82 vs. 61%, p = 0.09). This translates into a shorter thrombosis-free survival (11.0 vs. 21.6 years, p = 0.01). Continuation of LDA in this situation exposed patients to more thrombotic events (p = 0.04) but VKA did not seem to be good anticoagulant drugs either. The association of AA and MPN is more frequent than expected. AA clearly increased the thrombotic risk of these patients. Anticoagulant drugs should be carefully managed between cardiologists and hematologists. Association of LDA and VKA or the role of DOAC in such population should be rapidly discussed to reduce the thrombotic rate.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Arrhythmias, Cardiac; Female; France; Humans; Incidence; Indenes; Male; Middle Aged; Myeloproliferative Disorders; Risk Factors; Thrombosis; Vitamin K

We examined the risks of all-cause mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists (VKAs) and non-VKAs oral anticoagulants (NOACs) following traumatic injury in atrial fibrillation (AF) patients.. This was a Danish nationwide registry-based study (2005-16), including 4541 oral anticoagulant (OAC)-treated AF patients experiencing traumatic injury (defined as traumatic brain injury, hip fracture, or traumatic torso or abdominal injury). Within 90 days following discharge from traumatic injury, 60.6% resumed VKA (median age = 80, CHA2DS2-VASc = 4, HAS-BLED = 2), 16.7% resumed NOAC (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 2), and 22.7% did not resume OAC treatment (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 3). Switch from VKA to NOAC occurred among 9.5%. Since 2009, the trend in OAC resumption increased (P-value <0.0001), in particular with NOACs (P-value <0.0001). Follow-up started 90 days after discharge, and time-varying multiple Cox regression analyses were used for comparisons. Compared with non-resumption, VKA and NOAC resumption were associated with lower hazard [95% confidence interval (CI)] of all-cause mortality [hazard ratio (HR) 0.48 (0.42-0.53) and HR 0.55 (0.47-0.66), respectively] and ischaemic stroke [HR 0.56 (0.43-0.72) and HR 0.54 (0.35-0.82), respectively], increased major bleeding hazard [HR 1.30 (1.03-1.64) and HR 1.15 (0.81-1.63), respectively], and similar hazard of recurrent traumatic injury [HR 0.93 (0.73-1.18) and HR 0.87 (0.60-1.27), respectively].. AF patients resuming VKA and NOAC treatment following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury. Withholding OAC following a traumatic injury in AF patients may not be warranted.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cause of Death; Female; Hemorrhage; Humans; Male; Recurrence; Registries; Retrospective Studies; Risk Factors; Stroke; Thrombosis; Vitamin K; Wounds and Injuries

Clinicians struggle daily with the optimal regimen for patients with an indication for antiplatelet therapy after stenting and in patients needing oral anticoagulation treatment for atrial fibrillation (AF). This is not only difficult in patients with acute coronary syndrome (ACS) but also in the large number of patients with AF undergoing elective percutaneous coronary intervention (PCI). The challenge is to strike a balance between the increasing risk of bleeding events and ischemic or thrombotic events. Until recently, guidelines were based on expert consensus and a few small, many of them retrospective, trials. A so-called triple therapy with a vitamin K antagonist (VKA) and dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended for patients with AF undergoing PCI in stable coronary artery disease or for those with ACS. However, severe bleeding complications remain a major issue during triple therapy, particularly in the growing aging population. In the past year, randomized controlled trials (RCT) with direct-acting oral anticoagulants (DOACs) have modified the standard use of care, now favoring dual therapy with DOACs. This review elucidates the current influential RCTs on the new antiplatelet and anticoagulation strategies for patients with AF undergoing PCI or with ACS, and discusses whether triple therapy is still required.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Guideline Adherence; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Factors; Stents; Stroke; Thrombosis; Vitamin K

Topics: Antibodies, Antiphospholipid; Anticoagulants; Humans; Recurrence; Rivaroxaban; Thrombosis; Treatment Outcome; Vitamin K

Point of care testing (POCT) must comply with regulatory requirements according to standard EN ISO 22870, which identify biologists as responsible for POCT. INR for vitamin K antagonists (VKAs) monitoring is a test frequently performed in haemostasis laboratories. Bedside INR is useful in emergency room, in particular in case of VKAs overdosage but also for specific populations of patients like paediatrics or geriatrics. INR POCT devices are widely used at home by the patients for self-testing, but their use in the hospital by the clinical staff for bedside measurement is growing, with devices which now comply with standard for POCT accreditation for hospital use. The majority of point of care devices for INR monitoring has shown a good precision and accuracy with results similar to those obtained in laboratory. With the aim to help the multidisciplinary groups for POCT supervision, the medical departments and the biologists to be in accordance with the standard, we present the guidelines of the GFHT (Groupe français d'étude sur l'hémostase et la thrombose, subcommittee "CEC et biologie délocalisée") for the certification of POCT INR. These guidelines are based on the SFBC guidelines for the certification of POCT and on the analysis of the literature to ascertain the justification of clinical need and assess the analytical performance of main analysers used in France, as well as on a survey conducted with biologists.

Topics: 4-Hydroxycoumarins; Accreditation; Adult; Aged; Anticoagulants; Certification; Child; Humans; Indenes; International Normalized Ratio; Laboratories; Monitoring, Physiologic; Point-of-Care Testing; Reference Standards; Thrombosis; Vitamin K

Antiphospholipid syndrome (APS) is a condition in which the presence of antibodies against phospholipid-binding proteins is associated with thrombophilia and/or pregnancy morbidity. Although antiphospholipid antibodies have anticoagulant characteristics in vitro, they are associated with thromboembolic complications. Thrombin generation (TG) is a sensitive global test of coagulation, and elevated TG is associated with thrombosis. Increased TG can be caused by increased prothrombin conversion, decreased thrombin inactivation, or a combination of both. In this study, we measured TG in APS patients and healthy controls with and without vitamin K antagonist (VKA) treatment at 1 and 5 pM tissue factor and with thrombomodulin. Prothrombin conversion and thrombin inactivation were determined by thrombin dynamics analysis. The TG peak was increased in nontreated APS patients at 1 pM TF compared with nontreated controls. Prothrombin conversion was significantly increased in nontreated APS patients. In contrast, prothrombin conversion did not differ in controls and patients that were on VKA therapy. Thrombin inactivation was comparable between controls and APS patients in the presence and absence of VKAs. Both TG (peak and ETP) and prothrombin conversion were significantly higher in APS patients with prior thrombosis compared with patients without a history of thrombosis. In this study, we demonstrate that in APS, the hemostatic balance shifts toward a more prothrombotic phenotype due to elevated prothrombin conversion but unchanged thrombin inactivation rates. Within the group of APS patients, increased TG and prothrombin conversion are associated with a history of thrombosis.

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Male; Middle Aged; Prothrombin; Thrombomodulin; Thrombosis; Vitamin K

This study aimed to describe patterns of long-term antithrombotic use in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) in Korea and their impacts on clinical events before introduction of non-vitamin K antagonist oral anticoagulants (NOAC) into practice in 2015.. Patients with NVAF who were admitted due to the AIS and discharged no later than 2008 were enrolled retrospectively. Data were collected at 11 time points during the first 3 years of follow-up. The primary outcome event was a composite of stroke recurrence, major bleeding, and death. Vitamin K antagonist (VKA) users were categorized into a well-controlled INR group and a poorly-controlled INR group (modified TTR ≥47.0% vs <47.0%).. Of 1,350 patients enrolled in this study, 95% were on antithrombotic medications at discharge. The rate of VKA usage decreased over time (77% and 40% at discharge and 3 years, respectively). The cumulative event rates of the primary outcome differed by treatment patterns. Among the 10 most frequent treatment types, the highest outcome rate was observed in patients who started with VKA-only therapy but discontinued VKAs during follow-up without restarting (70.2%); this was followed by those starting with antiplatelet-only therapy and stopping it without restart (66.7%). Among VKA users, the 3-year cumulative primary outcome rates were higher in the poorly-controlled INR group than the well-controlled INR group (24.5% vs 15.7%; p = 0.015).. Our study revealed that, in pre-NOAC era, there was a wide spectrum of long-term antithrombotic use. The incidence of the composite outcome also varied by patterns of antithrombotic use.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Republic of Korea; Retrospective Studies; Stroke; Thrombosis; Treatment Outcome; Vitamin K

The objective was to describe the management and risk factors for complications of antiphospholipid syndrome (APS) patients who underwent a surgical procedure in a single center. We reviewed medical records of all patients with primary or secondary APS who underwent an elective surgery during a 6-year period. Demographical data, management of anticoagulation and complications were recorded. We identified 43 patients, mean age 37.9 ± 8.9 years, who underwent a total of 48 elective surgeries. All patients had history of at least one thrombotic event and were under vitamin K antagonists. Before surgery, all patients received bridging therapy with intravenous infusion of heparin or low molecular weight heparin (LMWH). Among the LMWH group, 36 had a full anticoagulation regimen and nine prophylactic doses. In 62% of the surgeries, we identified an optimal management of periprocedural anticoagulation according to guidelines. Overall six patients had severe bleeding and three thrombotic complications (full anticoagulation regimen n = 2 and prophylactic dose group n = 1). Patients with optimal management of anticoagulation experienced less thrombotic and hemorrhagic complications (7 vs. 33%; OR 0.14, 95% CI 0.02-0.81; p = 0.040) and patients with INR ≤1.5 at surgery had fewer episodes of major bleeding (6 vs. 29%; OR 0.19, 95% CI 0.02-0.98; p = 0.050). All three thrombotic events occurred in patients with INR ≤1.5. Proper management of anticoagulation based on guidelines is associated with less complications in patients with APS. Notwithstanding the proper use of bridging therapy, some patients may develop thrombotic complications.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Chi-Square Distribution; Drug Administration Schedule; Elective Surgical Procedures; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Male; Medical Records; Mexico; Middle Aged; Odds Ratio; Perioperative Care; Retrospective Studies; Risk Factors; Surgical Procedures, Operative; Tertiary Care Centers; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

Intracardiac thrombosis is a rare complication of Behçet's disease (BD), which may manifest as intracardiac tumor. In half of cases, its detection precedes the diagnosis of MB. High mortality rates may be related to post-surgical complications and/or pulmonary arteries involvement. We report the case of a 29-year old young patient, with a previous history of bipolar aphthosis, who underwent surgery after the detection of right atrium and ventricle tumor. Anatomo-pathological examination showed thrombus and MB was diagnosed in the postoperative period. Patient's evolution was favorable under medical treatment based on corticosteroids, colchicine and vitamin K antagonists (AVK). The detection of intracardiac mass in a young subject should suggest the diagnosis of cardiac thrombus and Behçet's disease, even in the absence of ethnic or geographical risk factors.

Topics: Adrenal Cortex Hormones; Adult; Behcet Syndrome; Colchicine; Heart Diseases; Heart Neoplasms; Humans; Male; Thrombosis; Vitamin K

The need for transesophageal echocardiography (TEE) before catheter ablation of atrial fibrillation (CA-AF) is still being questioned. The aim of this study is to analyze patients' (patients) risk factors of left atrial appendage thrombus (LAAT) prior to CA-AF in daily clinical practice, according to oral anticoagulation (OAC) strategies recommended by current guidelines.. All patients scheduled for CA-AF from 01/2015 to 12/2016 in our center were included and either treated with NOACs (novel-OAC; paused 24-hours preablation) or continuous vitamin K antagonists (INR 2.0-3.0). All patients received a preprocedural TEE at the day of ablation. Two groups were defined: (1) patients without LAAT, (2) patients with LAAT. The incidence of LAAT was 0.78% (13 of 1,658 patients). No LAAT was detected in patients with a CHA. The incidence of LAAT in patients scheduled for CA-AF is low. Therefore, periprocedural OAC strategies recommended by current guidelines seem feasible. Preprocedural TEE may be dispensed in patients with a CHA

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Catheter Ablation; Cohort Studies; Echocardiography, Transesophageal; Female; Humans; Incidence; Male; Middle Aged; Precision Medicine; Predictive Value of Tests; Risk Assessment; Stroke Volume; Thrombosis; Treatment Outcome; Vitamin K

Studies on long-term utilization of non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) are scarce. We evaluated predictors of use and long-term persistence of NOACs in a real-world setting.. This population-based cohort study used the computerized databases of the Canadian Province of Quebec's health insurance. Patients with a first NVAF diagnosis from 2011 until 2014 were included. A logistic regression model yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of treatment initiation with NOACs versus VKAs. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% CIs for predictors of switching from VKAs to NOACs versus remaining on VKAs, and for predictors of discontinuation of anticoagulation treatment.. Of the 62 867 newly diagnosed NVAF patients, 14 646 initiated NOACs and 17 685 VKAs. Initiation with NOACs was less likely for patients ≥ 80 years old (OR 0.55, 95% CI 0.41-0.73) or with CHA. Older, high-risk patients are less likely to initiate NOACs than VKAs. NOAC users show a higher long-term persistence than VKA users, and older, high-risk patients are less likely to discontinue anticoagulation treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quebec; Risk Factors; Thrombosis; Vitamin K

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Arginine; Consensus; Dabigatran; Evidence-Based Medicine; Factor Xa; Forecasting; Hemorrhage; Humans; Piperazines; Recombinant Proteins; Risk Factors; Thrombosis; Vitamin K

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Consensus; Coronary Artery Disease; Drug Substitution; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Stents; Thrombosis; Vitamin K

Antiphospholipid syndrome (APS) is a common acquired thrombophilia associated with a high thrombotic risk, in which vitamin K antagonists (VKA) represent the mainstay of therapy. Case series involving up to 35 patients with APS suggested limited efficacy and safety of direct oral anticoagulants (DOACs).. In the prospective case series we followed 56 consecutive patients with APS (44 women and 12 men, aged from 22 to 64years), including 33 (60%) associated with systemic lupus erythematosus (SLE) and 16 (28.6%) with triple APS who were treated with DOACs due to their preferences or unstable anticoagulation with VKA. DOACs were started at least 3months since the thromboembolic event in patients with D-dimer below 500ng/ml.. Forty-nine (87.5%) patients were treated with rivaroxaban, 4 (7.3%) with dabigatran and 3 (5.4%) with apixaban. During follow-up of 2 to 43 (mean 22) months, 6 (10.7%, 5.8 per 100 patient-years) patients (4 women and 2 men, 4 with triple positive APS) experienced recurrent thrombosis, including deep vein thrombosis (n=4, including 2 episodes preceded by nonadherence), superficial vein thrombosis (n=1) and non-ST elevation myocardial infarction (n=1). The recurrence rate of VTE on DOACs was 5.8 per 100 patient-years. Two patients (3.6%) experienced severe bleeding.. This case-series suggests that DOACs are safe in patients with APS. These findings need to be confirmed in larger studies.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Vitamin K; Young Adult

We report a case of a patient supported with a HeartWare left ventricular assist device for idiopathic cardiomyopathy who was resistance to vitamin-K antagonists three months after implantation. The patient initially started low-molecular-weight heparin therapy and then, after the onset of an ischemic stroke, switched to dabigatran etexilate (DE). The patient had progressive recovery of cardiac function for which the device was explanted. No thrombotic or bleeding events occurred during DE therapy.

Topics: Aged; Antithrombins; Cardiomyopathy, Dilated; Dabigatran; Female; Follow-Up Studies; Heart-Assist Devices; Humans; Postoperative Care; Thrombosis; Vitamin K

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, life-threatening haematological disorder. It is characterised by complement induced haemolytic anaemia, thrombosis and impaired bone marrow function. Thrombosis most commonly occurs in the hepatic, portal, superior mesenteric and cerebral veins. A22-year female, previously diagnosed with severe aplastic anaemia treated with anti-lymphocyte globulin (ALG) and cyclosporine, had become transfusion independent for more than 10 years. She presented with abdominal pain and vomiting, initially diagnosed with portal and superior mesenteric vein thrombosis. Immunophenotyping by flow cytometry revealed a diagnosis of paroxysmal nocturnal haemoglobinuria type III. She was treated with vitmamin K anatagonist and platelet transfusion.

Topics: Adult; Female; Flow Cytometry; Hemoglobinuria, Paroxysmal; Humans; Immunophenotyping; Mesenteric Veins; Platelet Transfusion; Thrombosis; Treatment Outcome; Vitamin K; Vitamins

This study aimed to describe the real-life incidence of bleeding, arterial thrombotic events and death during vitamin K antagonist (VKA) treatment in atrial fibrillation (AF).. This was a cohort study in Echantillon Généraliste de Bénéficiaires, the 1/97 sample of the French national healthcare claims and hospitalization database, of new VKA users with definite or probable AF and no other indication, and of patients without AF, from 2007 to 2011. Prespecified outcomes were all-cause death, hospitalization for bleeding, arterial thrombotic event (ATE), or acute coronary syndrome (ACS) or any of the above (composite outcome).. Of 8894 new VKA users, 3345 had probable or certain AF, 51.7% were male, mean age was 75.1 years, 87.1% had a CHA2 DS2 -VASc score ≥ 2 and 11.6% a HAS-BLED score > 3. Among AF patients, during VKA exposure the incidence rate of bleeding was 2.8 [95% confidence interval (CI) 2.2, 3.4] per 100 patient-years, including 0.6 (95% CI 0.3, 0.8) cerebral, 1.0 (95% CI 0.7, 1.3) digestive and 1.4 (95% CI 1.0, 1.7) other bleeds. There were 1.6 (95% CI 1.2, 2.0) ACS, 1.5 (95% CI 1.1, 1.8) ATE and 3.8 (95% CI 3.2, 4.4) deaths per 100 patient-years. The incidence rate of the composite outcome was 9.1 per 100 patient-years (95% CI 8.2, 10.0). When patients stopped VKA, bleeding decreased (RR 0.67, 95% CI 0.43, 1.04)), but death or thrombosis increased (RR 3.06, 95% CI 2.46, 3.81 and 1.75, 95% CI 1.14, 2.70, respectively). During VKA exposure non-AF patients had similar rates of bleeding, but fewer deaths, ACS and ischaemic events.. Real-life rates for bleeding, arterial thrombotic events, ACS and deaths in AF patients treated with VKA were similar to those observed in clinical trials.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Atrial Fibrillation; Databases, Factual; Female; France; Hemorrhage; Hospitalization; Humans; Incidence; Male; Middle Aged; Thrombosis; Vitamin K

The prevalence of medical conditions representing a risk for thromboembolic complications and requiring antithrombotic therapy increases gradually with age. Two cases of fatal noncritical organ bleeding complication that occurred during the conversion period from initial fondaparinux to vitamin K antagonist are presented. An 81-year-old obese female patient (body mass index 43 kg/m(2)) with previous postoperative thrombosis underwent uneventful total knee replacement under spinal anesthesia. She presented with popliteal hematoma during conversion to oral anticoagulant. A 92-year-old female patient (body mass index 33 kg/m(2)) with left lower limb thrombosis was referred to our orthopedics department from her senior citizens' home for right lower limb hematoma and ischemia that occurred during conversion to oral anticoagulant. Thromboembolic and bleeding events in the elderly are real public health problems. Specific guidelines dedicated to this particular population are needed, which will improve the management of anticoagulation and decrease risk of complications.

Topics: Age Factors; Aged, 80 and over; Anticoagulants; Fatal Outcome; Female; Fondaparinux; Hemorrhage; Humans; Obesity; Polysaccharides; Risk Factors; Thromboembolism; Thrombosis; Vitamin K

Antiphospholipid Syndrome (APS) is often complicated by ischemic vascular events. Vitamin K Antagonists (VKAs) reduce the risk of recurrent thrombosis. Quality of VKAs treatment, as assessed by the Time in Therapeutic Range (TTR), has never been investigated in APS patients.. We performed a prospective observational study including 30 APS and 30 Atrial Fibrillation (AF) patients balanced by age and gender. All patients were treated with VKAs (INR target 2.5), and TTR was calculated.. Median TTR of APS was 53.5% vs. 68% of AF patients (p = 0.001). A multivariable linear regression analysis confirmed that the presence of APS (vs. AF) was independently associated with a worse TTR (B: -14.067, 95% Confidence Interval -25.868/-2.266, p = 0.020). The weekly dosage of VKAs was significantly higher in APS than AF patients.. APS patients disclose a lower quality of anticoagulation compared to those with AF, requiring higher doses of VKAs. The efficacy of non-vitamin K oral anticoagulants in this high-risk patients should be tested.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Quality of Health Care; Recurrence; Thrombosis; Treatment Outcome; Vitamin K

Topics: Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Dyspnea; Echocardiography; Humans; Male; Radiography; Thrombosis; Tomography Scanners, X-Ray Computed; Treatment Failure; Vitamin K

The SAMe-TT2R2 score has recently been proposed to predict the quality of vitamin K antagonist (VKA) anticoagulation control in patients with atrial fibrillation. We aimed at investigating whether the score is effective also in patients with venous thromboembolism (VTE). Patients included in the START-Register because started VKA therapy for a recent VTE episode and with > 3 months follow-up were analyzed. The score was calculated using the baseline patient's characteristics present in the electronic database of the registry, where all INR results were also available and analysed to calculate the time in therapeutic range (TTR). A total of 1308 patients (53.4 % female, median age 68 years) were analysed. During 998 patient-years follow-up, the median TTR was 63 %. The maximum score in the patients was 4, with 70 % of them having 0-1. INR controls within range (2.0-3.0) were significantly less prevalent in patients with score ≥ 2 vs 0-1 score (58.5 ± 20 % vs 61.5 ± 19 %, respectively, p = 0.046). Patients with score ≥ 2 vs 0-1 had a highly significant lower TTR during the first 3 months of therapy (53 ± 26 % and 61 ± 26 %, respectively; p=0.0001), difference mainly due to more time spent below 2.0 INR (38 ± 28 % vs 31.3 ± 26.7 %, respectively; p=0.0001). In conclusion, the study proved, for the first time, that the SAMe-TT2R2 score is useful to predict among VTE patients those who will have good (score 0-1) or less good (score ≥ 2) VKA anticoagulation control. The score can help decision-making in everyday clinical practice, especially when choosing between VKA and non-vitamin K antagonists direct anticoagulants.

Topics: Aged; Anticoagulants; Blood Coagulation; Cohort Studies; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Risk Factors; Thrombosis; Time Factors; Venous Thromboembolism; Vitamin K; Warfarin

Gastroschisis is the most common abdominal wall defect. It is characterized by herniation of the intestine and other abdominal organs through a defect in the abdominal wall. Neuroblastoma is the most common malignant tumor observed during the neonatal period. It is a neuroendocrine tumor derived from neural crest cells that develops into the adrenal gland.. We report on the undescribed association between gastrochisis and congenital neuroblastoma, diagnosised during the prenatal period. The mother was a 20-year-old healthy pregnant woman in her second pregnancy. Obstetric ultrasound examination showed a fetus presenting an abdominal wall defect on the right side of the umbilical cord, compatible with gastroschisis, and a hyperechogenic and spherical solid lesion on the left adrenal gland. Fetal magnetic resonance imaging disclosed similar features associated to a heterogeneous aspect of the liver. The diagnosis of metastatic neuroblastoma was confirmed after birth through liver biopsy. At 2 days of life, the prothrombrin time was abnormal, and the patient needed vitamin K.. We cannot rule out the possibility that a clotting defect, commonly observed in disseminated malignancies such as a metastatic neuroblastoma may be associated with the etiology of the gastroschisis, as this defect may result from a thrombosis occurring around 3 to 4 weeks of gestation, a period when neuroblasts development occurs into the adrenal medulla. However, we cannot exclude the possibility that both events may have occurred simultaneously by chance.

Topics: Abdominal Wall; Adrenal Gland Neoplasms; Adrenalectomy; Antifibrinolytic Agents; Female; Fetus; Gastroschisis; Gestational Age; Humans; Infant, Newborn; Liver Neoplasms; Neuroblastoma; Pregnancy; Thrombosis; Ultrasonography, Prenatal; Vitamin K; Young Adult

Topics: Aged; Angiogenesis Inhibitors; Anticoagulants; Aspirin; Female; Heparin, Low-Molecular-Weight; Humans; Lenalidomide; Male; Multiple Myeloma; Risk Factors; Thalidomide; Thrombosis; Vitamin K

Topics: Anticoagulants; Fibrinolytic Agents; Heparin; Humans; Thrombocytopenia; Thrombosis; Vitamin K; Warfarin

Topics: Aged; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Echocardiography; Female; Heart Valve Prosthesis Implantation; Heparin; Humans; Infusions, Intravenous; International Normalized Ratio; Mitral Valve; Mitral Valve Stenosis; Rheumatic Heart Disease; Thrombosis; Vitamin K; Warfarin

Topics: Aged; Aspirin; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Clopidogrel; Combined Modality Therapy; Coronary Angiography; Echocardiography, Transesophageal; Factor Xa Inhibitors; Humans; Male; Platelet Aggregation Inhibitors; Rivaroxaban; Septal Occluder Device; Thrombosis; Ticlopidine; Vitamin K

In patients with atrial fibrillation, oral anticoagulation with oral thrombin inhibitors (OTIs), in contrast to vitamin K antagonists (VKAs), associates with a modest increase in acute coronary syndromes (ACSs). Whether this observation is causatively linked to OTI treatment and, if so, whether OTI action is the result of a lower antithrombotic efficacy of OTI compared to VKA or reflects a yet undefined prothrombotic activity of OTI remain unclear. We analyzed platelet function in patients receiving OTI or dose-adapted VKA under static and flow conditions. In vivo, we studied arterial thrombosis in OTI-, VKA-, and vehicle-treated mice using carotid ligation and wire injury models. Further, we examined thrombus formation on human atherosclerotic plaque homogenates under arterial shear to address the relevance to human pathology. Under static conditions, aggregation in the presence of ristocetin was increased in OTI-treated blood, whereas platelet reactivity and aggregation to other agonists were only marginally affected. Under flow conditions, firm platelet adhesion and thrombus formation on von Willebrand factor, collagen, and human atherosclerotic plaque were increased in the presence of OTI in comparison to VKA. OTI treatment was associated with increased thrombus formation in injured carotid arteries of mice. Inhibition or ablation of GPIbα-thrombin interactions abolished the effect of OTI on thrombus formation, suggesting a mechanistic role of the platelet receptor GPIbα and its thrombin-binding site. The effect of OTI was also abrogated in the presence of aspirin. In summary, OTI treatment has prothrombotic activity that might contribute to the increase in ACS observed clinically in patients.

Topics: Acute Coronary Syndrome; Administration, Oral; Animals; Anticoagulants; Arteries; Aspirin; Atherosclerosis; Binding Sites; Blood Platelets; Fibrinolytic Agents; Humans; Mice; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Thrombin; Thrombosis; Vitamin K

Vitamin K antagonists (VKAs) are highly effective but have a narrow therapeutic index and require routine monitoring of the INR. The primary aim of pharmacogenetics (PGx) is to optimize patient care, achieving drug treatments that are personalized according to the genetic profile of each patient. The best-characterized genes involved in VKA PGx involve pharmacokinetics (VKORC1) and pharmacodynamics (CYP2C9) of VKA metabolism. The role of these genes in clinical outcomes (bleeding and thrombosis) during oral anticoagulant (OAC) therapy is controversial. The aim of the present study was to evaluate any potential association between genotype VKORC1 and CYP2C9 and adverse events (hemorrhagic and/or thrombotic), during initiation and long-term VKA treatment, in Caucasian patients. Furthermore, we aimed to determine if the concomitant prescription of other selected drugs affected the association between genotype and adverse events.We performed a retrospective, matched case-control study to determine associations between multiple gene variants, drug intake, and any major adverse effects in anticoagulated patients, monitored in 2 Italian anticoagulation clinics.Our results show that anticoagulated patients have a high risk of adverse events if they are carriers of 1 or more genetic polymorphisms in the VKORC1 (rs9923231) and CYP2C9 (rs1799853 and rs1057910) genes.Information on CYP2C9 and VKORC1 variants may be useful to identify individualized oral anticoagulant treatment for each patient, improve management and quality of VKA anticoagulation control, and monitor drug surveillance in pharmacovigilance programs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Cytochrome P-450 CYP2C9; Female; Genotype; Hemorrhage; Humans; Male; Polymorphism, Single Nucleotide; Retrospective Studies; Thrombosis; Time Factors; Vitamin K; Vitamin K Epoxide Reductases; White People

Bioprosthetic valve thrombosis (BPVT) is a rare but potentially life-threatening complication. Current guidelines favour surgery or thrombolysis as initial treatment. We set forth to characterize timing, diagnostic criteria and treatment strategies in BPVT.. A free-text search tool was used to identify patients diagnosed with BPVT at Mayo Clinic between 1997 and 2013. We compared patients treated initially with vitamin K antagonists (VKA group; N = 15) versus surgery/thrombolysis (non-VKA group; N = 17).. Peak incidence of BPVT was 13-24 months after implantation in both groups. VKA and surgery/thrombolysis decreased prosthetic mean gradients to a similar extent (VKA group: 13 ± 5 to 6 ± 2 mmHg in mitral position, 9 ± 3 to 5 ± 1 mmHg in tricuspid position and 39 ± 3 to 24 ± 7 mmHg in aortic/pulmonary position; non-VKA group: 16 ± 12 to 5 ± 1 mmHg in mitral, 10 ± 5 to 4 ± 1 mmHg in tricuspid and 57 ± 9 to 18 ± 6 mmHg in aortic position; P = 0.59 for group effect). NYHA class improved in 11 of 15 patients in the VKA group and 10 of 17 patients in the non-VKA group (P = 0.39). There were no deaths, strokes or recognized embolic events; 1 patient in each group experienced gastrointestinal bleeding requiring transfusion. Index transthoracic echocardiogram formally identified BPVT in a minority of patients.. BPVT may occur late after surgical implantation. VKA therapy resulted in haemodynamic and clinical improvement with minimal risk, and should be considered the first-line therapy in haemodynamically stable patients. Echocardiographic criteria for improving BPVT diagnosis are proposed.

Topics: Adult; Aged; Anticoagulants; Bioprosthesis; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Retrospective Studies; Thrombosis; Vitamin K

Atrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Fibrin; Fibrin Clot Lysis Time; Humans; International Normalized Ratio; Microscopy, Electron, Scanning; Poland; Porosity; Protein Conformation; Sweden; Thrombin; Thrombosis; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Dose-Response Relationship, Drug; Echocardiography, Transesophageal; Electric Countershock; Female; Humans; Pyrazoles; Pyridones; Recurrence; Risk Factors; Thrombosis; Treatment Outcome; Vitamin K

Direct oral anticoagulants (DOACs) are effective for stroke prevention in nonvalvular atrial fibrillation (AF). Cardioversion (CV) is frequently performed in patients with AF or flutter. To further explore the safety profile of DOACs in the context of CV, we sought to assess the prevalence of intracardiac thrombi under DOAC therapy in comparison with treatment with vitamin K antagonists. A total of 672 transesophageal echocardiograms performed in 643 patients with a history of nonvalvular AF were analyzed. The median CHA2DS2-VASc score was 4. Cases were stratified according to anticoagulation with dabigatran (n = 79), rivaroxaban (n = 122), phenprocoumon (n = 180), or bridging therapy (n = 287). In a subgroup analysis, only patients receiving phenprocoumon with an international normalized ratio ≥2 on the day of the investigation or on DOAC therapy for ≥3 weeks were considered. The prevalence of intracardiac thrombi under phenprocoumon was significantly higher than under DOACs (phenprocoumon, 17.8%; all DOACs, 3.9%; dabigatran, 3.8%; rivaroxaban, 4.1%) and showed no significant difference to bridging therapy (12.5%). In patients with sufficient short-term anticoagulation, similar differences between DOAC and phenprocoumon groups were observed (phenprocoumon, 18.4%; all DOACs, 3.8%; dabigatran, 0%; rivaroxaban, 6.6%). The influence of anticoagulation medication on thrombus rates was confirmed after adjusting for baseline intergroup differences regarding left atrial size and CHA2DS2-VASc score. In conclusion, the prevalence of intracardiac thrombi was lower under DOAC therapy than under phenprocoumon in this high-risk patient cohort. Safety of CV during DOAC treatment requires further prospective evaluation.

Topics: Aged; Anticoagulants; Arrhythmias, Cardiac; Benzimidazoles; beta-Alanine; Cohort Studies; Dabigatran; Electric Countershock; Female; Humans; Male; Middle Aged; Morpholines; Phenprocoumon; Prevalence; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K

It is unclear whether anticoagulation guidelines intended for the general population are applicable to patients with polycythemia vera (PV) and essential thrombocythemia (ET). In the present study, the risk of thrombotic recurrence was analyzed in 150 patients with PV and ET treated with vitamin K antagonists (VKA) because of an arterial or venous thrombosis. After an observation period of 963 patient-years, the incidence of re-thrombosis was 4.5 and 12 per 100 patient-years under VKA therapy and after stopping it, respectively (P < 0.0005). After a multivariate adjustment for other prognostic factors, VKA treatment was associated with a 2.8-fold reduction in the risk of thrombotic recurrence. Notably, VKA therapy offset the increased risk of re-thrombosis associated with a prior history of remote thrombosis. Both the protective effect of VKA therapy and the predisposing factors for recurrence were independent of the anatomical site involved in the index thrombosis. Treatment periods with VKA did not result in a higher incidence of major bleeding as compared with those without VKA. These findings support the use of long-term anticoagulation for the secondary prevention of thrombosis in patients with PV and ET, particularly in those with history of remote thrombosis.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Follow-Up Studies; Humans; Male; Middle Aged; Polycythemia Vera; Recurrence; Thrombocythemia, Essential; Thrombosis; Vitamin K

Anticoagulation reversal is a time-sensitive intervention for the prevention of life-threatening hemorrhagic events occurring with bleeding or surgery. Recommendations for the most effective and well tolerated reversal agent in these settings remain controversial. Several clinical guidelines for the management of intracerebral hemorrhage support use of prothrombin complex concentrates (PCCs) for the rapid reversal of warfarin-associated coagulopathy despite limited clinical data. The purpose of this investigation was to evaluate the efficacy and safety of PCC for the rapid reversal of anticoagulation by vitamin K antagonists for life-threatening bleeding or emergent surgery and to assess adherence to a hospital-based protocol. A retrospective chart review was conducted of adult patients receiving PCC for the reversal of anticoagulation. Patients were assessed according to indication for anticoagulation reversal. The primary outcome measure was adequacy of international normalized ratio reversal. Other outcomes included cessation of bleeding, thrombotic complications, and adherence to an institutional-based guideline for the use of PCC. ICU and hospital length of stay and 30-day mortality was assessed. There were 70 patients included in this study. Mean international normalized ratio was reduced from 3.1 to 1.6 following administration of at least one dose of PCC. Cessation of bleeding occurred in 65.7% of patients. Clinical assessment was unclear in 18.6%. Thrombotic complications were observed in 7.1% of patients. The 30-day mortality rate was found to be 14.3%. These data demonstrate that PCC is a well tolerated and effective method for anticoagulation reversal associated with a relatively high 30-day survival rate.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Thrombosis; Vitamin K; Young Adult

Guidelines describing the perioperative management of antithrombotic therapy in patients requiring temporary interruption of vitamin K antagonists (VKAs) were first published in 2008. The objective of this study is to evaluate the perioperative management of anticoagulation of patients on chronic VKA and the incidence of bleeding and thrombotic complications pre and postpublication of the 2008 American College of Chest Physicians (ACCP) guidelines. A retrospective review of 40 patients on chronic VKA requiring temporary discontinuation of VKA due to an invasive or surgical procedure who were referred to a single haematology practice from January 2006 to June 2010. Demographics, indications of VKA, risk factors for thrombosis, type of procedure, bridging regimen and bleeding complications were recorded pre and post-2008 ACCP guidelines. Sixty-one procedures were performed in 40 patients; 60% were women. Indications for anticoagulation were secondary prevention of venous thrombosis (n = 27), arterial thrombosis (n = 8) or both arterial thrombosis and venous thrombosis (n = 4), and primary prevention of arterial thrombosis (n = 1). Twenty patients (50%) had thrombophilia. The most common surgical and invasive procedures were gastrointestinal (33%), gynaecological (15%) and orthopaedic (11%). Bridging regimen with therapeutic-dose subcutaneous low molecular heparin (LMWH) was used in 27 (67.5%) patients, prophylactic-dose LMWH in 12 (30%) and a combination of LMWH therapeutic and prophylactic-dose doses in 11 (27.5%). Three bleeding complications occurred prepublication of the 2008 ACCP practice guidelines, although no bleeding complications occurred after the guidelines were published. Adherence to the 2008 ACCP guidelines for the perioperative management of anticoagulation reduced bleeding complications in patients on chronic VKA treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Patient Compliance; Perioperative Care; Practice Guidelines as Topic; Retrospective Studies; Risk Factors; Thrombophilia; Thrombosis; Venous Thrombosis; Vitamin K; Young Adult

The use of oral anticoagulant therapy (OAT) has constantly increased in the prevention of thromboembolism, particularly in patients 80 years of age or older.. The aim of this multicentre study was to evaluate the efficacy and safety of vitamin K antagonists (VKAs) in elderly patients managed with a computer dosing algorithm compared with a dosage decided by expert physicians.. Nine Italian thrombosis centres utilising the Zeus dosing algorithm were involved. The before-after study enrolled patients managed firstly by medical staff (manual system) or with the PARMA algorithm for 12 months from July 2008 to June 2009 and then with the Zeus algorithm during the analogous period from 2010 to 2011. Of 7605 patients in the OAT maintenance phase, 2281 were older than 80 years (mean age 84.2 years). Data for these 2281 patients managed with both modalities were analysed.. Of the 2281 patients 80 years of age or older, 1776 underwent OAT for atrial fibrillation (AF). Use of a dosing algorithm increased the OAT quality: time in therapeutic range (TTR) was significantly (p < 0.001) higher during the Zeus period than during the manual period (71.6 vs. 68.8 %). The TTR achieved with Zeus was similar to that obtained with the PARMA algorithm. In addition, patients managed with Zeus took a weekly drug dosage significantly (p < 0.01) lower than that both suggested by PARMA and prescribed by expert physicians, with a reduced number of adverse events.. This study confirms that the effectiveness and safety of VKA therapy in patients 80 years of age or older increases with computer dosing algorithms.

Topics: Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Female; Humans; Male; Retrospective Studies; Thromboembolism; Thrombosis; Vitamin K

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Electrocardiography; Factor Xa Inhibitors; Female; Humans; Phenindione; Rivaroxaban; Thrombosis; Vitamin K

Optimal dosing of prothrombin complex concentrate (PCC) has yet to be defined and varies widely due to concerns of efficacy and thrombosis. We hypothesized a dose of 15 IU/kg actual body weight of a three-factor PCC would effectively correct coagulopathy in acute care surgery patients. Retrospective review of 41 acute care surgery patients who received 15 IU/kg (± 10%) actual body weight PCC for correction of coagulopathy. Demographics, laboratory results, PCC dose, blood and plasma transfusions, and thrombotic complications were analyzed. We performed subset analyses of trauma patients and those taking warfarin. Mean age was 69 years (18-94 years). Thirty (73%) trauma patients, 8 (20%) emergency surgery patients, 2 (5%) burns, and 1 (2%) nontrauma neurosurgical patient were included. Mean PCC dose was 1305.4 IU (14.2 IU/kg actual body weight). Mean change in INR was 2.52 to 1.42 (p 0.00004). Successful correction (INR <1.5) was seen in 78 per cent. Treatment failures had a higher initial INR (4.3 vs 2.03, p 0.01). Mean plasma transfusion was 1.46 units. Mean blood transfusion was 1.61 units. Patients taking prehospital warfarin (n = 29, 71%) had higher initial INR (2.78 vs 1.92, p 0.05) and received more units of plasma (1.93 vs 0.33, p 0.01) than those not taking warfarin. No statistical differences were seen between trauma and nontrauma patients. One thrombotic event occurred. Administration of low-dose PCC, 15 IU/kg actual body weight, effectively corrects coagulopathy in acute care surgery patients regardless of warfarin use, diagnosis or plasma transfusion.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Body Weight; Burns; Drug Dosage Calculations; Emergencies; Humans; International Normalized Ratio; Middle Aged; Plasma; Retrospective Studies; Surgical Procedures, Operative; Thrombosis; Vitamin K; Warfarin; Wounds and Injuries; Young Adult

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Drug Monitoring; Hemorrhage; Humans; International Normalized Ratio; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Administration, Oral; Aged; Anticoagulants; Blood Coagulation; Female; Humans; Male; Prothrombin Time; Thrombosis; Vitamin K

The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26 (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86-1.49). Short-term use (< 1 month) of vitamin K-antagonists (VKA) yielded an aOR of 1.85 (95 %CI 0.97-3.51) which dropped after 3+ years to 1.24, 95 %CI: 0.86-1.77. The risk of SAH was higher in subjects in dual antithrombotic treatment (aOR 2.08, 95 %CI: 1.26-3.44), and in triple antithrombotic treatment (aOR 5.74, 95 %CI: 1.76-18.77). In conclusion, use of aspirin,clopidogrel and VKA were only associated with an increased risk of SAH in the first three months after starting treatment. Long-term aspirin use carried no reduced SAH risk. Results should be interpreted cautiously due to their observational nature.

Topics: Aged; Aspirin; Case-Control Studies; Clopidogrel; Denmark; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Risk; Subarachnoid Hemorrhage; Thrombosis; Ticlopidine; Vitamin K

Vitamin K antagonists are commonly used for the prevention of thromboembolic events. Patient self-monitoring of vitamin K antagonists has proved superior to usual care. Dabigatran has been shown, relative to warfarin, to reduce thromboembolic events without increasing bleeding.. We constructed a Markov model to compare vitamin K self-monitoring strategies to dabigatran including effectiveness and costs of monitoring and complications (thromboembolism and major bleeding). The model was used to project the incidence of these complications, life years, quality-adjusted life years, and health system costs with anticoagulant treatment throughout life. The analysis was conducted from the health system perspective and from the societal perspective.. Low quality evidence suggests that self-monitoring is at least as effective as dabigatran for the outcomes of thrombosis, bleeding and death. Moderate quality evidence that patient self-monitoring is more effective than other forms of monitoring degree of anticoagulation with vitamin K antagonists, reducing the relative risk of thromboembolism by 41% and death by 34%. The cost per quality adjusted year gained relative to other warfarin monitoring strategies is well below 30,000 € in the short term, and is a dominant alternative from the fourth year. In comparison with dabigatran, the lower annual cost and its equivalence in terms of effectiveness made self-monitoring the dominant option. These results were confirmed in the probabilistic sensitivity analysis.. We have moderate quality evidence that self-monitoring of vitamin K antagonists is a cost-effective alternative compared with hospital and primary care monitoring, and low quality evidence, compared with dabigatran. Our analyses contrast with the available cost analysis of dabigatran and usual care of anticoagulated patients.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Monitoring; Fibrinolytic Agents; Hemorrhage; Humans; Male; Markov Chains; Quality-Adjusted Life Years; Self Care; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Drug Substitution; Factor Xa Inhibitors; Humans; Thrombosis; Vitamin K

Thrombin generation assay (TGA) is useful as a global functional test for assessing bleeding or thrombotic risk and its modification with therapy. We investigated TGA to assess anticoagulation status compared with the international normalized ratio (INR) system in patients with primary thrombophilia receiving and not undergoing thromboprophylaxis.. We studied 50 patients with at least one thrombotic event and a confirmed diagnosis of inherited thrombophilia. Thrombin generation was measured in platelet-poor plasma by calibrated automated thrombography (CAT).. Patients in optimal anticoagulation (INR: 2.0-3.0) showed an endogenous thrombin potential (ETP) of 14-56% of normal and a peak of 18-55% of normal. A significant inverse relationship between INR and thrombin generation parameters (ETP, peak and velocity index) and a linear correlation for lag time was found in patients treated with vitamin-K antagonists (VKA). Receiver-operating characteristics (ROC) analysis showed that the optimal cutoff for ETP was 1600.2 nM · min (111.6% of normal, with a sensitivity of 96.6% and a specificity of 92.9%) and for the peak was 298.3 nM (112.1% of normal, with a sensitivity of 96.4% and a specificity of 100%). According to this analysis, ETP was able to identify patients with increased thrombotic and hemorrhagic risk, correlating with severe clinical complications.. TGA showed excellent sensitivity and specificity for assessing anticoagulation status in patients with primary thrombophilia receiving VKA, with significant advantages with regard to INR. Clinical data strongly support ETP as a valuable indicator of thrombotic or hemorrhagic risk in patients receiving or not receiving thromboprophylaxis.

Topics: Adult; Anticoagulants; Calibration; Cohort Studies; Female; Healthy Volunteers; Hemorrhage; Heterozygote; Humans; International Normalized Ratio; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Risk Factors; ROC Curve; Thrombelastography; Thrombin; Thrombophilia; Thrombosis; Vitamin K; Young Adult

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Consensus; Humans; Terminology as Topic; Thrombosis; Vitamin K

To identify, in a case-control study, the risk factors associated with a thrombotic or bleeding event in patients treated with vitamin K antagonists.. We performed a single-centre observational study during a three-month period where we consecutively included patients admitted to the emergency department of a secondary-level hospital and treated with vitamin K antagonists, regardless the reason for admission. Patients admitted for a thrombotic or bleeding event were included as cases and the other patients served as controls. Main thrombotic or bleeding risk factors during vitamin K antagonist therapy were a priori identified in literature and tested in conditional logistic regression.. Two hundred and forty subjects were identified, 40 of which (17%) were admitted for a bleeding event, 19 (8%) for a thrombotic event and 181 (75%) for another reason. Over 85% of patients were treated with fluindione. No risk factor was significantly associated with bleeding or thrombotic event in patients treated with vitamin K antagonist. Patients presenting a thrombotic event were however more likely to have a chronic respiratory disease.. In this study, no risk factor significantly associated with a bleeding or thrombotic event in patients treated with vitamin K antagonist were identified. The occurrence of these events supposes other risk factors, including potential genetic polymorphisms that should be considered in future studies.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Drug Interactions; Emergency Service, Hospital; Female; Genetic Predisposition to Disease; Hemorrhage; Humans; International Normalized Ratio; Male; Phenindione; Respiration Disorders; Risk Factors; Secondary Care Centers; Thrombosis; Vitamin K; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Global Health; Hemorrhage; Humans; Incidence; Male; Risk Assessment; Thrombosis; Vitamin K

A main goal in clinical management of patients with antiphospholipid syndrome (APS) is to prevent thrombotic recurrences and/or miscarriages. For many decades, the only available oral anticoagulant drugs have been vitamin K antagonists (VKA), which are still the cornerstone of long-term treatment of thromboembolism. However, the limits of VKA treatment are well known: narrow therapeutic window and high patient-to-patient variability of response. Moreover, in some patients with APS a higher international normalized ratio (INR) therapeutic target was suggested, and INR inaccuracy due to antiphospholipid antibodies was reported. Therefore, VKA management in APS patients is frequently cumbersome, requires close INR monitoring and may affect patient's quality of life. A new class of oral anticoagulant agents has been developed, the Direct Oral Anticoagulants (DOA), which directly inhibit a single enzyme of the coagulation cascade. Compared with VKA, they have more stable pharmacokinetic and pharmacodynamic profiles, little interaction with food or drugs with a predictable anticoagulation effect, they can thus be prescribed in a fixed dose, without requiring frequent laboratory monitoring. The efficacy and safety of DOA has been shown in large phase III clinical trials. Unfortunately, translating these good results to APS patients is not straightforward: currently, at least three randomized controlled clinical trials are ongoing.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Pregnancy; Thrombosis; Vitamin K

Outcome of sirolimus-eluting stent (SES) in patients treated with an antivitamin K (VKA) agent before the PCI procedure is unknown.. A total of 7651 patients were selected among 15,147 recipients of SES, included in the worldwide e-SELECT registry, only from those centers which included at least one patient requiring VKA: 296 were pretreated with a VKA agent (VKA group), whereas 7355 patients from the same enrolling medical centers were not (NON-VKA group). The rates of 1) major adverse cardiac events (MACE), including all-cause deaths, myocardial infarction (MI) and target lesion revascularization, 2) stent thrombosis (ST) and 3) major bleeding (MB) in the 2 study groups were compared at 1, 6 and 12 months.. The patients in VKA group were on average older as compared to those in NON-VKA group (67.7 ± 9.9 vs.62.9 ± 10.7, P<0.001). The indications for pre-procedural anticoagulation were atrial fibrillation in 177 (59.8%), presence of a prosthetic valve in 21 (7.1%), embolization of cardiac origin in 17 (5.7%), pulmonary embolism or deep vein thrombosis in 17 (5.7%), and miscellaneous diagnoses in 64 (21.6%) patients. At 1 year, the rates of MACE and MB were higher in the VKA vs. the NON-VKA group (8.3% and 3% vs. 5.3% and 1.2%, P<0.04 and P<0.002, respectively). The 1-year rates of definite and probable ST were remarkably low in both groups (0.38% vs. 1.1%, p=0.4).. Selected patients anticoagulated with VKA agent may safely undergo SES implantation. Those patients may receive a variety of APT regimen at the cost of a moderate increased risk of MB.

Topics: Aged; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prosthesis Implantation; Registries; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

Topics: Acute Disease; Adult; Anticoagulants; Antiviral Agents; Blood Coagulation; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Male; Risk Factors; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Humans; International Normalized Ratio; Stroke; Thrombosis; Vitamin K

Recurrent bleeding can complicate the treatment of thrombosis patients with vitamin K antagonists (VKA), even at a well-regulated level of anticoagulation. In this proof-of-principle study, we investigated whether alterations in platelet function or von Willebrand factor (vWf) contribute to a bleeding phenotype in these patients.. In this case-control study 33 well-regulated patients without bleeding events (controls) and 33 patients with recurrent bleeding (cases) were retrospectively included. Thrombin generation and vWf were determined in plasma. Platelet function was assessed by light transmission aggregometry and flow cytometry using a validated panel of agonists.. Thrombin generation was similarly reduced in controls and cases, in comparison to normal plasma. Plasma vWf level was above the normal range in 85% of controls and 67% of the cases. vWf activity was similarly increased in all patients in comparison to healthy volunteers. Platelet aggregation was in the normal range for almost all patients irrespective of the type of agonist. However, in response to a low collagen dose, platelets from 21% of controls and 27% of cases showed diminished responses. Agonist-induced secretion of alpha- and dense-granules or integrin αIIbβ3 activation were affected in platelets from neither controls nor cases.. Recurrent bleeding in well-controlled patients on VKA therapy is not explained by anti-hemostatic changes in platelet or vWf function.

Topics: Aged; Blood Platelet Disorders; Blood Platelets; Case-Control Studies; Female; Hemorrhage; Humans; Integrins; Male; Platelet Aggregation; Recurrence; Thrombin; Thrombosis; Vitamin K; von Willebrand Factor

Bleeding risk (often perceived, rather than actual) is a common reason for cessation of oral anticoagulation with Vitamin K antagonists (VKA). We investigate clinical outcomes in a consecutive population of VKA naïve atrial fibrillation (AF) patients, who initiated VKA therapy in our clinic. We included consecutive VKA-naïve patients with non valvular AF, initiated on VKA therapy in our anticoagulation outpatient clinic in 2009. During follow-up, adverse events [thrombotic/vascular events (stroke, acute coronary syndrome, acute heart failure and cardiac death), major bleeding and death], and VKA cessation were recorded. At the end of the follow-up, we determined time within therapeutic range (TTR), using a linear approximation (Rosendaal method). We studied 529 patients (49% male, median age 76), median follow-up 835 days (IQR 719-954). During this period 114 patients stopped VKA treatment. 63 patients suffered a thrombotic/cardiovascular event (5.17%/year, 27 thrombotic/ischaemic strokes), 51 major bleeding (4.19%/year) and 48 died (3.94%/year). Median TTR was 54% (34-57). On multivariate analysis (adjusted by CHA₂DS₂-VASc score), VKA cessation was associated with death [Hazard Ratio (HR) 3.43; p<0.001], stroke [4.21; p=0.001] and thrombotic/cardiovascular events [2.72; p<0.001]. Independent risk factors for major bleeding were age [1.08; p<0.001], previous stroke [1.85; p=0.049], and TTR [0.97; p=0.001], but not VKA cessation. In conclusion, in AF patients AF, VKA cessation is independently associated with mortality stroke and cardiovascular events. Specifically, VKA cessation independently increased the risk of stroke, even after adjusting for CHA₂DS₂-VASc score. TTR was an independent risk factor for major bleeding following initiation of VKA therapy.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Humans; Male; Risk; Survival Analysis; Thrombosis; Vitamin K; Withholding Treatment

Topics: Aged; Anticoagulants; Atrial Appendage; Factor Xa Inhibitors; Female; Heart Diseases; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Tomography, X-Ray Computed; Vitamin K

The indications for antithrombotic treatment with vitamin K antagonists are now relatively precise, but management of this treatment is often difficult in clinical practice and be set by problems such as unstable hypocoagulability, an increased bleeding risk, interactions with other therapies and pathologies, and high-level vitamin K intake in the diet. Rigorous and accurate information of the patient and family, along with regular and frequent control of the international normalized ratio (INR), are essential for the safety and efficacy of this treatment. Some physicians cite an excessive bleeding risk as one reason for withholding oral anticoagulation therapy from older patients with atrial fibrillation. Indeed, with the increasing aging of the population, and poor therapeutic observance, there is an increased risk of hemorragic adverse effects. However, vitamin K antagonists are associated with a significant reduction in embolic events, and recent guidelines recommend their prescription for elderly patients with atrial fibrillation. Their impact on the risk of thromboembolic events is well documented, with better results than those obtained with new oral anticoagulants. Education of the patient and family, and close cooperation between the patient, family, physician and entire medical team, are essential for the safety and efficacy of this treatment.

Topics: 4-Hydroxycoumarins; Anticoagulants; Drug Monitoring; Drug Prescriptions; Humans; Indenes; Monitoring, Physiologic; Practice Patterns, Physicians'; Thrombosis; Treatment Outcome; Vitamin K

Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Humans; Leg Ulcer; Male; Thrombosis; Venous Insufficiency; Vitamin K; Warfarin

The aims of this prospective study were to identify, in vitamin K antagonist (VKA)-treated patients, factors associated with INR values: (i) greater than 6.0. and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients.. During a 6-month period, 3090 consecutive patients were referred to our Department of Internal Medicine, including 412 VKA-treated patients. At admission, the medical records of VKA-treated patients were reviewed for type, duration and indication of VKA therapy, previous medical history of VKA-related hemorrhage, comorbidities and concomitant medications.. Forty of the 412 VKA-treated patients (9.7%) exhibited oral anticoagulant related overcoagulation. VKA overcoagulation was associated with high morbidity, leading to major bleeding in 27.5% of cases; moreover, 12.5% of these patients died, death being mainly due to major bleeding. Under multivariate analysis, significant factors for VKA-related overcoagulation were as follows: previous medical history of VKA therapy-related hemorrhage (P=0.00001) and INR levels over therapeutic range (P=0.0006), chronic liver disease (P=0.03), therapy with amiodarone (P=0.009); in contrast, statin therapy was found to be a protective factor of VKA overcoagulation (P=0.008).. The knowledge of predictive factors of VKA-related overcoagulation seems of utmost importance to improve patients' management. Our study underlines the fact that the potential of drug interaction should be taken into account when choosing amiodarone for patients receiving VKAs. Interestingly, long-term (>6 month) statin therapy may be a protective factor of VKA overcoagulation. Our findings, therefore, suggest that there may be no need to switch long-term users of VKA and statin to a safer alternative therapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Interactions; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Risk Factors; Thrombosis; Vitamin K; Young Adult

Home parenteral nutrition (PN) has improved the survival of children with intestinal failure. Important complications include catheter-related thrombosis, occlusion, and infection. This study evaluated the efficacy and safety of prophylactic anticoagulation in the prevention of these complications.. Medical records were retrospectively reviewed of all children (0-18 years) with PN between January 1994 and March 2007 in 1 tertiary center. After introduction of prophylactic low molecular weight heparin or vitamin K antagonists in March 2007, all patients were prospectively followed until March 2010.. In sum, 14 patients did not receive prophylaxis; 13 switched from no prophylaxis to prophylaxis in March 2007; and 5 directly received prophylaxis. Median age of PN onset was 4 months (range, 0.1-202) in the nonprophylaxis group (n = 27) and 25 (range, 2-167) in the prophylaxis group (n = 18); 16 children received low molecular weight heparin and 2, vitamin K antagonists. Catheter-related thrombosis developed in 9 patients with no prophylaxis (33%) and 1 with prophylaxis (6%) (P = .034). Cumulative 5-year thrombosis-free survival was 48% and 93% in the nonprophylaxis and prophylaxis groups, respectively (P = .047). Per 1,000 PN days, the nonprophylaxis and prophylaxis groups had 2.6 and 0.1 occlusions (P = .04) and 4.6 and 2.1 infections (P = .06), respectively. Cumulative infection-free survival after 3 years was 19% and 46% in the nonprophylaxis and prophylaxis groups, respectively (P = .03). Bleeding complications did not occur.. Thromboprophylaxis significantly decreased catheter-related thrombosis and occlusion in children with PN without complications.

Topics: Adolescent; Blood Coagulation; Catheterization, Central Venous; Catheters; Child; Child, Preschool; Drug Evaluation; Female; Heparin, Low-Molecular-Weight; Humans; Infant; Male; Parenteral Nutrition, Home; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure.. The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement.. In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C).. Perioperative antithrombotic management is based on risk assessment for thromboembolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes.

Topics: Angioplasty, Balloon, Coronary; Aspirin; Atrial Fibrillation; Drug Administration Schedule; Elective Surgical Procedures; Evidence-Based Medicine; Fibrinolytic Agents; Heart Valve Prosthesis; Humans; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Societies, Medical; Stents; Thrombosis; United States; Vitamin K

Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered.. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.. In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C).. These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Topics: Aspirin; Catheterization; Combined Modality Therapy; Ductus Arteriosus, Patent; Evidence-Based Medicine; Fibrinolytic Agents; Heart Atria; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Mitral Valve; Platelet Aggregation Inhibitors; Postoperative Complications; Rheumatic Heart Disease; Risk Factors; Societies, Medical; Stroke; Thromboembolism; Thrombolytic Therapy; Thrombosis; Vitamin K

Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children.. The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.. We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C).. The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies.

Topics: Anticoagulants; Blood Coagulation Tests; Cardiac Catheterization; Child; Child, Preschool; Cooperative Behavior; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Interdisciplinary Communication; Platelet Aggregation Inhibitors; Renal Veins; Risk Factors; Secondary Prevention; Societies, Medical; Thrombosis; Upper Extremity Deep Vein Thrombosis; Vitamin K

New oral anticoagulants, such as dabigatran, rivaroxaban, apixaban, and edoxaban display pharmacologic and pharmacodynamic data similar to low molecular weight heparins. Peak levels are found 2-4 h after oral ingestion and elimination half-lives are in the range of 7-14 h. The drugs differ primarily concerning renal elimination. Dose adjustment is only performed in patients with impaired renal function, high risk of bleeding and patients with co-medications which influence the metabolism or anticoagulant effect of the drugs. Due to the short half-life, perioperative bridging is not necessary. Currently, no specific antidotes are available: however, assay systems are available for measuring the plasma concentration of dabigatran and rivaroxaban. In emergency cases a normal thrombin time excludes relevant levels of dabigatran, whereas a normal anti-factor Xa assay result excludes relevant levels of factor Xa inhibitors.The new anticoagulants are being used for prophylaxis of venous thrombosis in elective hip and knee surgery, as well as for treatment of venous thrombosis and for prevention of stroke and systemic embolism in patients with atrial fibrillation. Additional indications are to follow. Dabigatran is given at a dose of 110 mg initially 1-4 h after surgery followed by 220 mg once daily for prophylaxis of thrombosis and at doses of 110 mg or 150 mg twice daily for therapeutic anticoagulation. The prophylactic and therapeutic doses of rivaroxaban are 10 and 20 mg and, of apixaban 2.5 mg and 5 mg twice daily, respectively.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Humans; Stroke; Thrombosis; Vitamin K

Topics: Anticoagulants; Hemorrhage; Humans; Thrombocytopenia; Thrombosis; Vitamin K; Wounds and Injuries

Prothrombin complex concentrates (PCCs) are used for the urgent reversal of oral vitamin K antagonists in patients with life-threatening bleeding or prior to urgent procedures/surgery. PCCs offer rapid and complete reversal without the disadvantages of volume overload and adverse reactions seen with fresh frozen plasma (FFP). There is concern about the risk of thrombosis associated with the use PCCs; data on this is limited at present.. To determine the incidence of objectively confirmed arterial or venous thromboembolism within 30 days following the administration of PROTHROMBINEX®-VF (PTX-VF) to acutely reverse a prolonged INR.. A prospective observational study was conducted at two teaching hospitals in Auckland, NZ. All patients who received PTX-VF for the acute reversal of prolonged INR were eligible. Baseline patient demographics and reasons for PTX-VF administration were recorded. Patients were reviewed at days 7 and 30, to confirm/exclude thromboembolism or adverse events.. 173 patients were enrolled from August 2008 to March 2009. The most frequent indication for reversal was acute bleeding. At 30 days 4.6% (8/173) patients had a definite/probable thrombotic event, and 16.7% had died either due to the presenting bleed (intracranial haemorrhage) or a complication of their presenting complaint (e.g. sepsis, renal failure).. Acute reversal of anticoagulant therapy with PTX-VF is associated with a significant rate of thromboembolism (4.6%) within 30 days. These events can be explained by ongoing cessation of anticoagulant therapy in patients with ongoing risk factors for arterial or venous thrombosis, rather than directly attributable to PTX-VF therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Risk Factors; Thrombosis; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Azetidines; Benzylamines; France; Hemorrhage; Humans; Pulmonary Embolism; Thromboembolism; Thrombosis; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Drug Administration Schedule; Elective Surgical Procedures; Hemoglobins; Heparin; Humans; International Normalized Ratio; Postoperative Hemorrhage; Preoperative Care; Surgical Procedures, Operative; Thrombosis; Time Factors; Vitamin K

Anticoagulation with vitamin K antagonists (VKAs) is problematic because of difficulties in safely managing dosing. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase genes (VKORC1) have been shown to affect VKA dosing in adults. The association of these polymorphisms on VKA dosing in children has not been investigated. The objective of the study was to assess associations of CYP2C9 and VKORC1 polymorphisms and clinical variables on VKA dosing in children. A nonselected cohort of pediatric patients receiving VKA were tested for CYP2C9 and VKORC1 polymorphisms, and clinical data were collected. Multiple linear regression modeling was used to assess relationships of VKA dose with genetic and clinical variables. Fifty-nine patients were recruited; 55.9% were receiving warfarin, and 44.1% were on phenprocoumon. There was a negative association of age with VKA dose (P < .001). Comparing VKORC1 genotypes, the AA group required significantly lower daily doses than GG group (P = .011). In the full model including age, VKORC1 and CYP2C9 genotypes accounted for 38% of dose variation. Age explained 28.3% of VKA dose variations; VKORC1 and CYP2C9 explained only 3.7% and 0.4%, respectively. In children, the most critical factor in determining VKA dose is age. VKORC1/CYP2C9 genotypes only marginally explain dose variations.

Topics: Adolescent; Adult; Age Factors; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Child; Child, Preschool; Cohort Studies; Cytochrome P-450 CYP2C9; Genotype; Humans; Infant; Infant, Newborn; Mixed Function Oxygenases; Phenprocoumon; Polymorphism, Genetic; Prognosis; Prospective Studies; Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin; Young Adult

Patients with prosthetic heart valves have a higher risk of developing valve thrombosis and arterial thromboembolism. Antithrombotic therapy during the early postoperative period after biologic mitral valve replacement (MVR) is controversial. Hence, a retrospective study was conducted to investigate the efficacy of different antithrombotic therapies in patients after MVR with bioprostheses.. Between January 2000 and January 2006, a total of 99 patients presenting with preoperative sinus rhythm underwent isolated bioprosthetic MVR. Of these patients, 59 (58%) received a bovine pericardial xenograft, and 40 (42%) a porcine bioprosthesis. The postoperative antithrombotic therapy was prescribed according to the surgeon's preference.. Fifty-one (51%) patients received acetylsalicylic acid (ASA group, 100 mg/day), 12 (13%) did not receive any specific antithrombotic therapy (NT group), and 36 (36%) received a vitamin K antagonist (VKA group, INR 2-3). The primary endpoints were the rate of cerebral ischemic events, bleeding events, and survival. The mean follow up was 23 months (range: 3-68 months). There were five early deaths (5%), and eight late deaths (8%). There were five episodes of cerebral ischemic events; these included three patients (8.3%) in the VKA group, one patient (2.0%) in ASA group, and one patient (8.3%) in the NT group (p = 0.351). Of these episodes, two occurred between 24 h and three months after surgery. Only one (2.8%) episode of major bleeding occurred (in the VKA group), due to poor anticoagulation management.. Each of the antithrombotic therapies evaluated appeared to be safe. There was no evidence to suggest that any specific antithrombotic therapy would be superior in preventing valve thrombosis in patients undergoing bioprosthetic MVR.

Topics: Aged; Aged, 80 and over; Animals; Anticoagulants; Aspirin; Bioprosthesis; Brain Ischemia; Cattle; Chi-Square Distribution; Drug Administration Schedule; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Logistic Models; Male; Middle Aged; Mitral Valve; Practice Guidelines as Topic; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Swine; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

Warfarin is the most utilized oral anticoagulant for the long term prophylaxes of thrombosis. Its use has been increased as new clinical conditions, capable of leading to thrombosis, have been detected. Due to the special characteristics of warfarin, such as the variability of doses for each individual, the narrow margin between adequate and inadequate doses, interaction with multiple pharmaceutical products, interference of its action by vitamin K present in the diet and the possibility of hemorrhagic complications or thrombotic recurrence, this drug requires a very careful dosage and strict laboratory and clinical monitoring. Despite being in the market for more than de fifty years and its many disadvantages, warfarin has not been substituted for the new oral anticoagulants. In 1999, warfarin was positioned eleventh on the list of the most used medicines in the world.

Topics: Anticoagulants; Drug Interactions; Drug Monitoring; Food-Drug Interactions; Hemorrhage; History, 20th Century; History, 21st Century; Humans; International Normalized Ratio; Mixed Function Oxygenases; Patient Education as Topic; Thrombophilia; Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

To assess safety and feasibility of using radial artery access for percutaneous coronary intervention (PCI) in patients on oral anticoagulation without interrupting therapy.. The radial artery approach for PCI is intuitively attractive for patients receiving chronic oral anticoagulation with vitamin K antagonists (VKAs) but little data exist concerning feasibility or safety of this approach in this population. The main advantage of this strategy would be to avoid bridging therapy with heparin that increases risk of thrombotic and bleeding events.. In this prospective observational study, 50 consecutive patients referred for coronary angiography underwent PCI without interrupting oral anticoagulant therapy. The main outcome measures were bleeding and thrombotic complications.. The indications for permanent oral anticoagulation were as follows: atrial fibrillation in 62%, mechanical prosthesis in 24%, and venous thromboembolism in 14%. Seventy-two percent were elective cases and 28% presented with acute coronary syndromes. PCI was performed with an INR range of 1.4-3.4 with mean of 2.2 +/- 0.6. Seventy-six percent of the patients were on dual antiplatelet therapy before the procedure. No thrombotic events or excess bleeding were observed at 1 month. Only one patient had a minor hemorrhage 8 days after procedure.. This series suggests that for patients treated with VKAs, the use of radial artery access is feasible and safe for PCI on dual antiplatelet therapy without interrupting oral anticoagulant treatment.

Topics: Administration, Oral; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Drug Administration Schedule; England; Feasibility Studies; Female; France; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Radial Artery; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Drug Administration Schedule; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Radial Artery; Thrombosis; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Anticoagulants; Humans; Risk Assessment; Thrombosis; Vitamin K; Vitamins

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Cohort Studies; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Male; Orthopedic Procedures; Preoperative Care; Thrombosis; Treatment Outcome; Vitamin K; Warfarin; Wounds and Injuries

The vitamin K antagonists (VKA) remain to this day the only oral form of therapeutic anticoagulation. Approximately 1% of the French population, mainly elderly, is treated with these anticoagulants. Oral anticoagulants have significant risks of iatrogenic complications; indeed they are the leading cause of such drug-induced complications, predominantly hemorrhages. AFSSAPS (French Drug and Medical Products Agency) clinical practice recommendations, repeatedly disseminated, emphasize the education of patients receiving VKAs. Managing oral anticoagulant treatment is challenging, with a significant risk of under- or overdosing and consequently, thrombosis or hemorrhage. The therapeutic window is narrow, multiple drug-interactions are possible, and the specific dose required for a particular individual to achieve appropriate International Normalized Ratio (INR) levels is unpredictable. The literature contains few randomized controlled trials about the efficacy of education for patients treated with oral anticoagulants. These education programs are not standardized and are therefore varied and difficult to compare. Nevertheless, studies demonstrate the importance of patient education programs in reducing the risk of hemorrhage and achieving better treatment stability. The Grenoble region hospital-community network for vascular diseases (GRANTED) has developed an education program for these patients, consisting of individual sessions for the patient and/or a friend or family member (either at a health care facility or at the patient's home), telephone support and group sessions, and using educational tools and supports. There is also a link with the general practitioner who receives a report. This approach makes it possible to adapt the educational message to individual patients and their daily lives, as well as directly involving them in the management of their treatment.

Topics: Administration, Oral; Anticoagulants; Cooperative Behavior; Dose-Response Relationship, Drug; Hemorrhage; Humans; Interdisciplinary Communication; Medication Adherence; Nurse-Patient Relations; Patient Care Team; Patient Education as Topic; Physician-Patient Relations; Randomized Controlled Trials as Topic; Risk Factors; Social Support; Thrombosis; Treatment Outcome; Vitamin K

For more than 50 years vitamin K antagonists (VKA) have been the gold standard for long-term oral anticoagulant treatment. New anticoagulants are now in extensive clinical development what will probably have a significant impact on daily practice in the near future. Compounds that specifically block activated factor X (FXa) or activated factor II (thrombin) have entered impressive phase III trials. Idraparinux is a long-active derivative from fondaparinux (synthetic pentasaccharide) and is administered subcutaneously. It inhibits indirectly FXa. Apixaban and rivaroxaban are small molecules that directly block FXa following oral administration. Dabigatran is another substance that is administered orally and directly inhibit thrombin. This article will review the potential interest of these new drugs in the modern antithrombotic care. In the meantime, we will briefly discuss two new tools that have been developed to optimalizing the classical VKA anticoagulation: anticoagulation clinics and point-of-care testing of INR that allows self-monitoring.

Topics: Anticoagulants; Antithrombins; Factor X; Factor Xa Inhibitors; Humans; Thrombosis; Vitamin K

Topics: Aged; Area Under Curve; Blood Coagulation; Blood Coagulation Tests; Chemistry, Clinical; Female; Fibrinogen; Humans; Male; Middle Aged; Thrombelastography; Thrombosis; Vitamin K

Topics: Animals; Anticoagulants; Cattle; Clinical Competence; Humans; International Normalized Ratio; Risk Factors; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Cohort Studies; Hemorrhage; Humans; Neoplasms; Quality of Life; Recurrence; Registries; Research Design; Risk; Thrombosis; Treatment Outcome; Vitamin K

Transesophageal echocardiography (TEE) has been used to document the incidence of non-obstructive thrombosis (NOT) after mechanical prosthetic mitral valve replacement (MVR). The postoperative occurrence and unpredictable evolution of NOT complicate its management. The study aim was to examine the safety and efficacy of prolonged, combined administration of heparin and vitamin K antagonists (VKA) recommended for this indication.. All patients who underwent mechanical prosthetic MVR between July 1999 and December 2004 at the authors' institution were systematically studied with TEE immediately after surgery. Patients who presented with > or = 5 mm NOT were treated with combined heparin and VKA until TEE-confirmed resolution of the thrombus.. Among 256 patients who underwent 263 MVRs (seven reinterventions), 47 (17.9%) presenting with > or = 5 mm NOT received combined heparin and VKA for between 7 and 115 days (median 17 days). No thromboembolic or hemorrhagic events or deaths were observed during this period of observation. Four patients were treated with danaparoid and VKA because of thrombocytopenia induced by heparin before the diagnosis of NOT. Over a mean follow up of 39 months, one patient died from cancer and another from the sequelae of a stroke. In total, there were five NOT recurrences, three of which were complicated by embolic events without sequelae within eight months, and one by a recurrent stroke. In addition, three patients without demonstrable NOT recurrence suffered transient ischemic attacks.. Among this small sample of patients, combined heparin and VKA was well tolerated and effective, and could prevent reoperation or thrombolysis. These observations may warrant further study in a larger patient population.

Topics: Adult; Aged; Anticoagulants; Cause of Death; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Long-Term Care; Male; Middle Aged; Mitral Valve; Postoperative Complications; Stroke; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Drug Overdose; Factor IX; Heart Atria; Heart Diseases; Heart Ventricles; Humans; Indenes; Male; Middle Aged; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation Factors; Blood Transfusion; Clinical Trials as Topic; Factor VII; Hemorrhage; Humans; International Normalized Ratio; Prothrombin; Recombinant Proteins; Thrombosis; Time Factors; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Diagnosis, Differential; Epistaxis; Female; Hematemesis; Humans; Partial Thromboplastin Time; Pesticides; Poisoning; Prothrombin Time; Thrombosis; Unconsciousness; Vitamin K; Vitamin K Deficiency

Topics: Administration, Oral; Anticoagulants; Humans; International Normalized Ratio; Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Clinical Trials, Phase II as Topic; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin

To report a case in which the anticoagulation effect of warfarin appeared to have been potentiated by chitosan, probably due to interference with the absorption of vitamin K.. An 83-year-old male with hypertensive cardiovascular disease, type 2 diabetes mellitus, and chronic atrial fibrillation complicated by left atrial thrombus formation was maintained on warfarin 2.5 mg/day. Marked elevation of the international normalized ratio (INR) was noticed after self-medication with chitosan 1200 mg twice daily. He denied taking any other drugs, natural substances, herbal medicines, and nutritional supplements, and stated that he had not changed his dietary habits. After parenteral administration of vitamin K and discontinuation of chitosan, the INR returned to within the target range. However, the patient took chitosan again, and the INR increased to well above the target range. Following strong medical advice, the patient stopped taking chitosan, and the INR remained stable thereafter.. Chitosan is a positively charged polymer that binds to the negatively charged lipids and bile acids in the gastrointestinal tract. It can affect the absorption of vitamins A, D, E, and K. Therefore, the anticoagulation effect of warfarin may be potentiated by chitosan through this mechanism. Use of the Naranjo probability scale revealed that the adverse effect was probably due to chitosan.. The interaction between warfarin and chitosan has not previously been reported. Healthcare professionals should be aware of this potential interaction.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chitosan; Chronic Disease; Diabetes Mellitus, Type 2; Drug Synergism; Humans; Hypertension; International Normalized Ratio; Male; Self Medication; Thrombosis; Vitamin K; Vitamins; Warfarin

Topics: Administration, Oral; Anticoagulants; Electric Countershock; Heart Valve Prosthesis; Hemoglobinuria; Heparin, Low-Molecular-Weight; Humans; Medical Audit; Neoplasms; Perioperative Care; Self Administration; Thromboembolism; Thrombophilia; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Blood Coagulation; Humans; Thrombosis; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Hematologic Tests; Hemorrhage; Humans; International Normalized Ratio; Prothrombin; Quality Control; Thrombosis; Vitamin K

Topics: Clinical Trials as Topic; Cohort Studies; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Teratogens; Thrombosis; Vitamin K

All 110 Dutch orthopedic departments were sent a survey on perioperative thromboprophylaxis protocols, and 79% responded. After hip and knee replacements, all used pharmacological thromboprophylaxis: a low-molecular weight heparin (LMWH) in 87% of departments, which was most often combined with vitamin K antagonists (VKAs). LMWH was usually started preoperatively (91%). After discharge, VKAs were mostly prescribed (79%) for at least 6 weeks, and often for 3 months. 17% of departments used LMWH for 6 weeks, whereas in only 3% no post-discharge prophylaxis was given. In day-care surgery, including arthroscopies, 58% use LMWH and in short-stay surgery 80% administer LMWH during the hospital stay. Because of lack of conclusive evidence for day-care surgery, the national guidelines cannot support pharmacological prophylaxis in this setting. In general, Dutch orthopedic departments comply poorly with the national guidelines on extended thromboprophylaxis for hip and knee replacement surgery, which recommends postoperative LMWH for 6 weeks. They are divided in the use of pharmacological prophylaxis in day-care surgery.

Topics: Fibrinolytic Agents; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Netherlands; Postoperative Complications; Practice Guidelines as Topic; Surveys and Questionnaires; Thrombosis; Vitamin K

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an alpha-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.

Topics: Animals; Animals, Genetically Modified; Anticoagulants; Antigens, CD; Factor Xa; Heart Transplantation; Heparin, Low-Molecular-Weight; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; International Normalized Ratio; Ischemia; Membrane Cofactor Protein; Membrane Glycoproteins; Microcirculation; Myocardium; Papio; Primates; Prothrombin; Sirolimus; Swine; Tacrolimus; Thrombosis; Time Factors; Transplantation, Heterologous; Treatment Outcome; Vitamin K; Warfarin

Topics: Anticoagulants; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Humans; Myocardial Infarction; Thrombin; Thrombosis; Vitamin K; Warfarin

Transoesophageal echocardiography has shown a high incidence on non-obstructive thrombosis after mitral valve replacement with a mechanical prosthesis. The unpredictable outcome and the period during which the complication arises make treatment difficult. The aim of this study was to assess the tolerance and efficacy of the association of long-term heparin and oral anticoagulation, as recommended in this indication. All patients undergoing mitral valve replacement with a mechanical prosthesis between June 1999 and July 2001 were systematically included and studied by transoesophageal echocardiography in the immediate postoperative period. Those with non-obstructive thrombosis at least 5 mm in size were treated by heparin and oral coagulation until the thrombus disappeared on transoesophageal echocardiography. One hundred and fourteen patients undergoing 120 mitral valve replacements (6 reoperations) underwent transoesophageal echocardiography and non-obstructive thrombi measuring at least 5 mm were found on 26 occasions (21.7%). The association of heparin and oral coagulation was maintained for 7 to 115 days (average 20 days). No thromboembolic or haemorrhagic complications and no deaths were observed during this period. Two patients were treated with danaparoid and oral anticoagulation because of heparin-induced thrombocytopenia before the diagnosis. None of the patients died during follow-up (average 49 months); there were 4 recurrent non-obstructive thromboses, three of which were complicated by thromboembolic events with no sequellae in the first 8 months, again treated effectively with the association of heparin and oral anticoagulants; two cerebral embolic events without sequellae were observed without a demonstrable non-obstructive thrombus on transoesophageal echocardiography. The authors conclude that the association of heparin and oral anticoagulants seems well tolerated and effective in this small population and this would justify a large scale clinical trial.

Topics: Adult; Aged; Anticoagulants; Aspirin; Drug Therapy, Combination; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Male; Middle Aged; Mitral Valve; Retrospective Studies; Thrombosis; Treatment Outcome; Vitamin K

Topics: Animals; Blood Platelets; c-Mer Tyrosine Kinase; Humans; Intercellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Platelet Activation; Platelet Aggregation Inhibitors; Protein Processing, Post-Translational; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Signal Transduction; Thrombosis; Vitamin K

The new oral direct thrombin inhibitor ximelagatran is at least equivalent to warfarin for stroke prevention in patients with non-valvar atrial fibrillation, and seems to be a promising adjunct to aspirin after acute coronary syndrome

Topics: Administration, Oral; Anticoagulants; Antithrombins; Azetidines; Benzylamines; Humans; Thrombosis; Vitamin K; Warfarin

Calcification is a common complication in cardiovascular disease and may affect both arteries and heart valves. Matrix gamma-carboxyglutamic acid (Gla) protein (MGP) is a potent inhibitor of vascular calcification, the activity of which is regulated by vitamin K. In animal models, vitamin K antagonists (oral anticoagulants [OACs]) were shown to induce arterial calcification. To investigate whether long-term OAC treatment may induce calcification in humans also, we have measured the grade of aortic valve calcification in patients with and without preoperative OAC treatment. OAC-treated subjects were matched with nontreated ones for age, sex, and disease. Calcifications in patients receiving preoperative OAC treatment were significantly (2-fold) larger than in nontreated patients. These observations suggest that OACs, which are widely used for antithrombotic therapy, may induce cardiovascular calcifications as an adverse side effect.

Topics: Administration, Oral; Aged; Anticoagulants; Aortic Valve; Calcinosis; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Risk Factors; Thrombosis; Vitamin K

Topics: Anticoagulants; Aspirin; Atrial Appendage; Atrial Fibrillation; Blood Loss, Surgical; Carotid Arteries; Dalteparin; Drug Administration Schedule; Elective Surgical Procedures; Filtration; Heart Valve Prosthesis Implantation; Humans; International Normalized Ratio; Intraoperative Care; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Premedication; Stents; Thromboembolism; Thrombosis; Vitamin K; Warfarin

Although the central role of thrombin in arterial thrombosis is well established, the efficacy of vitamin K-dependent factor depletion by warfarin at preventing this process has not been established. To assess the efficacy of warfarin in the prevention of arterial thrombosis, two intensities of anticoagulation were compared in a well-characterized porcine model of carotid angioplasty. For 10 days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low-dose warfarin plus aspirin (n = 9), or control tablets (n = 10). Injured arteries were assessed for (111)In-platelet ( x 10(6) cm(-2)) and (125)I-fibrin(ogen) (molecules x 10(12) cm(-2)) deposition and the incidence of macroscopic thrombus. Platelet (30 +/- 7 vs. 332 +/- 137; P = 0.001) and fibrinogen (156 +/- 17 vs. 365 +/- 90; P < 0.05) deposition were significantly reduced in animals receiving high-intensity warfarin whereas low-intensity warfarin/ASA (520 +/- 240 and 1193 +/- 638) was similar to control (P =NS). At the time of angioplasty, the PT-INR and vitamin K-dependent factors varied over a broad range. The greatest reduction of platelet and fibrinogen deposition occurred as the PT-INR increased from 1.0 to 2.2. Increasing the PT-INR beyond 3.0 resulted in little, if any, incremental reduction of either platelet or fibrinogen deposition. Macroscopic thrombus was abolished at PT-INR > 2.2. Despite a broad range of vitamin K factor activities, no single factor was predictive of either platelet or fibrinogen deposition. Warfarin at PT-INR > 2.2 effectively eliminates thrombosis following deep arterial injury. Arterial thrombosis correlates poorly with any single vitamin K-dependent factor but rather appears to be a function of the entire extrinsic coagulation pathway as measured by the PT-INR.

Topics: Angioplasty; Animals; Arteries; Aspirin; Blood Coagulation Factors; Blood Platelets; Dose-Response Relationship, Drug; Fibrinogen; International Normalized Ratio; Platelet Adhesiveness; Swine; Thrombosis; Vitamin K; Warfarin

This study was undertaken to evaluate the risks and pregnancy outcome in women with prosthetic heart valves on different anticoagulent regimens.. A retrospective chart review of 82 pregnancies in 33 women with mechanical valve prostheses at a tertiary referral center from 1987 to 2002. The main outcome measures were major maternal complications and perinatal outcome.. The valve replaced was mitral (60.6%), aortic (18.2%), and both (21.2%). Fifty-four pregnancies (65.9%) resulted in live births, 9 (11.0%) had stillbirths (all on warfarin), and 12 (14.6%) had spontaneous and 7 (8.5%) therapeutic abortions (all on warfarin). The rate of spontaneous abortion was highest in women on warfarin throughout pregnancy (P < .01). The live birth rate was higher in women on heparin compared with those on warfarin (P < .01), and in those on heparin/warfarin compared with warfarin alone (P < .01). There were no maternal deaths; however, 3 patients had mitral valve thrombosis (2 on heparin and 1 on warfarin) necessitating surgery in 1 patient and medical thrombolysis in 2 patients. Hemorrhagic complications occurred in 5 patients, 4 of whom required transfusion.. No single anticoagulant regimen confers complete protection from thromboembolic phenomena in pregnancy. Despite a high maternal morbidity rate, the perinatal outcome is acceptable when pregnancy progresses beyond the first trimester.

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Birth Weight; Delivery, Obstetric; Female; Fetal Death; Fetal Growth Retardation; Gestational Age; Heart Valve Prosthesis; Heparin; Humans; Mitral Valve; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies; Thrombosis; Vitamin K; Warfarin

Topics: 1-Carboxyglutamic Acid; Animals; Anticoagulants; Bone and Bones; Dietary Supplements; Humans; Liver; Osteocalcin; Risk; Thrombosis; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Risk Factors; Thromboembolism; Thrombosis; Vitamin K

Topics: Anticoagulants; Celiac Disease; Diagnosis, Differential; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Thromboplastin; Thrombosis; Vitamin K

In this Minisymposium three principles for anticoagulant therapy are discussed and examples of novel, selective coagulation inhibitors at the stage of advanced clinical trials are given. This introduction attempts to explain the different mechanisms of action on a broad scale, and also includes a brief look at effects on inflammation and cancer.

Topics: Anti-Inflammatory Agents; Anticoagulants; Antineoplastic Agents; Blood Coagulation; Heparin; Heparin, Low-Molecular-Weight; Humans; Inflammation; Neoplasms; Thrombin; Thrombosis; Vitamin K

Trousseau described spontaneous, recurrent superficial migratory thrombophlebitis associated with occult cancers, and this was later correlated with disseminated microangiopathy (platelet-rich clots in small blood vessels). Trousseau syndrome often occurs with mucinous adenocarcinomas, which secrete abnormally glycosylated mucins and mucin fragments into the bloodstream. Since carcinoma mucins can have binding sites for selectins, we hypothesized that selectin-mucin interactions might trigger this syndrome. When highly purified, tissue-factor free carcinoma mucin preparations were intravenously injected into mice, platelet-rich microthrombi were rapidly generated. This pathology was markedly diminished in P- or L-selectin-deficient mice. Heparin (an antithrombin-potentiating agent that can also block P- and L-selectin recognition of ligands) ameliorated this platelet aggregation, but had no additional effect in P- or L-selectin-deficient mice. Inhibition of endogenous thrombin by recombinant hirudin also did not block platelet aggregation. Mucins generated platelet aggregation in vitro in hirudinized whole blood, but not in platelet-rich leukocyte-free plasma nor in whole blood from L-selectin-deficient mice. Thus, Trousseau syndrome is likely triggered by interactions of circulating carcinoma mucins with leukocyte L-selectin and platelet P-selectin without requiring accompanying thrombin generation. These data may also explain why heparin ameliorates Trousseau syndrome, while vitamin K antagonists that merely depress thrombin production do not.

Topics: Adenocarcinoma, Mucinous; Animals; Antifibrinolytic Agents; Blood Platelets; Comorbidity; Fibrinolytic Agents; Heparin; Humans; L-Selectin; Lung; Mice; Mice, Inbred C57BL; Mucins; Neoplasm Transplantation; P-Selectin; Paraneoplastic Syndromes; Platelet Activation; Syndrome; Thrombin; Thrombophlebitis; Thrombosis; Transplantation, Heterologous; Tumor Cells, Cultured; Vitamin K

To determine whether warfarin can be safely administered to children who require long-term total parenteral nutrition (TPN), for the purpose of preventing central venous access device (CVAD)-related thrombosis.. A prospective cohort study was conducted of 8 children with short-gut syndrome or small intestinal anomalies. All patients received oral anticoagulant therapy (warfarin) managed by the hematology department at a tertiary pediatric center. Data collected included demographic details, nutritional intake, age, weight, history of deep vein thrombosis, number and functional duration of CVADs, warfarin requirements, and adverse event rates.. A total of 15.2 warfarin years were studied prospectively. The target therapeutic range was achieved 51.1% of time. The mean dose of warfarin required to achieve the target therapeutic range (international normalized ratio) of 2.0 to 3.0 was 0.33 mg/kg/d. The mean duration between warfarin monitoring tests was 6.6 days. The median vitamin K intake per patient was 0.367 mg/kg/d (range: 0.018-2.85 mg/kg/d). Before commencing anticoagulant therapy, the mean CVAD duration was 160.9 days. Concomitant warfarin therapy was associated with a mean CVAD duration of 351.7 days. There were no major bleeding events, and no clinical extension of thrombosis was observed.. This is the first published study to report uniform warfarin prophylaxis for CVADs in children. Warfarin therapy can be administered safely in children who require long-term TPN. Warfarin prophylaxis seems to prolong CVAD survival.

Topics: Adolescent; Anticoagulants; Catheterization, Central Venous; Child; Child, Preschool; Cohort Studies; Congenital Abnormalities; Drug Evaluation; Female; Hemorrhage; Humans; International Normalized Ratio; Intestine, Small; Male; Parenteral Nutrition, Total; Prospective Studies; Safety; Short Bowel Syndrome; Thrombosis; Vitamin K; Warfarin

The optimal duration of oral anticoagulant therapy for patients with a first episode of deep vein thrombosis (DVT) is still a matter of debate. However, according to the ACCP consensus strategy a limited stratification in treatment duration is advocated, i.e. 3 months for patients with a transient risk factor and 1 year or longer for patients with recurrent disease or a consistent risk factor such as thrombophilia or cancer. This consensus strategy is founded on the mean optimal duration of therapy obtained in large cohorts of patients and is mainly based on the risk of recurrent venous thromboembolism (VTE), with only minimal consideration for the patient's bleeding risk.. The aim of this study is to optimize the anticoagulant treatment strategy with vitamin K antagonists for the individual patient with DVT.. Based on an extensive literature study, a mathematical model was constructed to balance the risk of recurrent VTE against the risk of major hemorrhagic complications. The following parameters are incorporated in the model: baseline estimates and risk factors for recurrent VTE and bleeding, clinical course of DVT, and efficacy of treatment with vitamin K antagonists. With the use of these parameters, the risk for a recurrent VTE and a bleeding episode can be calculated for the individual patient. The optimal duration of anticoagulant therapy can be defined as the timepoint at which the benefit of treatment (prevention of VTE) is counterbalanced by its risk (bleeding).. How long a patient should receive anticoagulant treatment is a matter of balancing the benefits and risks of treatment. The model shows that the optimal treatment duration varies greatly from patient to patient according to the patient's unique bleeding and recurrence risk.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Drug Therapy, Computer-Assisted; Female; Hemorrhage; Humans; Male; Middle Aged; Models, Theoretical; Recurrence; Risk; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Blood Platelets; Humans; Indenes; Neoplasms; Survival Analysis; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Hemorrhage; Heparin; Humans; Indenes; Morbidity; Thrombocytopenia; Thrombosis; Vitamin K

In this article we report the effects of low and high fat diets on the arterial thrombosis tendency in rats. The animal system used was the aorta loop model, in which we compared the effect of saturated (hardened coconut oil, HCO) and unsaturated (sunflower seed oil, SSO; corn oil, CO) fatty acids on the arterial thrombosis tendency at high fat intake (50 energy%, 45 energy% of which was either HCO, SSO, or CO). Under these conditions both SSO and CO had a beneficial effect (relative to HCO) on the arterial thrombosis tendency. In a subsequent study we compared these high fat diets with a low fat diet (5 energy%). As compared with the low fat diet, only CO significantly decreased the thrombosis risk. Serum vitamin K and triglycerides had decreased substantially after the CO diet, and to a much lesser extent after the SSO diet. It is concluded that corn oil may have a mildly anticoagulant effect, the potential benefit of which is discussed.

Topics: Animals; Anticoagulants; Arteries; Biological Transport; Corn Oil; Dietary Fats; Fatty Acids; Fatty Acids, Unsaturated; Male; Rats; Rats, Wistar; Thrombosis; Triglycerides; Vitamin K

Topics: Anticoagulants; Dose-Response Relationship, Drug; Hemorrhage; Humans; International Normalized Ratio; Thrombosis; Vitamin K; Warfarin

To investigate the relationship among lipids, coagulation and thrombosis in the absence of atherosclerosis, spontaneous or dietary-induced hyperlipidemic (FHL) rats were studied. FHL showed higher levels of coagulation factors VII, IX, X, VIII and XII and a shortening of the occlusion time (OT) of an artificial arterial prosthesis as compared with normolipidemic (FNL) animals. Damage of abdominal aorta of FHL was followed by increased fibrin deposition in the vascular intima as compared to FNL. After 5 months of cholesterol-rich diet FNL showed increased cholesterol, triglycerides and factor II, VII, IX, X, XII levels. A significant shortening of the OT and increased fibrin deposition was also observed. Two-month diet withdrawal restored the initial condition. Warfarin treatment, at a dose decreasing vitamin K-dependent factor to levels found in FNL, prolonged the OT and reduced fibrin deposition, without modifying F XII or changing lipid profile. An increase in the activated form of F VII was observed. In contrast, no difference was found in F VII clearance. High lipid levels favour the process of thrombus formation by increasing the activation of vitamin K-dependent coagulation factors. Low-dose warfarin treatment reverts the prothrombotic effect of hyperlipidemia.

Topics: Administration, Oral; Animals; Anticoagulants; Aorta, Abdominal; Aortic Diseases; Blood Coagulation Factors; Blood Vessel Prosthesis; Cholesterol, Dietary; Diet, Atherogenic; Disease Models, Animal; Enzyme Activation; Factor VII; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Postoperative Complications; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Thrombophilia; Thrombosis; Vitamin K; Warfarin

Vitamin K2(K2), a therapeutic agent osteoporosis, is prohibited for patients with thrombosis who are receiving warfarin (WF). However, because some aged patients with thrombosis have osteoporosis, some patients treated with WF may be administered K2 concomitantly. We investigated here the interaction between K2 and WF on thrombosis in a rat aorta loop model. Administration of WF at 0.58, 0.82 and 1.16 mg/l in drinking water for 7 days decreased the thrombotic rate and increased the death rate, dose-dependently. Therefore in the following study, 0.80 mg/l of WF was used. After 2 days of WF-treatment, 1.5, 14 and 145 mg/kg of K2 was administered for 5 days. The blood coagulation time was markedly prolonged by WF treatment for 7 days and this effect was completely inhibited by all doses of K2. WF treatment significantly decreased the cumulative thrombotic rate for 5 days. Administration of 1.5 and 14 mg/kg of K2 did not influence the WF effect on thrombosis. The thrombotic rate in the 145 mg/kg K2 group was lower than that in the WF-control group, but similar to that in the WF-untreated group. These findings suggest that high dose of K2 reduces the effect of WF on thrombosis but does not enhance the occurrence of thrombosis more than that without WF treatment.

Topics: Animals; Aortic Diseases; Drug Interactions; Male; Rats; Rats, Sprague-Dawley; Thrombosis; Vitamin K; Warfarin

We evaluated the contributions of coagulation factors IIa (thrombin) and Xa to small-diameter prosthetic graft thrombogenicity in vivo.. Preclotted and nonpreclotted (collagen-coated) polyester grafts were studied before and 24 hours after implantation into pig femoral arteries. After incubation of explanted grafts was performed with plasma depleted of vitamin K-dependent coagulation factors by barium chloride adsorption (Ba-plasma), graft-associated thrombin activity was determined by radioimmunoassay for fibrinopeptide A. Fibrinopeptide A levels reflect thrombin-mediated fibrin formation. Factor Xa activity was characterized by measuring activation of prothrombin added to Ba-plasma.. Thrombin and factor Xa were associated with the luminal surfaces of preclotted grafts before and 24 hours after implantation. Nonpreclotted grafts had negligible procoagulant activity before implantation. After 24 hours in vivo graft-associated factor Xa activity was similar in both nonpreclotted and preclotted grafts; however, more thrombin was bound to nonpreclotted coated grafts (p < 0.01).. The procoagulant activity of small-diameter prosthetic grafts persists for 24 hours after implantation and is attributable not only to graft-associated thrombin but also to de novo thrombin elaboration induced by factor Xa. Moreover, graft-associated procoagulant activity is not dependent on preclotting because it develops on nonpreclotted, collagen-coated grafts as well. Treatment strategies to attenuate graft thrombosis may require the inhibition of both thrombin and factor Xa.

Topics: Adsorption; Animals; Barium Compounds; Blood Coagulation; Blood Vessel Prosthesis; Chlorides; Collagen; Factor Xa; Femoral Artery; Fibrin; Fibrinopeptide A; Graft Occlusion, Vascular; Polyesters; Polyethylene Terephthalates; Prosthesis Design; Prothrombin; Surface Properties; Swine; Thrombin; Thrombosis; Vitamin K

Topics: Aged; Aged, 80 and over; Anticoagulants; Diet; Female; Humans; Male; Middle Aged; Phenprocoumon; Thrombosis; Vitamin K

Vitamin K is involved in the biosynthesis of a number of blood coagulation factors and bone proteins. It has been suggested that the vitamin K requirement of bone tissue is higher than that of the liver. Here we report that in rats very high doses of vitamin K affected neither the blood coagulation characteristics nor the blood platelet aggregation rate. This was observed for both phylloquinone and menaquinone-4. Both vitamers were also tested for their effects on the arterial thrombosis tendency in the rat aorta loop model. The mean obstruction times were prolonged at a high intake of menaquinone-4 (250 mg/kg body weight/day), and shortened after a similarly high phylloquinone regimen. Since (a) both vitamers only differ in their aliphatic side chains; and (b) a similar trend was observed after administration of phytol and geranylgeraniol, we conclude that the modulation of the arterial thrombosis tendency is accomplished by the side chain of vitamin K.

Topics: Animals; Blood Coagulation; Diet; Dietary Fats, Unsaturated; Disease Models, Animal; Disease Susceptibility; Diterpenes; Dose-Response Relationship, Drug; Male; Phytol; Platelet Aggregation; Rats; Rats, Wistar; Thrombosis; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

Vitamin K is required to convert specific glutamyl residues in a limited number of proteins to gamma-carboxyglutamyl residues. The response of various measures of vitamin K insufficiency to the administration of 1 mg/d of the vitamin K antagonist warfarin was studied in two groups of nine older (55-75 y) or younger (20-28 y) subjects. The most consistent and extensive alteration was an increase in the concentration of serum under-gamma-carboxylated osteocalcin followed by increased immunochemical detection of plasma under-gamma-carboxylated prothrombin (PIVKA-II), and by a decreased urinary excretion of gamma-carboxyglutamic acid. Plasma concentrations of prothrombin were altered by this treatment but prothrombin times, factor VII activity, prothrombin F-1 x 2 concentrations, and a less sensitive assay for under-gamma-carboxylated prothrombine were not. The concentration of serum under-gamma-carboxylated osteocalcin was lower when subjects consumed 1 mg vitamin K/d than when they consumed their normal diet.

Topics: 1-Carboxyglutamic Acid; Adult; Aged; Anticoagulants; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Humans; Incidence; Male; Middle Aged; Osteocalcin; Prothrombin; Thrombosis; Vitamin K; Vitamin K 1; Warfarin

The finding of cardiac failure in a neonate led to the diagnosis of congenital mitral regurgitation complicating dystrophic valves. After failed surgical valvuloplasty, the child underwent mitral valve replacement with a Saint-Jude medical prosthesis at the age of 4 months. The child developed four episodes of prosthetic valve thrombosis in the two years that followed. The first was treated surgically but the three others were treated by thrombolysis associating plasminogen tissue activator and urokinase. All but one of the thromboses occurred in a context of recent destabilisation of oral anticoagulant therapy despite the initiation of heparin. Repeat thrombolysis was successfully undertaken, thereby widening the indications of this type of treatment in the infant. This case also underlines the difficulties of oral anticoagulants in infants.

Topics: 4-Hydroxycoumarins; Anticoagulants; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Indenes; Infant; Mitral Valve; Recurrence; Thrombolytic Therapy; Thrombosis; Vitamin K

Topics: Acute Disease; Anticoagulants; Heparin; Humans; Thrombosis; Vitamin K

Topics: Anticoagulants; Hemorrhage; Humans; Risk Assessment; Thrombosis; Vitamin K

Budd-Chiari syndrome with or without portal thrombosis occurring during paroxysmal noctural hemoglobinuria is a complication with poor prognosis. We report the case of a 17-year-old woman with a double portal and hepatic venous thrombosis revealing a paroxysmal noctural hemoglobinuria and regressive with heparin. Our case suggests that the early diagnosis of the thrombosis with ultrasonography and Doppler, and rapidly initiated anticoagulant treatment may improve the prognosis of this disease.

Topics: 4-Hydroxycoumarins; Adolescent; Anticoagulants; Budd-Chiari Syndrome; Female; Hemoglobinuria, Paroxysmal; Heparin; Humans; Indenes; Portal Vein; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Disseminated Intravascular Coagulation; Drug Interactions; Heparin; Humans; Thrombosis; Vitamin K

To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgkin's lymphoma. Patients received either weekly (standard dose group) or daily (high dose group) vitamin K supplements with their total parenteral nutrition. By day 14 there had been a significant drop in protein C activity (mean of 95% of normal to 52%), protein C antigen (mean of 105% of normal to 70%), and antithrombin 3 activity (111% of normal to 83%), and an increase in fibrinogen (471-621 mg/dl) and tissue plasminogen activator (6.9-13.8 ng/ml). No changes were seen in free or total protein S, plasminogen activator inhibitor, prothrombin time or partial thromboplastin time. The decreases in protein C and antithrombin 3 persisted through day 28 after transplantation. The drop in protein C correlated strongly with decrease in serum albumin, suggesting impaired synthesis of these proteins by the liver. No differences were seen in any of these parameters between the standard and high dose groups. Deficiencies in anticoagulant proteins antithrombin 3 and protein C and a rise in fibrinogen without a concomitant improvement in fibrinolytic variables create a potentially hypercoagulable state which may contribute to the thrombotic complications of autologous BMT.

Topics: Adult; Antithrombin III; Blood Coagulation; Bone Marrow Transplantation; Dose-Response Relationship, Drug; Hodgkin Disease; Humans; Injections, Intravenous; Liver; Lymphoma, Non-Hodgkin; Protein C; Protein C Deficiency; Serum Albumin; Thrombosis; Transplantation, Autologous; Vitamin K

Anticoagulation instability due to a change in intake of vitamin K after dietary modification was observed in 2 patients on long-term oral anticoagulants. One patient developed diffuse bruises treated conservatively with fresh frozen plasma transfusion and the other had a thrombosed aortic prosthesis which required emergency operation. To prevent such complications, dietary modification especially with food rich in vitamin K should be undertaken with care in patients on long-term oral anticoagulants.

Topics: Adult; Aortic Valve; Blood Coagulation; Diet; Drug Interactions; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Skin Diseases; Thrombosis; Vitamin K; Vitamin K Deficiency; Warfarin

Two experimental thrombosis models in rats have been compared with regard to the composition of the formed thrombi and the effects of various treatments on thrombus formation. In the first model thrombosis is induced in the vena cava by a combination of venous stasis and hypercoagulability; these thrombi consist merely of red cells and fibrin with only a few platelets. In the second model thrombosis is induced in an arterio-venous shunt in which the formed thrombi consist of red cells, fibrin and a large amount of platelet aggregates adhering to the foreign material. Antiplatelet serum and acetylsalicylic acid, which reduce blood platelet activity, inhibited thrombus formation only in the arteriovenous shunt model. Dicumoxane, an oral anticoagulant, was active in both models. The glycosaminoglycans heparin, Org 10172, Fragmin and the pentasaccharide, representing the AT-III binding sequence of heparin, were active in both models. However, there were qualitative and quantitative differences between the effects of the glycosaminoglycans suggesting differences in their modes of action.

Topics: Animals; Arteriovenous Shunt, Surgical; Aspirin; Blood Coagulation Factors; Blood Platelets; Chondroitin Sulfates; Coumarins; Dermatan Sulfate; Disease Models, Animal; Fibrin; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Immune Sera; Ligation; Male; Oligosaccharides; Rats; Thrombosis; Venae Cavae; Vitamin K

Topics: Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Thrombosis; Vitamin K

This solid-phase colorimetric microtiter-plate clotting assay is much more sensitive than standard clotting tests. In enzyme-linked coagulation assay (ELCA), enzyme-labeled fibrinogen and solid-phase fibrinogen are the substrate for thrombin generated in the clotting cascade. We used this assay to measure the factors of the extrinsic pathway by an extrinsic pathway-specific assay (EP-ELCA) and to determine the individual factors of the extrinsic pathway (VII, X, V, II) in plasmas of coumadin-treated and heparin-treated patients, with prothrombin time (PT) values used as a reference. In the ELCA method, samples and controls are incubated on the same plate, eliminating the requirement for pre-standardization of the substrate "plasma" before the factor assay is done. Concentrations of factors are determined by serially diluting sample and control plasmas to yield equivalent activity at given dilutions, a more direct approach for measuring specific factors than determining log concentrations vs log clotting time. Changes in the concentrations of clotting factors are seen before changes are apparent by PT. For coumadin-treated patients, all vitamin K-dependent factors were significantly (P less than or equal to 0.001) less than in normal controls, whereas factor V concentrations were normal, as expected. For patients treated with heparin, concentrations of factors X and VII were less than in normal controls (P less than 0.01) and results for EP-ELCA, II, and V assays were normal. This methodology can readily be automated.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation Factors; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor V; Factor VII; Factor X; Fibrinogen; Heparin; Humans; Male; Peroxidase; Prothrombin; Prothrombin Time; Thrombosis; Vitamin K; Warfarin

Vascular endothelium plays an active role in preventing blood clot formation in vivo. One mechanism by which prevention is achieved involves a cell surface thrombin-binding protein, thrombomodulin, which converts thrombin into a protein C activator. Activated protein C then functions as an anticoagulant by inactivating two regulatory proteins of the coagulation system, factors Va and VIIIa. The physiological relevance of the protein C anticoagulant pathway is demonstrated by the identification of homozygous protein C--deficient infants with severe thrombotic complications. Recent studies suggest that this pathway provides a link between inflammation and coagulation.

Topics: Animals; Blood Coagulation; Chemical Phenomena; Chemistry; Glycoproteins; Homeostasis; Humans; Liposomes; Papio; Protein C; Protein S; Receptors, Cell Surface; Receptors, Thrombin; Shock, Septic; Thrombin; Thrombosis; Vitamin K

Topics: Adult; Aged; Female; Hip Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Thrombosis; Vitamin K

Topics: Anticoagulants; Hemostasis; Humans; Prothrombin Time; Quality Control; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Humans; Indenes; Reference Standards; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Aged; Anticoagulants; Female; Fibrinolytic Agents; Heparin; Humans; Indenes; Male; Middle Aged; Phlebography; Prognosis; Pulmonary Embolism; Recurrence; Thrombosis; Vitamin K

Topics: Anticoagulants; Hemostasis; Humans; Prothrombin Time; Quality Control; Thrombosis; Vitamin K

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation Tests; Heparin; Humans; Partial Thromboplastin Time; Platelet Aggregation; Prothrombin Time; Rabbits; Thromboembolism; Thromboplastin; Thrombosis; Vitamin K; Warfarin

Protein C, discovered by Stenflo in 1976, plays a major role in the regulation of thrombogenic processes. Even moderate deficiencies (0.40 to 0.60 U/ml) can be responsible for serious thromboembolic accidents. The authors evaluated the kits for the immunological assay of protein C, produced by Laboratoire Diagnostica Stago: a immuno-enzymatic method (ELISA) and Laurell's method. Despite the very different characteristics in terms of practicability, threshold of sensitivity and precision, the authors obtained an excellent correlation between these two techniques. The concentrations of protein C Ag obtained in 22 normal plasmas were 0.70 to 1.40 U/ml. In 32 patients with recurrent thrombosis with no apparent cause, 5 had a concentration of protein C Ag less than 0.70 U/ml. The identification of a deficiency of protein C Ag (Vitamin K depend protein) is often made difficulty by the fact that the patients are treated with anti-vitamin K drugs. The ratio between the vitamin K depend pro-coagulation factors and Protein C Ag may provide information about a possible deficiency.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Humans; Immunoassay; Immunoelectrophoresis; Indenes; Male; Middle Aged; Protein C; Recurrence; Thromboembolism; Thrombosis; Vitamin K

Oral anticoagulation is sometimes unjustly referred to as a particularly difficult form of antithrombotic therapy. Apparent failures of this treatment may be caused by insufficient information on the part of either the physician or the patient himself, poor standardization of laboratory tests and/or inadequate dosage of vitamin K antagonists. Specialized centers for treatment of thrombosis have done pioneer work in standardizing and evaluating oral anticoagulant treatment with respect to various indications. Based on this experience, optimum long-term anticoagulant therapy is today possible even in a small hospital or in general medical practice, provided that the pharmacological peculiarities of vitamin K antagonists and international developments concerning standardization of the prothrombin time (Quick test) and its modifications (International Normalized Ratio, INR) are taken into consideration. Regular internal and external quality control of laboratory tests for monitoring of oral anticoagulation is of the utmost importance.

Topics: Acenocoumarol; Anticoagulants; Blood Coagulation; Humans; Phenprocoumon; Quality Assurance, Health Care; Switzerland; Thrombosis; Time Factors; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Blood Coagulation; Disseminated Intravascular Coagulation; Humans; Indenes; Thrombosis; Vitamin K

A mechanized factor X assay was tested in 2222 plasma samples of patients being treated with oral anticoagulants. The correlation coefficient between this assay and Thrombotest was 0.78. The therapeutic range for factor X amidolytic activity was 150 to 300 units/l. Amidolytic factor X activity and Thrombotest provide similar information about the state of anticoagulation within the same patient, including patients that are not well balanced. The ranges for factors II, VII, IX and X clotting activity in 57 patients on long-term therapy (Thrombotest within the therapeutic range between 190 and 95 s) were 80-300, 70-600, 40-420 and 50-330 units/l, respectively. The range for factor X amidolytic activity in this group of patients was 150-470 units/l.

Topics: Anticoagulants; Blood Coagulation Tests; Factor IX; Factor VII; Factor X; Humans; Long-Term Care; Prothrombin; Prothrombin Time; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Heart Valve Prosthesis; Humans; Indenes; Postoperative Complications; Thrombosis; Vitamin K

Some aspects of the use of anticoagulants to prevent or treat thromboembolic disorders remain controversial after more than 40 years of clinical trial and experience. This review describes the mode of action of heparin and the oral anticoagulants and examines their practical use for the prevention and treatment of venous thromboembolism.

Topics: Administration, Oral; Anticoagulants; Drug Administration Schedule; Drug Interactions; Female; Hemorrhage; Heparin; Humans; Injections, Intravenous; Middle Aged; Pregnancy; Pulmonary Embolism; Thromboembolism; Thrombosis; Vitamin K; Warfarin

Topics: Aged; Antithrombin III; Antithrombin III Deficiency; Female; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Pedigree; Thrombosis; Vitamin K

Topics: Anticoagulants; Female; Heparin; Humans; Platelet Aggregation; Pregnancy; Prothrombin Time; Thrombosis; Time Factors; Vitamin K

Topics: Adult; Aged; Anticoagulants; Fibrinolytic Agents; Heparin; Humans; Middle Aged; Thrombosis; Vitamin K

Topics: 4-Hydroxycoumarins; Drug Evaluation; Humans; Indans; Indenes; Thrombosis; Time Factors; Vitamin K

In a 7 year-old girl presenting with nephrotic syndrome and repeated episodes of thrombosis, a decrease in antithrombin III and in vitro inactivity of heparin were observed. Treatment by vitamin K antagonists prevented further thromboembolic episodes.

Topics: Antithrombin III Deficiency; Child; Female; Humans; Nephrotic Syndrome; Recurrence; Thrombosis; Vitamin K

Topics: Coumarins; Dicumarol; Heparin; Humans; Indans; Platelet Aggregation; Thrombosis; Vitamin K

Topics: Anticoagulants; Heparin; Humans; Thrombosis; Vitamin K

Topics: Acenocoumarol; Anti-Inflammatory Agents; Anticoagulants; Drug Evaluation; Humans; Phenprocoumon; Platelet Aggregation; Thrombosis; Vitamin K; Warfarin

Topics: Adult; Anticoagulants; Aspirin; Dipyridamole; Drug Combinations; Female; Heart Valve Prosthesis; Humans; Platelet Adhesiveness; Platelet Aggregation; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Thrombosis; Vitamin K

Topics: Angina Pectoris; Anticoagulants; Arterial Occlusive Diseases; Arteriosclerosis; Coumarins; Disseminated Intravascular Coagulation; Fibrinolytic Agents; Heparin; Humans; Myocardial Infarction; Pulmonary Embolism; Streptokinase; Thromboembolism; Thrombophlebitis; Thrombosis; Urokinase-Type Plasminogen Activator; Vitamin K

Topics: Arteriosclerosis; Blood Platelets; Coronary Disease; Fibrinolytic Agents; Humans; Myocardial Infarction; Terminology as Topic; Thrombosis; Vitamin K

Topics: Acute Disease; Aged; Anticoagulants; Blood Cell Count; Blood Glucose; Embolism; Heart Diseases; Hemorrhage; Heparin; Humans; Male; Myocardial Infarction; Nitrogen; Rupture, Spontaneous; Thrombosis; Vitamin K

Topics: Aged; Anticoagulants; Coronary Care Units; Coronary Disease; Female; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Statistics as Topic; Streptokinase; Thrombosis; Vitamin K

Topics: Adult; Aged; Anticoagulants; Autopsy; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Thrombosis; Vitamin K

Topics: Anticoagulants; Factor IX; Factor VIII; Factor X; Heparin; Humans; Thrombosis; Vitamin K

Topics: Child; Coumarins; Heparin; Humans; Iliac Vein; Male; Necrosis; Obesity; Prognosis; Skin Diseases; Streptokinase; Thrombosis; Vitamin K

Topics: Blood Coagulation; Blood Coagulation Disorders; Embolism; Factor X; Heparin; Humans; Injections, Subcutaneous; Postoperative Complications; Thromboembolism; Thrombosis; Urogenital System; Vitamin K

Topics: Down Syndrome; Hematocrit; Hemorrhage; Humans; Infant, Newborn; Prothrombin; Thrombosis; Vitamin K

Topics: Diet Therapy; Ethyl Biscoumacetate; Hematoma; Hemoperitoneum; Humans; Intestinal Obstruction; Jejunum; Male; Middle Aged; Prothrombin; Thrombosis; Vitamin K

Topics: Anticoagulants; Fibrinolytic Agents; Heparin; Humans; Myocardial Infarction; Peptide Hydrolases; Pulmonary Embolism; Streptokinase; Thromboembolism; Thrombophlebitis; Thrombosis; Vitamin K

Topics: Abomasum; Administration, Oral; Animal Feed; Animals; Catheterization; Dicumarol; Diet; Female; Fistula; Male; Medicago sativa; Portal Vein; Prothrombin Time; Rumen; Sheep; Sheep Diseases; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Proteins; Calcium; Dicumarol; Fibrinolysis; Fibrinolytic Agents; Humans; Lipoproteins; Streptokinase; Thrombosis; Vitamin K

Topics: Aneurysm; Animals; Aortic Aneurysm; Aortography; Arteries; Arteriosclerosis; Arteriosclerosis Obliterans; Blood Coagulation; Blood Vessel Prosthesis; Dextrans; Dicumarol; Dogs; Female; Fibrinolytic Agents; Heparin; Humans; Male; Methods; Nylons; Phenindione; Plastics; Postoperative Complications; Suture Techniques; Thrombosis; Vascular Surgical Procedures; Vitamin K

Topics: Blood Coagulation Tests; Coumarins; Heparin; Humans; Massage; Postoperative Complications; Thrombosis; Vascular Resistance; Vitamin K

Topics: Anemia; Angiography; Animals; Cats; Cerebral Hemorrhage; Dogs; Ecchymosis; Embolism; Fever; Gastrointestinal Hemorrhage; Hematoma; Hematuria; Hemorrhage; Hemothorax; Heparin; Humans; Hypotension; Ischemia; Leukocytosis; Shivering; Streptokinase; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation Tests; Surgical Procedures, Operative; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Factor IX; Factor VII; Factor X; Fibrinogen; Hemostasis; Heparin; Humans; Prothrombin; Thrombelastography; Thrombin; Thromboplastin; Thrombosis; Vitamin K

Topics: Acenocoumarol; Blood Coagulation; Blood Coagulation Tests; Dicumarol; Ethyl Biscoumacetate; Humans; Metabolic Clearance Rate; Methods; Prothrombin Time; Spectrum Analysis; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Heparin; Humans; Thrombosis; Vitamin K

Topics: Anticoagulants; Blood Coagulation Tests; Fibrinolytic Agents; Humans; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Thrombosis; Vitamin K

Topics: Anticoagulants; Breast Neoplasms; Dicumarol; Hematuria; Humans; Mastectomy; Neoplasms; Thrombosis; Toxicology; Ureteral Obstruction; Urinary Catheterization; Vitamin K

Topics: Arteriosclerosis; Atrial Fibrillation; Cerebrovascular Disorders; Coronary Disease; Dicumarol; Diet; Diet Therapy; Family Practice; General Practice; Humans; Intracranial Embolism; Intracranial Embolism and Thrombosis; Myocardial Infarction; Prothrombin Time; Thrombosis; Vitamin K; Warfarin

Topics: Antifibrinolytic Agents; Aspirin; Blood; Drug Therapy; Heparin Antagonists; Humans; Naphthoquinones; Pharmacology; Prothrombin Time; Thrombosis; Vitamin K

Topics: Anticoagulants; Fibrinolytic Agents; Humans; Thrombosis; Vitamin K

Topics: Blood Coagulation; Esters; Hemostatics; Heparin Antagonists; Humans; Phosphates; Thrombosis; Vitamin E; Vitamin K; Vitamins

Topics: Accidents; Anticoagulants; Antifibrinolytic Agents; Coumarins; Hemorrhage; Humans; Thrombosis; Vitamin K; Vitamin K 1

Topics: Anticoagulants; Coumarins; Hemostatics; Humans; Phenindione; Protamines; Thrombosis; Vitamin K

Topics: Anticoagulants; Coumarins; Heparin Antagonists; Humans; Infarction; Lung; Myocardial Infarction; Phenprocoumon; Pulmonary Infarction; Thrombosis; Vitamin K

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antifibrinolytic Agents; Hemostasis; Humans; Thrombosis; Vitamin K

Topics: Humans; Thrombosis; Vitamin A; Vitamin E; Vitamin K; Vitamins

Topics: Anticoagulants; Blood Coagulation; Heparin Antagonists; Humans; Thrombosis; Vitamin K; Vitamins