vitamin-k-semiquinone-radical and Antiphospholipid-Syndrome

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

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

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

Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid syndrome (APS). Detection of LA is not via calibrated assays but is based on functional behavior of the antibodies in a medley of coagulation assays. A prolonged clotting time in a screening test is followed by demonstration of phospholipid dependence and inhibitory properties in confirmatory and mixing tests, respectively, which are modifications of the parent screening test. Complications arise because no single screening test is sensitive to every LA, and no test is specific for LA, because they are prone to interference by other causes of elevated clotting times. Several screening tests are available but the pairing of dilute Russell's viper venom time (dRVVT) with LA-sensitive activated partial thromboplastin time (aPTT) is widely used and recommended because it is proven to have good detection rates. Nonetheless, judicious use of other assays can improve diagnostic performance, such as dilute prothrombin time to find LA unreactive with dRVVT and aPTT, and the recently validated Taipan snake venom time with ecarin time confirmatory test that are unaffected by vitamin K antagonist and direct factor Xa inhibitor anticoagulation. Expert body guidelines and their updates have improved harmonization of laboratory practices, although some issues continue to attract debate, such as the place of mixing tests in the medley hierarchy, and areas of data manipulation such as assay cut-offs and ratio generation. This article reviews current practices and challenges in the laboratory detection of LA.

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Factor Xa Inhibitors; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Phospholipids; Prothrombin Time; 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

Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.. We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.. An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.. We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.. Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.. CRD42020216178.

Topics: Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Humans; Rivaroxaban; 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

Anticoagulant treatment is recommended in patients with thrombosis and antiphospholipid syndrome (APS). Conflicting results have been reported on the role of direct oral anticoagulants (DOACs) in these patients. We performed a meta-analysis of randomized controlled trials (RCTs) focused on this issue.. We searched MEDLINE and EMBASE for RCTs comparing DOACs and vitamin K antagonists (VKAs) for secondary thromboprophylaxis in patients with thrombotic APS. The primary objective was to assess the efficacy of DOACs compared to VKAs to prevent recurrence of thromboembolic events. Risk difference (RD) was reported as weighted RD according to Mantel-Haenszel random-effect method.. Three RCTs (426 patients) were included, all comparing rivaroxaban with VKAs. The proportion of recurrences (either arterial or venous) was higher among rivaroxaban patients when compared with those receiving VKAs (9.5% vs 2.8%; RD 6%, 95% CI, -0.05 - 0.18, p=0.29), although non-statistically significant. In patients with an arterial index event, thromboembolic recurrences were more frequent in those treated with rivaroxaban compared to those treated with VKAs (25% vs 6.2%; RD 19%, 95% CI, 0.04 - 0.33; p =0.01; I. The use of rivaroxaban in APS patients is associated with an increased rate of thromboembolic recurrences compared to VKAs, at least in those with arterial index event or triple aPL positivity.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Neoplasm Recurrence, Local; Rivaroxaban; 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

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; Hemoglobinuria, Paroxysmal; Heparin; Humans; Patient Education as Topic; Risk Factors; Thrombocytopenia; Thrombophilia; Vitamin K

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 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

Secondary prevention of venous thromboembolism in antiphospholipid syndrome (APS) is usually made using vitamin K antagonists (VKAs) to maintain an international normalized ratio (INR) between 2.0 and 3.0. The optimal intensity of anticoagulation was determined in two prospective randomized controlled trials, both excluding the benefit of more intense anticoagulation. The same regimen is also recommended in patients with APS and arterial thromboembolism as aspirin does not appear to protect against recurrences. The duration of treatment is usually indefinite because of a substantial risk of recurrence.

Topics: Antiphospholipid Syndrome; Humans; Randomized Controlled Trials as Topic; Secondary Prevention; Venous Thromboembolism; Vitamin K

The optimal course of oral anticoagulant therapy is determined according to the risk of recurrent venous thromboembolism after stopping therapy and the risk of anticoagulant-related bleeding. Clinical risk factors appear to be important in predicting the risk of recurrence whereas the influence of biochemical and morphological tests is uncertain. The risk of recurrent venous thromboembolism is low when the initial episode was provoked by a reversible major risk factor (surgery): 3 months of anticoagulation is sufficient. Conversely, the risk is high when venous thromboembolism was unprovoked or associated with persistent risk factor (cancer): 6 months or more prolonged anticoagulation is necessary. After this first estimation, the duration of anticoagulation may be modulated according to the presence or absence of certain additional risk factors (major thrombophilia, chronic pulmonary hypertension, massive pulmonary embolism): 6 months if pulmonary embolism was provoked and 12 to 24 months if pulmonary embolism was unprovoked. If the risk of anticoagulant-related bleeding is high, the duration of anticoagulation should be shortened (3 months if pulmonary embolism was provoked and 3 to 6 months if it was unprovoked). Lastly, if pulmonary embolism occurred in association with cancer, anticoagulation should be conducted for 6 months or more if the cancer is active or treatment is on going. Despite an increasing knowledge of the risk factors for recurrent venous thromboembolism, a number of issues remain unresolved. Randomised trials comparing different durations of anticoagulation are needed.

Topics: Age Factors; Anticoagulants; Antiphospholipid Syndrome; Cohort Studies; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypertension, Pulmonary; Male; Neoplasms; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Sex Factors; Thrombophilia; Time Factors; Vena Cava Filters; Venous Thrombosis; Vitamin K

Anticoagulation with oral vitamin K antagonists (VKA) is the mainstay of the treatment of venous and/or arterial thromboembolism in patients with antiphospholipid syndrome (APS), although the optimal intensity of anticoagulation remains controversial. The limitations of existing anticoagulants have driven a search for novel agents. Dabigatran etexilate (Pradaxa), a direct thrombin inhibitor (DTI), and rivaroxaban (Xarelto), the first in a new class of drugs, the oral direct factor Xa (FXa) inhibitors, are both fixed-dose orally administered agents. They are now licensed in the UK and Europe for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Prospective randomized clinical trials suggest that these agents, and also apixaban, a further oral direct anti-Xa inhibitor, may have potential in other areas including the treatment of acute VTE, prevention of stroke or systemic embolism in patients with atrial fibrillation (AF) and acute coronary syndromes. Here, we summarize current indications for these agents and address the potential for their use in patients with thrombotic APS.

Topics: Adult; Animals; Anticoagulants; Antiphospholipid Syndrome; Drug Design; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Thromboembolism; Treatment Outcome; Vitamin K

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Education, Medical, Continuing; Female; Humans; Male; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Venous 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

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

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

The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of D-dimer levels may play a role in the assessment of the need for prolonged anticoagulation.. We performed D-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal D-dimer level did not resume anticoagulation, whereas those with an abnormal D-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years.. The D-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P=0.02). Thromboembolism recurred in 24 of 385 patients with a normal D-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal D-dimer level, as compared with those with a normal D-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P=0.02).. Patients with an abnormal D-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal D-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277 [ClinicalTrials.gov].).

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Antiphospholipid Syndrome; Antithrombins; Drug Administration Schedule; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Hemorrhage; Humans; Middle Aged; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Recurrence; Survival Analysis; Ultrasonography; Venous Thrombosis; Vitamin K; Warfarin

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

Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients.. In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB).. APS patients were followed for a median time of 51 (interquartile range 43-63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54-10.28,. During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

Topics: Adult; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Aftercare; Anticoagulants; Antiphospholipid Syndrome; England; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Incidence; Indenes; International Normalized Ratio; Neoplasms; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; State Medicine; Systematic Reviews as Topic; Thrombophilia; Vena Cava Filters; Venous Thromboembolism; Vitamin K

Topics: Antiphospholipid Syndrome; Aspirin; Female; Heparin; Humans; Pregnancy; Pregnancy Complications; Vitamin K

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

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Vitamin K

Topics: Administration, Oral; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Factor Xa Inhibitors; Humans; Lupus Coagulation Inhibitor; Meta-Analysis as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Thromboembolism; Vitamin K; Warfarin

: Vitamin K antagonists (VKA) remain the treatment of choice for catastrophic antiphosphilipid syndrome (CAPS). However, when VKAs do not work for a specific patient, direct oral anticoagulants (DOAC) may be a valid therapeutic alternative. We present a patient with a psychiatric disorder and CAPS who was noncompliant to VKA and low-molecular-weight heparin. He was started on dabigatran and has remained thrombosis-free for 8 years. Due to CAPS he has developed progressive renal failure but dabigatran levels were within the expected range. In conclusion, this case report provides anecdotic evidence that dabigatran may be of use in patients with high-risk APS in whom VKA are not an option.

Topics: Anticoagulants; Antiphospholipid Syndrome; Catastrophic Illness; Dabigatran; Factor Xa Inhibitors; Humans; Male; Treatment Outcome; Vitamin K

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

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

Autoimmune myelofibrosis is a distinct clinicopathological entity that occurs with autoimmune disorders. We report the case of a 44-year-old woman admitted with pancytopenia and clinical features of systemic lupus erythematosus, Sjogren's syndrome and antiphospholipid antibodies syndrome. Bone marrow biopsy showed decreased global cells and an increase of reticulin fibres on argentic coloration, consistent with myelofibrosis. The JAK2 V617, Myeloproliferative leukemia (MPL) and calreticulin mutations were negative. The patient's condition improved after treatment with hydroxychloroquine, vitamin K antagonists and prednisone.

Topics: Adult; Anti-Inflammatory Agents; Antiphospholipid Syndrome; Antirheumatic Agents; Autoimmune Diseases; Diagnosis, Differential; Female; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Pancytopenia; Prednisone; Primary Myelofibrosis; Sjogren's Syndrome; Treatment Outcome; Vitamin K

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

Topics: Anticoagulants; Antiphospholipid Syndrome; Antirheumatic Agents; Drug Therapy, Combination; Endocarditis; Follow-Up Studies; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Vitamin K; Warfarin; Young Adult

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

Multifocal avascular osteonecrosis (AON) is a serious manifestation of systemic lupus erythematosus (SLE). Prothrombotic factors, especially antiphospholipid antibodies (aPL), have been associated with the development of AON; therefore, attenuating the procoagulant state while balancing the haemorrhagic risks might have a rationale when managing this condition. We report a case of a 37-year-old patient with SLE, treated with low doses of corticosteroids and immunosuppressive therapy, who was started on vitamin K antagonist following an episode of deep vein thrombosis while having persistent positivity for aPL. After 2 years, he presented with multifocal AON, involving both femurs and shoulders. The patient underwent a bilateral hip replacement, but despite appropriate anticoagulation therapy after 2 years, he developed another episode of AON at both distal epiphyses of the femurs and proximal epiphyses of the tibias. Multifocal AON should be suspected, especially in the presence of aPL positivity. Its aetiology is still unknown and is most likely multifactorial. Its management is challenging and requires combined approaches.

Topics: Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Diagnosis, Differential; Humans; Lupus Erythematosus, Systemic; Male; Osteonecrosis; Rare Diseases; Treatment Outcome; Venous Thrombosis; 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

Topics: Acenocoumarol; Aged; Antiphospholipid Syndrome; Humans; Lupus Coagulation Inhibitor; Male; Prothrombin Time; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Humans; Thrombolytic Therapy; 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

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Humans; 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

Because of the possible interference of antiphospholipid antibodies (APL) with the phospholipid component of thromboplastin reagents, concerns have been raised about the validity of international normalized ratio (INR) testing to monitor anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome (APS). To investigate the reliability of the INR, we determined the INR using various prothrombin time (PT) assays and compared the results with those of a chromogenic factor X (CFX) assay. The study cohort consisted of 40 APS patients and 100 APL-negative patients who were on anticoagulant therapy for reasons other than APS. The agreement (i.e. the percentage of patients with a difference ≤0.5 INR units) between the PT-derived INR and CFX-derived INR equivalents was only moderate in both patient groups. The best agreement with CFX-derived INR equivalents was observed for the Thromborel S reagent in APS patients (69.1 %) and for Neoplastin Plus in APL-negative patients (72.0 %). Regarding the results for the point-of-care system CoaguChek XS, an agreement between the INR and the CFX-derived INR equivalent was less frequently observed in the APS patients (55.6 vs. 67.8 %; p = 0.050). When considering all 3058 pairs of INR tests within the international sensitivity index (ISI)-calibrated range of 1.5 to 4.5 s, we did not observe a higher variability of INR values in either the APS patient group or the subgroup of APS patients positive for lupus coagulants compared with the APL-negative controls. In conclusion, monitoring vitamin K antagonists (VKA) therapy with laboratory INR measurements seems to be suitable for the majority of APS patients.

Topics: Adult; Aged; Animals; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Cohort Studies; Drug Monitoring; Female; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time; Rabbits; Vitamin K

Topics: Adolescent; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Vitamin K; Young Adult

According to the ISTH guidelines for lupus anticoagulant (LAC) testing, the second step in the three-step procedure (screening, mixing, and confirmation) is the mixing test, which improves the discrimination between the presence of an inhibitor and coagulation factor deficiencies such as those occurring in patients receiving vitamin K antagonists (VKAs).. From a retrospective analysis of dilute Russell viper venom (dRVVT) results, we evaluated the impact of the mixing test result on the interpretation of LAC positivity.. We interpreted the dRVVT clotting times with and without taking into account the results of the mixing test in a patient population with prolonged screening test (n = 267) with special attention to the patients receiving VKAs.. The number of samples classified as 'LAC positive' differed substantially depending on the method of interpretation; 170 and 235 of 267 samples were classified as LAC positive with the three- and two-step procedure, respectively. Discrepancy between the two-step (without mixing step) and the three-step procedure was due to not including a mixing test and was more pronounced in the VKA patient population. Screen/confirm ratios carried out on a 1:1 mix of patient and normal pooled plasma (NPP) gave a lower incidence of 59 of 267. We advise continuing to perform mixing test to avoid false-positives. In patients with discrepant results between the two- and three-step dRVVT interpretation, mainly observed in VKA-treated patients, we advise retesting of the patients preferable beyond the period of anticoagulant therapy and additional testing for anti-beta2GPI and/or anti-cardiolipin antibodies.

Topics: Anticoagulants; Antiphospholipid Syndrome; Biomarkers; Blood Coagulation; Humans; Lupus Coagulation Inhibitor; Predictive Value of Tests; Prothrombin Time; Reproducibility of Results; Retrospective Studies; Vitamin K

The dRVVT test for detecting lupus anticoagulants (LA) is difficult to interpret when patients are treated with vitamin K antagonists (VKA).. We performed LA testing in 33 VKA-treated patients with definite antiphospholipid syndrome (APS) and compared the results with 100 controls subjects not receiving VKA and 110 APL-negative patients anticoagulated for reasons other than APS.. Compared with the dRVVT ratio before the initiation of VKA therapy, a higher cutoff value, defined as the 99th percentile, was established for VKA-treated patients with INR values between 2.0 and 3.5. A dRVVT ratio of >1.7 yielded a sensitivity of 81.3%, specificity of 99.1%, and positive and negative predictive values of 98.7% and 85.8%, respectively, for detecting LA. Cohen's kappa coefficient indicated good agreement for the dRVVT ratio obtained from testing with and without VKA treatment (κ = 0.813; 95% CI: 0.773-0.853), which was higher (κ = 0.941; 95% CI: 0.917-0.965) when the LA diagnosis was based on the results of both the dRVVT and a second test system (i.e., Mixcon-LA assay).. Lupus anticoagulants testing in VKA-treated patients with APS according to current guidelines appears to be possible for the majority of patients without discontinuing anticoagulant therapy.

Topics: Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Vitamin K; Young Adult

Coagulation factor deficiencies are thought to interfere with the detection of the phospholipid-dependent coagulation inhibitor known as lupus anticoagulant (LA). Treatment with vitamin K antagonists (VKA) in particular, is thought to preclude accurate LA assessment. For this reason, the procedure to detect LA includes a mixing test, in which coagulation factor deficiencies are corrected by mixing samples with an equal volume of normal plasma. Despite these mixing tests, interpretation of LA test results is considered difficult in patients receiving high intensity VKA treatment. As a result, VKA treatment is often temporarily discontinued to allow LA assessment. However, whether coagulation factor deficiencies influence LA test results is unclear. We found that neither deficiency of a single coagulation factor, nor a functional coagulation factor deficiency due to high intensity VKA treatment, resulted in false positive dRVVT- or APTT-based (silica clotting time; SCT) LA test results. LA was readily detected in unmixed samples from VKA-treated LA-positive patients with both dRVVT and SCT reagents. VKA treatment caused an underestimation of the strength of the LA with SCT reagents, but did not lead to misclassification of LA status. Although mixing with normal plasma during both screen and confirm tests allowed more accurate assessment of the strength of the LA with SCT reagents in samples with an international normalised >2.5, the mixing procedure itself lead to misclassification of LA in weakly positive samples from patients not treated with VKA. Based on these findings, we conclude that mixing studies are not necessary during LA-assessment.

Topics: Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Clinical Laboratory Techniques; False Positive Reactions; Female; Humans; International Normalized Ratio; Lupus Coagulation Inhibitor; Pregnancy; 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

There are several issues regarding diet in patients with antiphospholipid syndrome. This article focuses on main factors such as vitamin K ingestion and its relationship with anticoagulants and healthy diet for obesity, dyslipidemia, hypertension, diabetes mellitus that are important risk factors for hypercoagulability. Last, diet rich in calcium is also important since these patients are under anticoagulants and heparins that are related to osteoporosis/osteopenia. The medical follow-up in combination with nutrition counseling was carried out for guiding patients to acquire healthy habits in order to improve their quality of life and gain control of the comorbidities.

Topics: Antiphospholipid Syndrome; Counseling; Diet; Humans; International Normalized Ratio; Vitamin K

Topics: Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Female; Humans; Male; Middle Aged; Point-of-Care Systems; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Vitamin K

Antiphospholipid syndrome associate thromboembolic events (arterial or venous), and presence of antiphospholipid antibodies, and require anticoagulation. A catastrophic variant may develop, resulting in multiorgan failure, with high mortality rate. This article presented a patient with antiphospholipid syndrome presenting a catastrophic antiphospholipide syndrome after anticoagulation suspending for gastrointestinal bleeding. Multidisciplinary management in intensive care unit and aggressive therapies (corticosteroids, anticoagulation, plasma exchange) were essential to rescue the patient.

Topics: Anemia; Anticoagulants; Antiphospholipid Syndrome; Biopsy; Catastrophic Illness; Gastrointestinal Hemorrhage; Hemoglobins; Hemostatics; Heparin; Humans; Male; Middle Aged; Platelet Count; Respiratory Insufficiency; Vitamin K

Topics: Abnormalities, Drug-Induced; Anticoagulants; Antiphospholipid Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Infant, Newborn; Infant, Premature, Diseases; Maxillofacial Abnormalities; Phenprocoumon; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Ultrasonography, Prenatal; Vitamin K

One of the conclusions of the subcommittee meeting on Lupus Anticoagulant/Phospholipid dependent antibodies, held in Geneva on 2007, was the need to update the guidelines on Lupus Anticoagulant (LA) detection. Particular emphasis was given to several aspects discussed in this official communication. A new paragraph is dedicated to the patient selection, and aims to minimize inappropriate requests for LA testing. Modalities for blood collection and processing are fully delineated and the choice of tests is limited to dRVVT and a sensitive aPTT. Calculation of cut-off values for each diagnostic step are clearly stated. A final paragraph reports the interpretation of the results in general and in particular situations.

Topics: Anticoagulants; Antiphospholipid Syndrome; Artifacts; Blood Coagulation; Blood Specimen Collection; Female; Humans; Indicators and Reagents; Lupus Coagulation Inhibitor; Male; Partial Thromboplastin Time; Patient Selection; Phospholipids; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Specimen Handling; Vitamin K

Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Dose-Response Relationship, Drug; Humans; International Normalized Ratio; Platelet Aggregation Inhibitors; Prothrombin Time; Thrombophilia; Vitamin K; Warfarin

The antiphospholipid syndrome had been rarely reported as a cause of mesenteric venous thrombosis.. We report two exceptional cases of primary antiphospholipid syndrome associated with mesenteric venous thrombosis in 51 years old man and 27 years old women.. Identifying the underlying process is very important to try to propose a specific treatment.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Middle Aged; Time Factors; Treatment Outcome; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Clinical Trials as Topic; Female; Hemorrhage; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Pregnancy; Recurrence; Retrospective Studies; Risk; Vitamin K; Warfarin

We report the first case of acute acalculous cholecystitis associated with primary antiphospholipid-antibody syndrome. The diagnosis was serological and was based on positive tests for lupus anticoagulant or anticardiolipin antibodies. The treatment was exclusively medical. Cholecystitis was cured with low-molecular weight heparin and oral anticoagulants. A rapid diagnosis can prevent lack of therapeutic errors such as surgery, antibiotherapy or corticotherapy, and long-term anticoagulant treatment can be proposed to prevent recurrent thrombosis.

Topics: Acute Disease; Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Cholecystitis; Female; Heparin, Low-Molecular-Weight; Humans; Ultrasonography; Vitamin K

We analyzed the clinical and biological characteristics as well as the clinical course and outcome observed in 20 patients with antiphospholipid antibodies and clinical signs including thrombosis or repeated spontaneous abortion to better identify the recently described antiphospholipid syndrome.. We retrospectively studied all patients observed in our unit from 1981 to 1992 who fulfilled the following inclusion criteria: a) at least one episode of arterial or venous thrombosis and/or repeated spontaneous abortions, b) positive for antiphospholipid antibodies.. Twenty patients were included, 3 with systemic lupus erythematosus (according to the American Rheumatism Association criteria). Arterial or venous thrombosis occurred in 9 and 16 respectively, including exceptional cases of cerebral phlebitis and thrombosis of dermal capillaries. High blood pressure was recorded in 8. Only 1 or 2 types of antiphospholipid antibodies were found in most patients. Anticardiolipin, a circulating anticoagulant and a false-positive Bordet-Wassermann reaction were found together in only 3 out of 16. In addition, the antibody level varied independently from the thrombotic events. There was no case with a clinical course from primary antiphospholipid syndrome to systemic erythromatosus lupus. The effect to treatment on occurrence of new thrombotic events was studied. Three patients suffered one or more haemorrhagic events during antivitamin K treatment.. It is difficult to establish a differentiation between primary antiphospholipid syndrome, systemic lupus erythematosus and lupus-like syndromes, and precise methods of identifying antiphospholipid antibodies should be further developed.

Topics: 4-Hydroxycoumarins; Adrenal Cortex Hormones; Adult; Anticoagulants; Antiphospholipid Syndrome; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indenes; Intracranial Embolism and Thrombosis; Male; Middle Aged; Pregnancy; Pulmonary Embolism; Retrospective Studies; Thrombophlebitis; Vitamin K