acenocoumarol and Venous-Thrombosis

Deep vein thrombosis (DVT) has an incidence of 1 case per 1000 inhabitants in the general population and it is very rare after arthroscopy of the shoulder. Therefore, the current guidelines do not advise the administration of DVT prophylaxis in shoulder arthroscopy procedures.. We describe two cases of thrombosis of the arm after shoulder arthroscopy on a total of 10.452 shoulder arthroscopies performed during a period of ten years. One of two patients was further complicated by a bilateral pulmonary microembolism. In these two clinical cases the complication developed despite the absence of risk factors such as a concomitant neoplasm, thrombophilia, smoking habit, or a long duration of the procedure.. The DVT after shoulder arthroscopy procedure remain a very rare complication. However, in view of the growing number of patients undergoing this procedure, this figure is expected to rise. The clinician surgeon should take in mind this possible complication that normally appears in the first 3 weeks after surgery, so to perform anti-coagulant treatment. Further clinical studies are therefore warranted to assess the true risk of VTE. In fact, the presence of "minor" predisposing factors that are not routinely studied, as well as the postoperative immobilization period, are potential risk factors that, associated with the invasiveness of the arthroscopy procedure, could trigger a thromboembolism.

Topics: Acenocoumarol; Anticoagulants; Arm; Arthroscopy; Axillary Vein; Dyspnea; Edema; Heparin, Low-Molecular-Weight; Humans; Hyperbaric Oxygenation; Male; Middle Aged; Perfusion Imaging; Postoperative Care; Postoperative Complications; Pulmonary Embolism; Risk Factors; Shoulder Joint; Thrombophilia; Ultrasonography, Doppler, Color; Venous Thrombosis; Young Adult

Currently, pharmacological thromboprophylaxis is frequently required in patients undergoing surgery, due to the high risk of deep venous thrombosis in the perioperative period. The administration of these anticoagulant agents (in Spain, usually low molecular weight heparins or fondaparinux, and in future, probably also the new oral anticoagulants dabigatran and rivaroxaban) may conflict with regional anesthetic techniques, in which maintaining hemostatic integrity is essential. Therefore, safety protocols have been designed that allow thromboprophylaxis to be administered with optimal effectiveness and anesthetic techniques to be performed with maximal safety; these protocols are based on the drug used, as well as on the dose and time of administration. The present chapter reviews the details related to these issues.

Topics: Acenocoumarol; Administration, Oral; Anesthesia, Conduction; Anticoagulants; Benzimidazoles; Clinical Protocols; Dabigatran; Early Ambulation; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Risk Factors; Rivaroxaban; Safety; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Venous Thrombosis

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atorvastatin; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; International Normalized Ratio; Male; Patient Compliance; Pyrroles; Simvastatin; Venous Thrombosis; Warfarin

The evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban.. The study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events.. A total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group - two DVTs and one ischemic stroke - and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008-2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005-1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group.. In this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.

Topics: Acenocoumarol; Anticoagulants; Aspirin; Hemorrhage; Humans; Ischemic Stroke; Pilot Projects; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping.. Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. Objectives To explore possible reasons for the lack of differences between trial arms by performing a secondary analysis of EU-PACT data in order to evaluate the performance of both dosing algorithms across VKORC1-CYP2C9 genetic subgroups. Patients/Methods Anticoagulation control measured according to an International Normalized Ratio (INR) below (INR of < 2), within (INR of 2-3) and above (INR of > 3) the therapeutic range was compared across VKORC1-CYP2C9 subgroups. Owing to a low number of patients in each subgroup, trials for acenocoumarol and phenprocoumon were combined for analysis. Results Four weeks after therapy initiation, genotype-guided dosing increased the mean percentage of time in the therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9*1*1 subgroup as compared with the non-genetic dosing (difference of 14.68%, 95% confidence interval [CI] 5.38-23.98). For the VKORC1 AA-CYP2C9*1*1 subgroup, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (difference of 19.9%; 95% CI 11.6-28.2). Twelve weeks after therapy initiation, no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic subgroups. Conclusions EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose overcautiously in the VKORC1 AA-CYP2C9*1*1 subgroup. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping.

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Data Interpretation, Statistical; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Phenprocoumon; Prospective Studies; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

We performed a subanalysis of cancer patients enrolled in a clinical trial that compared long-term (6 months) treatment with a low-molecular-weight heparin (LMWH) administered subcutaneously or with acenocoumarol. The subanalysis assessed whether the characteristics of the tumor had an influence on the clinical response. A randomized open trial included 69 patients with cancer and symptomatic proximal deep vein thrombosis of the lower limbs. The tumor characteristics and treatment type were recorded. The main assessment criterion was the 12-month incidence of recurrent symptomatic venous thromboembolism (VTE). Sixty-one patients (88.4%) were analyzed. At the time of inclusion, the cancer characteristics and treatment were comparable between the 2 groups. Over the course of 12 months, the recurrent VTE was significantly greater in the elderly patients (71.5 ± 6.4 vs. 62.0 ± 15.1; p=.006). The logistic regression analysis showed no association between VTE recurrence and the location or extent of the tumor. However, the use of thrombogenic chemotherapy (p=.045) was independently associated with VTE recurrence, and longterm treatment with tinzaparin was almost a protective factor (p=.15). In this small sample, we observed an association between thrombogenic chemotherapy and recurrent VTE. The tendency towards a reduction in VTE recurrence at 12 months in patients with cancer in the LMWH group could be attributed to the effect of the full LMWH dosage.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Logistic Models; Male; Middle Aged; Neoplasms; Recurrence; Risk Factors; Treatment Outcome; Venous Thrombosis

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Hemorrhage; Humans; Lower Extremity; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.. We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.. The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).. Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Topics: Acenocoumarol; Acute Disease; Administration, Oral; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).. A randomised, open-label trial.. In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.. During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.. Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.

Topics: Acenocoumarol; Administration, Oral; Age Factors; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Middle Aged; Neoplasms; Prospective Studies; Recurrence; Risk Factors; Tinzaparin; Ultrasonography, Doppler, Duplex; Venous Thrombosis

To meet growing demand for oral anticoagulation worldwide there has been increased dependence on computer-assistance in dosage although the safety and effectiveness of any of the individual computer-assisted dosage programs has not previously been established. This randomised multicentre clinical end-point study assessed a new version of the PARMA 5 program. It compared PARMA 5 safety and effectiveness with manual dosage by experienced medical staff at 19 centres with a known interest in oral anticoagulation. Target recruitment was 8000 patient-years, randomised to medical staff or PARMA-5 assisted dosage. Safety and effectiveness of the PARMA 5 program was compared with manual dosage. A total of 10,421 patients were recruited (15,369 patient-years) in the 5-year study. International normalised ratio (INR) tests numbered 167,791 with manual and 160,078 with PARMA 5 dosage. With parma 5 there was overall a non-significant reduction in clinical events but in the 2542 patients with deep vein thrombosis/pulmonary embolism, clinical events were significantly reduced (P = 0.005). Success in achieving 'time in target INR range' was also significantly greater with PARMA 5 compared with the dosage by experienced medical staff. This study demonstrated the safety and effectiveness of PARMA 5-assisted dosage.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Drug Therapy, Computer-Assisted; Female; Follow-Up Studies; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Pulmonary Embolism; Software; Software Design; Treatment Outcome; Venous Thrombosis; Warfarin

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Enoxaparin; Female; Hemorrhage; Humans; In Vitro Techniques; Length of Stay; Middle Aged; Pulmonary Embolism; Secondary Prevention; Venous Thrombosis

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Drug Administration Schedule; Humans; Middle Aged; Outpatients; Pulmonary Embolism; Rural Population; Treatment Outcome; Venous Thrombosis

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

Evaluation of the effectiveness and safety of the low molecular weight heparin (LMWH) tinzaparin versus unfractionated heparin (UFH) followed by acenocoumarol in proximal deep venous thrombosis (DVT).. Prospective, randomized clinical trial.. Consecutive patients (n=108) with acute leg DVT, confirmed by duplex, were randomized to either tinzaparin alone or UFH and acenocoumarol for 6 months. Patients were evaluated ultrasonographically at entry, 1, 3, 6 and 12 months. Thrombus regression, reflux distribution and the incidence of complications were studied. A cost-analysis, comparing the two treatments, was performed.. The overall incidence of major events (mortality, DVT recurrence, pulmonary embolism, major bleeding, heparin-induced thrombocytopenia) was significantly different (p=0.035) in favor of tinzaparin (7 versus 17 events). The ultrasonographic clot volume score (an index of recanalization) decreased significantly in both treatment groups. However, tinzaparin produced significantly more extended overall recanalization from 3 months onwards (p<0.02). Thrombus regression was equivalent or in favor of tinzaparin in the different DVT subgroups and venous segments, but the statistical significance varied. Reflux showed non-significant differences overall or in subgroups. A cost-analysis resulted in favor of LMWH.. A fixed daily dose of tinzaparin for 6 months was at least as effective and safe as UFH and acenocoumarol. Regarding major events and recanalization, there was a significant benefit in favor of tinzaparin. Long-term DVT treatment with tinzaparin could represent an alternative to conventional treatment.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Injections, Subcutaneous; Long-Term Care; Male; Middle Aged; Partial Thromboplastin Time; Pulmonary Embolism; Recurrence; Tinzaparin; Ultrasonography, Doppler, Duplex; Vascular Patency; Venous Thrombosis

Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).. During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Dalteparin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Secondary Prevention; Survival Analysis; Thromboembolism; Venous Thrombosis; Warfarin

Oral anticoagulant therapy is initiated in most hospitals in The Netherlands by clinicians who routinely dose oral anticoagulants (without using an algorithm). This may explain the low proportion of patients leaving the hospital stabilized. To test this hypothesis this study compared the dosing of acenocoumarol in orthopedic and surgical patients using an algorithm with routine dosing. Because of the routine administration of low molecular weight heparin for at least the first 5 days of acenocoumarol therapy, the study focused on supratherapeutic INR-values during this period. The study included 103 patients and was performed on orthopedic surgery and general surgery wards of a Dutch hospital over 5 months. The patients received acenocoumarol as an oral anticoagulant to prevent venous thromboembolism after general of orthopedic surgery. Patients were randomized into a group routinely dosed by physicians (n=54) and a group dosed using a dosing algorithm (n=49). A patient was defined as stable if he had two consecutive INR values within the range of 2-3 during hospitalization with the first (of the two consecutive INR values within range) having been measured on day 5 or later. The groups did not differ significantly in proportion of patients stabilized, time to stabilization, or length of hospitalization. In the first period (days 1-5) the routine dosing group had significantly more INR values above therapeutic range than the algorithm group, while the algorithm group had more INR values below the therapeutic range. There were two bleeding episodes in the routine dosing group and none in the algorithm group. Despite the lack of differences in stabilization between the two groups, this study suggests an advantage of dosing acenocoumarol using an algorithm in a study population consisting of prophylactically treated, mostly elderly orthopedic patients. The algorithm provides a safe dosing schedule for elderly postoperative patients who use low molecular weight heparin and NSAIDs concomitantly and are thus at high risk for bleeding complications.

Topics: Acenocoumarol; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Comorbidity; Female; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Postoperative Complications; Venous Thrombosis

Oral anticoagulants and low-molecular-weight heparin are both recommended for venous thromboembolism prophylaxis after total hip replacement. To date, these regimens have not been compared by means of clinical end points in the extended prophylaxis setting.. We randomly assigned 1279 patients 3 days after total hip replacement surgery to fixed-dose subcutaneous low-molecular-weight heparin (reviparin sodium, 4200 anti-Xa IU) or adjusted-dose oral anticoagulant (international normalized ratio, 2-3; acenocoumarol) for a 6-week period. The primary end point was the failure rate, defined as the combined clinical events of a confirmed symptomatic thromboembolic event, a major hemorrhage, or death. All patients were followed up throughout the study interval. The primary objective was to compare the observed cumulative failure rate in the low-molecular-weight heparin vs oral anticoagulant group.. In the intent-to-treat population, objectively documented symptomatic thromboembolic events occurred in 15 (2.3%) of 643 patients vs 21 (3.3%) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants, respectively (P =.30; 95% confidence interval for the difference, -0.8% to 2.8%). Major bleeding occurred in 9 (1.4%) of 643 patients vs 35 (5.5%) of 636 patients receiving low-molecular-weight heparin or oral anticoagulants, respectively (P =.001). The failure rate was 24 (3.7%) of 643 patients compared with 53 (8.3%) of 636 patients who received low-molecular-weight heparin or oral anticoagulants (P =.001).. A significantly higher benefit-risk ratio was observed for patients undergoing elective hip replacement who received extended out-of-hospital prophylaxis with low-molecular-weight heparin vs acenocoumarol. Low-molecular-weight heparin prophylaxis was at least as effective as oral anticoagulants, but with a marked improvement in safety.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Thromboembolism; Venous Thrombosis

In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial.. Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy (with warfarin, in 97 percent of the cases and acenocoumarol in 3 percent) were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up.. The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of 0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine months after randomization (after all patients received three months of therapy), 1 patient had a recurrence while receiving oral anticoagulant therapy (0.7 percent), as compared with 11 of the patients assigned to the discontinuation of oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence after the discontinuation of treatment was 5.1 percent per patient-year in patients in whom oral anticoagulant therapy was discontinued after 3 months (95 percent confidence interval, 3.2 to 7.5 percent; average interval since discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who received an additional 9 months of oral anticoagulant therapy (95 percent confidence interval, 3.1 to 7.8 percent; average interval since discontinuation, 29.4 months). None of the recurrences were fatal. Four patients had non-fatal major bleeding during the extended period of anticoagulant therapy (3.0 percent).. In patients with idiopathic deep venous thrombosis, the clinical benefit associated with extending the duration of anticoagulant therapy to one year is not maintained after the therapy is discontinued.

Topics: Acenocoumarol; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Humans; International Normalized Ratio; Middle Aged; Recurrence; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

It is yet unclear whether vitamin K antagonist treatment should be stopped abruptly or gradually after an episode of venous thromboembolism. The mode of withdrawal might influence a potential development of a hypercoagulable state, which could influence the risk for recurrent disease.. We prospectively studied 37 consecutive patients in whom acenocoumarol was discontinued either abrupt (18) or gradually (19) (2/3 and 1/3 of the initial dose for one week). Blood sampling was performed at various time points up to 18 days after complete withdrawal and was analysed for INR, prothrombin fragment F1 + 2 and D-dimer. All patients were clinically followed-up for the assessment of the association between hypercoagulability and occurrence of disease such as recurrent venous thromboembolism or malignancy.. An approximately fourfold increase was observed (median increase from 0.3 to 1.3 nmol/l) in the F1 + 2 levels after both abrupt and gradual withdrawal and in the D-dimer concentrations in the abrupt withdrawal group (0.10 to 0.44 mg/l), while those in whom acenocoumarol was discontinued gradually showed a less pronounced increase of the D-dimer levels (0.11 to 0.29 mg/L) (not significant). During follow-up one recurrent venous thromboembolic event occurred in each group, and a diagnosis of cancer was made four times. All these patients had the highest D-dimer concentrations measured in the entire study group.. This study indicates the potential for a hypercoagulable state after acenocoumarol discontinuation, which was not prevented by tapering the acenocoumarol dose. D-dimer, measured 2 to 3 weeks after acenocoumarol withdrawal, might be an important tool to identify patients at risk for recurrent venous thromboembolism and/or for the presence of an underlying malignancy.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice daily doses. When the drug effect had been at a steady-state for at least 72 h, five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups (P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain. In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice-daily administration of acenocoumarol does not appear to be justified.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Female; Humans; Male; Middle Aged; Time Factors; Venous Thrombosis

Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA.. This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded.. Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09).. Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.

Topics: Acenocoumarol; Adult; Anticoagulants; Budd-Chiari Syndrome; Duration of Therapy; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Mesenteric Ischemia; Middle Aged; Portal Vein; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thrombosis; Warfarin

Ischemic stroke is a complex multifactorial disorder. Anticoagulation is a growing research area, with the main goal of preventing systemic embolization and stroke. We report the case of a 41-year-old woman with antiphospholipid syndrome who was unsuccessfully treated with Dabigatran, a new oral anticoagulant, as she developed a major stroke involving the right carotid artery, due to deep venous thrombosis with pulmonary embolism. We therefore suggest a closer monitoring of the safety and efficacy of dabigatran. Moreover, in the presence of multifactorial causes of pro-coagulation, we believe that warfarin should remain the mainstay of oral anticoagulation.

Topics: Abortion, Spontaneous; Acenocoumarol; Adult; Antiphospholipid Syndrome; Antithrombins; Carotid Arteries; Computed Tomography Angiography; Dabigatran; Female; Follow-Up Studies; Humans; Product Surveillance, Postmarketing; Pulmonary Embolism; Stroke; Treatment Outcome; Venous Thrombosis; Warfarin

Paget-Schroetter syndrome (PSS), or effort thrombosis, refers to axillary and/or subclavian vein thrombosis associated with repetitive effort of the superior limbs, and is rare in the pediatric population. We report the case of a previously healthy 15-year-old boy who presented with a painful and swollen right arm after throwing firecrackers. Doppler ultrasound showed extensive right subclavian and axillary vein thrombosis. Anticoagulation therapy was started and had favorable evolution. We emphasize that PSS must be included in the differential diagnosis of a swollen arm.

Topics: Acenocoumarol; Adolescent; Anticoagulants; Enoxaparin; Humans; Male; Subclavian Vein; Thrombolytic Therapy; Treatment Outcome; Ultrasonography, Doppler; Upper Extremity Deep Vein Thrombosis; Venous Thrombosis

The non-vitamin K antagonist oral anticoagulant rivaroxaban is indicated in prevention and treatment of venous thromboembolism (VTE). A 60-year-old male patient complained of bilateral ptosis after administration of rivaroxaban for deep vein thrombosis (DVT). Myasthenia gravis (MG) was confirmed by positive serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found. The ocular myasthenia reversed after discontinuing rivaroxaban treatment. Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment was necessary. The mechanism of MG development by rivaroxaban therapy is not completely understood. The development of rivaroxaban-induced autoimmune disease could be based on cross-reactivity between antibodies against rivaroxaban-derived antigens or by T-cell activation. To our knowledge, this report of ocular myasthenia by rivaroxaban administration is the first in the literature. Despite the benefits of rivaroxaban, it is important to recognize unexpected immune-related adverse events.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Autoantibodies; Biomarkers; Blepharoptosis; Cholinesterase Inhibitors; Drug Substitution; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myasthenia Gravis; Oculomotor Muscles; Pyridostigmine Bromide; Receptors, Cholinergic; Rivaroxaban; Treatment Outcome; Venous Thrombosis

We aimed to study potential variables involved in interindividual variability to acenocoumarol (AC) response in order to establish a pharmacogenetic algorithm (PA) that includes clinical and genetic factors to predict adequate AC dose to stabilize anticoagulation in a cohort of Tunisian patients.. Genotyping of the CYP2C9, VKORC1, CYP4F2, and CALU polymorphisms was conducted on 246 patients using PCR-RFLP technique. AC normalized maintenance dose (NMD): ((mean maintenance dose/international normalized ratio (INR)) equilibrium) was calculated. The statistical study was carried out with SPSS V20.. A significant correlation was found between age, BMI, and daily AC dose (r = - 0.397; p < 0.001 and r = 0.215; p = 0.001, respectively). The carriers of mutated alleles CYP2C9*2 or CYP2C9*3 or VKORC1 haplotypes (H1 and H7) were associated with AC hyper-sensibility. After adjustment to potential covariates, these patients presented supra-therapeutic INR during treatment period and needed low AC dose (ORs* = 0.28 [0.06-0.60], p = 0.004; ORs* = 0.12 [0.04-0.05], p < 0.001; ORs* = 0.45 [0.24-0.84], p = 0.01; and ORs* = 0.28 [0.06-0.98], p = 0.049, respectively). However, carriers of VKORC1 haplotypes (H3 and H12) or mutated alleles CYP4F2 (rs2108622) or CALU (rs1043550) tend to resist to treatment, hence long period of therapy initiation, and must be treated with high AC dose (ORs* = 2.67 [81.12-5.91], p = 0.013; ORs* = 8.76 [1.07-76.26], p = 0.019; ORs* = 3.12 [1.01-9.63], p = 0.047; and ORs* = 3.96 [1.41-11.09], p = 0.009, respectively). A final multivariate regression model explained 48.1% of the global interindividual variability in AC dose requirement.. The PA demonstrated that VKORC1 and CYP2C9 polymorphisms contribution was more important than clinical factors. Applying the PA would allow dose adjustment to treat patients in a personalized manner.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Black People; Calcium-Binding Proteins; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 4; Female; Genotype; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Single Nucleotide; Tunisia; Venous Thrombosis; Vitamin K Epoxide Reductases; Young Adult

Subcutaneous unfractionated heparin (SCUFH) has been proved effective in puerperal cerebral venous thrombosis (CVT), but its efficacy in the more serious form of the disease such as deep CVT patients (DCVT) unreported. We describe the outcomes of 37 (isolated:combined: 11:26) patients of DCVT diagnosed by MRI, treated with SCUFH in a tertiary care stroke unit. It was a prospective observational cohort study using 5000 U of SCUFH every 6 hourly for 10 days with oral Acenocoumarol started on day 7, with monitoring. The outcome was assessed by modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS) and Barthel's activities of daily life (BADL) at 3 months. The mean age of the cohort was 27.9 ± 9.7 years, females (n = 24) outnumbering the males (n = 13). Mean duration of symptoms being 10.2 ± 15.9 days. MRI showed vein of Galen and straight sinus involvement in 36 (97.3%) patients, with sparing of the basal vein of Rosenthal in 28 (75%). Thalamus 27 (73%) basal ganglia 21 (56.7%) were commonly involved areas with hemorrhagic lesions in 18 (48.6%) patients. The median NIHSS score at presentation was 11 (1-21). Mean duration of SCUFH treatment was 9.3 ± 1.3 days and the mean aPTT on day 7 was 49.3 ± 9.8 s (control 32-39 s), mean PT INR on day 13 was 1.5 ± 0.45. All the patients improved with no mortality in the study group. At 3 months, good functional outcome (mRS: 0-2) was observed in 94.6% (n = 35) of patients. Two patients had mRS-3. The median mRS (3{1-5} to 0{0-3}) and BADL (8{0-20} to 20{8-20}) improved at 3 months. Complications seen were thrombocytopenia-1, infection-6 and deep vein thrombosis of leg-4. Our preliminary data suggests that SCUFH is safe, effective treatment option in patients with DCVT in a stroke unit with minimal monitoring.

Topics: Acenocoumarol; Adolescent; Adult; Cohort Studies; Drug Monitoring; Female; Heparin; Humans; Injections, Subcutaneous; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Partial Thromboplastin Time; Prospective Studies; Treatment Outcome; Venous Thrombosis; Young Adult

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Calciphylaxis; Humans; Kidney Failure, Chronic; Male; Venous Thrombosis

There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients.. Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted.. The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years.. It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Female; Humans; India; International Normalized Ratio; Male; Middle Aged; Pregnancy; Stroke; Tertiary Care Centers; Venous Thrombosis

Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Phenprocoumon; Prognosis; Risk Factors; Venous Thrombosis; Vitamin K

The study aimed at evaluating the contribution of genetic variations in the drug metabolizing enzyme, CYP2C9, and the influence of co-medication with the antiepileptic drug, phenytoin, to variability in acenocoumarol response, in patients with cerebral venous thrombosis (CVT).. 476 acenocoumarol-treated CVT patients (153 males and 323 females) were genotyped for CYP2C9*2 and CYP2C9*3 polymorphisms by PCR-RFLP method. Mean acenocoumarol dose required for achieving and maintaining a stable international normalized ratio (INR) was calculated for different genotypes. The effect of co-administration with phenytoin was determined.. Genotype distributions of CYP2C9 were as follows: 83%CYP2C9*1/*1, 8.6%CYP2C9*1/*3, 5.9%CYP2C9*1/*2, 1.9%CYP2C9*3/*3, 0.4%CYP2C9*2/*3 and 0.2%CYP2C9*2/*2. During the initiation phase of anticoagulation the CYP2C9*2 allele was independently associated with low acenocoumarol dose requirement (Adjusted OR 5.38; 95%CI 1.65-17.49; p=0.005). Similarly, the adjusted odds ratio for requiring a low dose during the induction phase in patients bearing the CYP2C9*3 allele was 12.79 (95%CI 4.74-34.57; p<0.0001). During the maintenance phase, CYP2C9*2 and CYP2C9*3 alleles were associated with 19-fold (Adjusted OR 19.67; 95%CI 2.46-157.19; p=0.005) and 11.9-fold odds (Adjusted OR 11.98; 95%CI 2.61-55.08; p=0.001) of requiring a low dose. Clinical covariates such as age, alcohol consumption, postpartum state and oral contraceptive intake also influenced acenocoumarol dosage. Co-medication with phenytoin was associated with lower dose requirement across genotypes during the initiation phase. However, during the maintenance phase, phenytoin-treated patients of all genotypes required higher doses of acenocoumarol.. This study emphasizes the fact that polymorphisms in CYP2C9 gene and co-medication with phenytoin alter the anticoagulant effect of acenocoumarol.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Cytochrome P-450 CYP2C9; Drug Interactions; Female; Genotype; Humans; Intracranial Thrombosis; Male; Middle Aged; Phenytoin; Polymorphism, Genetic; Prevalence; Venous Thrombosis; Young Adult

Lenalidomide has significant antimyeloma activity but it is associated with a significant risk of venous thromboembolism (VTE). In this study, we assessed clinical and genetic risk factors that may predispose for VTE in myeloma patients who were treated with lenalidomide-based regimens. We analyzed common clinical and selected genetic factors in 200 consecutive, unselected myeloma patients who were treated with lenalidomide-based regimens in a single institution. Twelve patients (6%) developed a VTE (nine deep venous thrombosis and three pulmonary embolism). All VTEs occurred in patients who were receiving aspirin prophylaxis; no patient who received LMWH or acenocoumarol had a VTE. The frequency of VTEs was 9.4% in previously untreated and 4.5% in previously treated patients. VTEs were more frequent in patients >65 years (8.1% vs. 1.6%) especially among patients receiving aspirin as prophylaxis (10.4% vs. 1.8% for patients ≤65 years). In patients who received prophylaxis with low dose aspirin a single-nucleotide polymorphism in NFκB1 (rs3774968) gene was associated with increased risk of VTE (OR 3.76, 95%CI 1-16, P = 0.051). None of the patients who developed VTEs had common genetic variations that are associated with increased risk of VTEs in the general population, such as FVLeiden and FIIG20210A. Our data indicated that LMWH or vitamin K antagonists (with a target INR 2-3) effectively reduce the risk of VTEs. In patients who received prophylaxis with aspirin genetic variants of genes that are involved directly or indirectly in inflammatory response may be associated with increased risk of VTE.

Topics: Acenocoumarol; Age Factors; Antineoplastic Agents; Aspirin; Female; Genetic Predisposition to Disease; Heparin, Low-Molecular-Weight; Humans; Immunologic Factors; Lenalidomide; Male; Multiple Myeloma; NF-kappa B; Polymorphism, Single Nucleotide; Protein Subunits; Pulmonary Embolism; Thalidomide; Venous Thrombosis

To develop and validate an algorithm for the prediction of therapeutic dose of acenocoumarol in Romanian patients.. The inclusion criteria for entry to the study was age ≥ 18 years and starting acenocoumarol treatment for at least one of the following clinical indications: acute deep vein thrombosis of the lower limbs, persistent or permanent atrial fibrillation, and/or the presence of valvular prostheses requiring prolonged oral anticoagulant therapy. The patients were followed up for 3 months. Patients admitted to the internal medicine, cardiology, and geriatrics wards of the Municipal Clinical Hospital, Cluj-Napoca and "Niculae Stăncioiu" Heart Institute between October 2009 and June 2011 who fulfilled the inclusion criteria were included in the study. Clinical and demographic data that could influence the acenocoumarol stable dose were recorded for each patient. Genetic analysis included the genotyping the CYP2C9*2 and *3, and the VKORC1 -1693 G > A polymorphisms. The patients were randomly divided into two groups: (1) the main group on which the development of the clinical and genetic algorithms for acenocoumarol dose prediction was based; (2) the validation group.. The study included 301 patients, of whom 155 were women (51.5 %) and 146 were men (48.5 %). The median age of the patient cohort was 66 (women, 57; men, 73) years. After randomization the main group comprised 200 patients (66.4 %) and the validation group 101 patients (33.6 %). Age and body mass index explained 18.8 % (R (2)) of the variability in acenocoumarol weekly dose in patients in the main group. When the genetic data were added to the algorithm, the CYP2C9*2 and *3 polymorphisms and the VKORC1 -1693 G > A polymorphism accounted for 4.7 and 19. 6 % of acenocoumarol dose variability, respectively. For the main group, we calculated a mean absolute error of 5 mg/week (0.71 mg/day). In the validation group, clinical parameters explained 22.2 % of the weekly acenocoumarol dose variability. Genetic polymorphisms increased the R(2) coefficient to 32.8 %.. We have developed and validated an accurate algorithm for prediction of the stable therapeutic dose of acenocoumarol in a Romania population.

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Polymorphism, Genetic; Romania; Venous Thrombosis; Vitamin K Epoxide Reductases; White People

Venous thromboembolism is an important cause for maternal morbidity and mortality in postpartum period. Though catheter-directed thrombolysis (CDT) is now considered as a safe and effective therapy for the management of deep venous thrombosis (DVT) but still it is not indicated in postpartum DVT. We are presenting a case of 22-year-old female patient who presented with post-partum lower limb DVT and managed successfully with CDT by using injection streptokinase and temporary inferior vena caval filter was inserted as prophylactic for pulmonary embolism as she had extensive DVT extending into inferior vena cava (IVC). During follow-up, she developed large skin necrosis in left lower limb which was managed by adding injection low-molecular-weight heparin. IVC filter also could not be retrieved even after trying all manoeuvres during follow-up after 2 weeks.

Topics: Acenocoumarol; Anticoagulants; Catheterization, Peripheral; Female; Fibrinolytic Agents; Humans; Lower Extremity; Necrosis; Puerperal Disorders; Skin; Streptokinase; Vena Cava Filters; Venous Thrombosis; Young Adult

The authors present the case of a nulliparous 34-year-old patient. At the tenth week of gestation, she developed phlebothrombosis of veins of the right leg and massive pulmonary embolism. After thrombolytic and heparin therapy she developed rethrombosis and heparin-induced thrombocytopenia type II. Lepirudin was introduced in therapy and in the 12th week of gestation acenocumarol was added. After the 34th week, she received danaparoid sodium. After a week, by cesarean section, a healthy and mature female was delivered.

Topics: Acenocoumarol; Adult; Anticoagulants; Cesarean Section; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrinolytic Agents; Gestational Age; Heparin; Heparitin Sulfate; Hirudins; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Venous Thrombosis

Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves.. The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm.. We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors.. We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04).. Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Body Mass Index; Creatinine; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Genetic Markers; Genetic Variation; Genotype; Heart Valve Prosthesis; Humans; Linear Models; Male; Middle Aged; Poland; Polymorphism, Single Nucleotide; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Only few studies are available on the comparison of the efficacy and safety of the acenocoumarol and warfarin. The authors treated patients with deep vein thrombosis according to latest recommendations using D-dimer measurements and duplex ultrasound exams.. To examine the efficacy and safety of the two anticoagulants in patients with lower limb deep vein thrombosis.. The authors included 100 consecutive patients with lower limb dee deep vein thrombosis. The patients were treated with acenocoumarol or warfarin in doses to achieve INR values between 2 and 3.5 for six months. After 6 months the authors performed physical examination, D-dimer measurements and ultrasound exams, and determined the rate of unchanged thrombotic process, as well as the rate of complete and incomplete recanalisations.. There was no significant difference in the number of INR determinations during treatment between the two groups (acenocoumarol group 442, warfarin group 416). The INR values were in the therapeutic range in 71.2% and 75.4% of patients in the acenocoumarol and warfarin groups, respectively. Dose adjustment was necessary in 129 and 84 times in the acenocoumarol and warfarin groups, respectively (p = 0.0025). The therapy was optimally effective (INR value was within the therapeutic range throughout the treatment period) in 46% and 52% of patients in the acenocoumarol and warfarin groups, respectively. The thrombotic vein was completely recanalised in 91.9% of patients treated optimally, and only 80.4% of patients treated not optimally. There were 3 minor bleedings in the acenocoumarol and 4 minor bleedings in the warfarin groups, while one major bleedings occurred in both groups.. The INR values were more stable in the warfarin group than in the acenocumarole group. In both groups the rate of complete vein recanalization was related to the rate of optimally stable INR values within the therapeutic range.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; International Normalized Ratio; Lower Extremity; Male; Middle Aged; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Acenocoumarol; Edema; Heparin; Heparin, Low-Molecular-Weight; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Polycythemia; Postoperative Complications; Recurrence; Renal Dialysis; Renal Veins; Thrombectomy; Thrombolytic Therapy; Thrombophilia; Thrombophlebitis; Time Factors; Treatment Outcome; Venous Thrombosis

The authors report a case of an HIV type-1-infected patient concomitantly using highly active antiretroviral therapy and acenocoumarol anticoagulant for secondary prevention of recurrent venous thromboembolism. This is the first report of a possible drug interaction between efavirenz and atazanavir/ritonavir with acenocoumarol and also of the uncomplicated concurrent use of raltegravir with acenocoumarol.

Topics: Acenocoumarol; Alkynes; Anti-HIV Agents; Anticoagulants; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Male; Middle Aged; Oligopeptides; Pyridines; Pyrrolidinones; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Ritonavir; Venous Thrombosis

Topics: Acenocoumarol; Anticoagulants; Cell-Derived Microparticles; Female; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Middle Aged; Tinzaparin; Venous Thrombosis

A case report of young woman diagnosed as having microscopic polyangiitis (MPO) presenting with diffuse alveolar hemorrhage (DAH). DAH is a rare, but life-threatening disorder. The patients presented with dyspnea, cough, hemoptysis (not constant). The radiographic features are very characteristic and reveal the signs of diffuse, bilateral alveolar filling in chest HRCT especially in middle and lower zones. Anaemia with iron deficiency and hypoxic respiratory failure. Elevation of diffuse capacity (above 30% of predicted) is often recognized as a result of presence of blood in the alveoli. Broncho-alveolar lavage reveal haemosiderin laden macrophages. It may occurs most frequently as a secondary condition due to microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), Goodpasture syndrome. Among the many conditions it can accompany connective tissue disorders, antiphospholipid antibody syndrome, some medicines or toxic exposures.

Topics: Acenocoumarol; Anticoagulants; Diagnosis, Differential; Dyspnea; Female; Hemoptysis; Hemorrhage; Humans; Lung Diseases, Interstitial; Microscopic Polyangiitis; Venous Thrombosis

Pylephlebitis is the septic thrombosis of the portal vein. Hypercoagulability and intra-abdominal sepsis are the main predisposing factors. A 25-year-old man presented to a primary health care center complaining of fever, epigastric pain, and jaundice. He was initially diagnosed with a gastrointestinal infection and alcoholic hepatitis and, due to his unstable clinical status, was referred to the emergency room. A diagnosis of acute pylephlebitis complicated with septic shock was made. Treatment with a wide-spectrum antibiotic and anticoagulation was initiated. Fifteen days later, recanalization of the portal vein was achieved and clinical status was improved. Pylephlebitis following gastrointestinal infection is a potential cause of septic shock.

Topics: Acenocoumarol; Acute Disease; Adult; Anti-Bacterial Agents; Anticoagulants; Bacteremia; Escherichia coli Infections; Heparin; Humans; Jaundice; Male; Phlebitis; Portal Vein; Radiography; Shock, Septic; Ultrasonography; Venous Thrombosis

Topics: Acenocoumarol; Adult; Anticoagulants; Blood Proteins; Chromosomes, Human, Pair 3; DNA Mutational Analysis; Genetic Predisposition to Disease; Humans; In Situ Hybridization, Fluorescence; Male; Protein S; Protein S Deficiency; Translocation, Genetic; Venous Thrombosis

Topics: Acenocoumarol; Aggression; Anesthesia, General; Anesthetics; Anticoagulants; Contraindications; Enoxaparin; Hemodynamics; Homocystinuria; Humans; Hypoglycemia; Hypoxia; Intraoperative Complications; Male; Nitrous Oxide; Pulmonary Embolism; Seizures; Thrombophilia; Vena Cava Filters; Venous Thrombosis; Young Adult

Splanchnic vein thrombosis (SVT) is a severe complication of essential thrombocythemia (ET). No clear explanation has been given for the occurrence of thrombosis in this unusual site in patients with ET, but the existence of a specific association between unexplained SVT and the JAK2 mutation has been reported.. The present study describes SVT (portal and splenic vein thrombosis) in a young woman as the first presenting symptom of latent ET. Extensive screening for thrombophilia was negative. Our patient in fact did not fulfill the WHO diagnostic criteria for myeloproliferative disease (MPD), while she had splenomegaly and developed features suggestive of latent ET during follow-up.. In these patients with SVT, the detection of JAK2(V617F) mutation is diagnostic for masked MPD as could be documented by bone marrow histopathology. The presence of JAK2(V617F) mutation should be considered per se a prothrombotic state for cerebral, coronary and peripheral microvascular disturbances and for SVT but not for deep vein thrombosis. Anticoagulation is the treatment of choice for all SVT and proper treatment of the MPD is recommended in patients with SVT associated with the JAK2(V617F) mutation.

Topics: Abdominal Pain; Acenocoumarol; Adult; Anticoagulants; Biopsy; Bone Marrow; Bone Marrow Examination; Epilepsy; False Negative Reactions; Female; Heparin; Humans; Hydroxyurea; Janus Kinase 2; Polycystic Ovary Syndrome; Portal Vein; Splenic Vein; Splenomegaly; Thrombocythemia, Essential; Thrombophilia; Venous Thrombosis

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Drug Resistance; Genotype; Humans; Male; Venous Thrombosis; Warfarin

We present a case of septicaemia caused by Arcanobacterium haemolyticum in a previously healthy 23-year-old man suffering from acute pharyngotonsillitis, who developed complicated Lemierre's syndrome. Three blood cultures (both aerobic and anaerobic) revealed the exclusive presence of A. haemolyticum. The presence of Fusobacterium necroforum was not essential for the development of this pathology. To our knowledge, this is the first reported case of Lemierre's syndrome caused solely by A. haemolyticum. We confirm that this organism must be considered a potential pathogen in immunocompetent patients.

Topics: Acenocoumarol; Actinomycetales Infections; Anti-Bacterial Agents; Anticoagulants; Arcanobacterium; Brain Abscess; Humans; Jugular Veins; Male; Sepsis; Venous Thrombosis; Young Adult

A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+/-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+/-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+/-1.9 mg) than the noncarriers (4.1+/-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

Topics: Acenocoumarol; Adult; Alleles; Anticoagulants; Atrial Fibrillation; Base Sequence; DNA Primers; Dose-Response Relationship, Drug; Drug Resistance; Female; Gene Frequency; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Poland; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Pulmonary Embolism; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

To identify the frequencies of the polymorphisms CYP2C9*2, CYP2C9*3 and VKORC1-1639 G>A in the Greek population and investigate whether these polymorphisms and patient demographics (age, sex and comedication) could explain the interindividual variability of acenocoumarol dose requirements for efficient anticoagulation.. CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A allelic variants were analyzed in 98 patients treated with acenocoumarol.. Allelic frequencies of CYP2C9*2, CYP2C9*3 and VKORC1A were found to be 0.155, 0.075 and 0.485, respectively. Carriership of at least one CYP2C9*3 allele led to the most pronounced reduction in the required mean dose (p<0.0001). In contrast, the CYP2C9*2 allele played a minor role (p=0.3). VKORC1 A/A patients needed approximately a third of the dose required by wild-type patients to achieve the target INR (p<0.0001). Age was the only demographical factor significantly affecting acenocoumarol dose (p<0.0001). In a multivariable regression model, CYP2C9, VKORC1 genotypes and age explained 55% of acenocoumarol dosing variability.. VKORC1-1639G>A, CYP2C9*2 and CYP2C9*3 polymorphisms were found to predispose to acenocoumarol sensitivity in Greeks. Other hereditary and nongenetic parameters must be incorporated in an individualized dosing algorithm to achieve a safer anticoagulant effect.

Topics: Acenocoumarol; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cohort Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Gene Frequency; Greece; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Single Nucleotide; Pulmonary Embolism; Regression Analysis; Retrospective Studies; Venous Thrombosis; Vitamin K Epoxide Reductases

The recommended treatment in patients with primary antiphospholipid syndrome (APS) after a thrombotic event is long-term anticoagulation. However, it is still not exactly known how to manage patients who remain stable for years and whose antiphospholipid antibodies (APA) decrease until becoming negative. This study aims to assess the course of the primary APS in a group of patients after anticoagulation therapy is discontinued.. Ten patients with primary APS who had developed deep venous thrombosis in the limbs (9) or in the aorta (1) were included. After a minimum period of 12 months of anticoagulation therapy, this was discontinued if the patients were negative APA during the follow-up in two consecutive measurements.. Six patients (60%) developed persistent negative APA. Four had transient risk factors (2 pregnant, 1 immobilization, 2 oral contraceptives). No new thrombosis episode was observed after a follow-up period of 21 +/- 4.9 months.. Our data suggest that anticoagulation can be discontinued in those patients with primary APS and persistent negative APA, especially if the thrombotic event was venous and occurred in association with a transient risk factor, such as immobilization or pregnancy. Extensive studies are required to confirm these results.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Retrospective Studies; Venous Thrombosis

Oral anticoagulation with coumarin derivatives (OAC) has been used for more than 50 years and is being prescribed to a steadily increasing number of patients as a long-term therapy. The aim of our study was to evaluate patients' knowledge about the safety of acenocumarol treatment, the therapeutic range of International Normalized Ratio (INR) and its interactions with other medications and food.. One hundred and forty patients on long-term acenocumarol treatment were included in the study. They were interviewed using a questionnaire specifically prepared by the authors. The questions concerned their understanding of the reasons for the treatment, knowledge of target INR ratio, frequency of INR examination. Additionally the questionnaire contained questions specifically designed to check the patients' knowledge about factors influencing INR values e.g. drugs, food, alcohol and the like.. One hundred and fifteen (82.1%) patients declared knowledge of target INR ratio, but only eighty eight (62.9%) answered correctly. Percentages of correct answers for the questions evaluating knowledge about acenocumarol treatment did not exceed 50%. Patients' responses suggested that advice was not always provided by doctors.. Level of patients' knowledge about the safety of OAC treatment was very low. Insufficient knowledge was observed particularly in patients with lower education levels and those over 60 years of age. Those groups require a special attention and longer education to be able to self-manage the treatment. Special anticoagulant clinics do not exist in Poland. So, it seems very appropriate to develop concise guidelines available for patients in practices of family doctors. Education should be systematic and modified according to changing recommendations.

Topics: Acenocoumarol; Anticoagulants; Chronic Disease; Drug Administration Schedule; Drug Interactions; Educational Measurement; Health Knowledge, Attitudes, Practice; Herb-Drug Interactions; Humans; International Normalized Ratio; Patient Education as Topic; Poland; Self Care; Surveys and Questionnaires; Venous Thrombosis

Topics: Acenocoumarol; Administration, Oral; Adult; Anticoagulants; Collateral Circulation; Diagnosis, Differential; Femoral Vein; Fever; Humans; Hyperplasia; Iliac Vein; Kidney; Magnetic Resonance Imaging; Male; Radiography, Abdominal; Radiography, Thoracic; Renal Veins; Syndrome; Tomography, X-Ray Computed; Ultrasonography, Doppler; Vena Cava, Inferior; Venous Thrombosis

A 34-year-old patient underwent a knee exarticulation amputation and developed symptoms of pain, redness and swelling of the stump in combination with a feeling of tightness in the chest. These symptoms were first attributed to muscle pain and exertion but further examination revealed deep venous thrombosis (DVT) of the stump and a pulmonary embolism for which he was treated with nadroparine and acenocoumarol. Shortly after treatment he could resume the use of the prosthesis. A DVT in the amputation stump is not frequently encountered, but is a serious complication that can, together with a pulmonary embolism, be life threatening. The literature mentions an incidence ranging from 0-12%. Physical examination is often not conclusive and further examination of the patient with duplex scanning is necessary, with a ventilation-perfusion scan if a pulmonary embolism is suspected. Patients with a lower extremity amputation have a higher risk of developing a DVT because of immobility and increased venous pooling in the residual limb. Symptoms of a red, swollen, warm and painful stump should trigger the physician to suspect a DVT.

Topics: Acenocoumarol; Adult; Amputation Stumps; Amputation, Surgical; Anticoagulants; Humans; Male; Nadroparin; Treatment Outcome; Venous Thrombosis

Topics: Acenocoumarol; Aged; Angioedema; Autoantibodies; Complement C1 Inhibitor Protein; Danazol; Factor V; Female; Follow-Up Studies; Heterozygote; Humans; Nifedipine; Recurrence; Venous Thrombosis

Temporary interruption of oral anticoagulation to perform invasive procedures is a frequently occurring medical problem. There are only a few studies available on the optimal clinical approach in this situation. The published clinical studies and guidelines are summarized.

Topics: Acenocoumarol; Anticoagulants; Dose-Response Relationship, Drug; Endoscopy; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Minor Surgical Procedures; Practice Guidelines as Topic; Pulmonary Embolism; Risk Factors; Secondary Prevention; Venous Thrombosis; Vitamin K; Warfarin

Several factors are associated with an increased risk of recurrent venous thromboembolism (VTE). The aim of the study was to investigate whether the quality of oral anticoagulation therapy (OAT) is a long-term risk factor for recurrence of VTE after OAT interruption.. A total of 297 patients (170 males) with a recent acute unprovoked VTE episode were prospectively monitored during OAT in our anticoagulation clinic and followed up for 21 months after OAT interruption. Recurrent events were recorded in 42 subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt-y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT duration. Subjects experiencing recurrence after OAT interruption had spent significantly more time at markedly subtherapeutic international normalized ratio (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR) during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95% confidence interval (CI) 1.49-5.18; P = 0.001) and 2.70 (95% CI 1.39-5.25; P = 0.003) at univariate and multivariate analysis, respectively] in those who spent more time (upper quintile) at INR values <1.5, being especially evident in the first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI 1.07-3.96; P = 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P = 0.056)] analysis when the entire OAT period was considered. Subjects in the upper quintile of time spent at INR values <1.5 had significantly higher D-dimer values when OAT was stopped and after 3 months.. The amount of time that subjects with an acute unprovoked VTE event spend at near-normal INR values (<1.5) during the first 3 months of treatment is associated with higher D-dimer values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrence.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Pulmonary Embolism; Recurrence; Regression Analysis; Risk; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Catchment Area, Health; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Prospective Studies; Risk Factors; Rural Population; Spain; Time; Venous Thrombosis

Topics: Acenocoumarol; Anticoagulants; Drug Administration Schedule; Humans; Liver Cirrhosis; Male; Middle Aged; Recurrence; Tomography, X-Ray Computed; Venous Thrombosis

We report on a 20-year-old man presenting with priapism while receiving oral acenocoumarol for the treatment of deep vein thrombosis. To the authors' knowledge, it is the first reported case of acenocoumarol-associated priapism.

Topics: Acenocoumarol; Adult; Anticoagulants; Humans; Male; Priapism; Ultrasonography, Doppler; Venous Thrombosis

Recently there are several evidence based facts about the beneficial effect of oral anticoagulant therapy in patients with cardiovascular diseases. In the other hand the often serious bleeding complications as well as the ineffective antithrombotic therapy should be avoided.. Authors had examined with a questionnaire some characteristic parameters of oral anticoagulant therapy in Hungarian hospitals. Based on the results they carried out a retrospective survey (488 consecutive patients) on the accuracy and other peculiarity of long-term acenocoumarol therapy in the district of County Hospital Gyula.. Mean value of all coagulation test's results (INR: 2.72 +/- 1.07, prothrombin %: 36.11 +/- 10.52) suggest a relatively favourable therapeutic activity in the patients required acenocoumarol therapy. According to their data the proportion of newly introduced anticoagulant therapy secondary to atrial fibrillation was highly increased (42%). They stated that the accuracy of documentation in conducting of oral anticoagulant therapy should be improved and it would be the time to use obligatory the INR value in the clinical practice. They found the best therapeutic punctuality among the patients controlled in the Special Cardiological Outpatient Department. There were relatively few event of serious bleedings. The authors called attention to the patients (about 5%) who were treated without any special cause for a longer period of time than it was necessary. They emphasize the pivotal role of permanent education of patients and the importance of their therapeutic compliance in the appropriate oral anticoagulant control.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Hungary; International Normalized Ratio; Male; Middle Aged; Outpatients; Patient Compliance; Patient Education as Topic; Prothrombin; Quality of Health Care; Retrospective Studies; Surveys and Questionnaires; Thromboembolism; Venous Thrombosis

We evaluated the influence of aging, gender and indications of anticoagulant therapy on acenocoumarol requirements in 1845 patients from 30 to 99 years old receiving acenocoumarol therapy who were monitored in our hospital outpatient anticoagulation clinic from March 1993 through September 1999. The patients were stratified in seven age groups, comprising older than 80 years and the five decades between 30 years and 80 years. We found a progressive decrease in the acenocoumarol requirements from 30 years to 80 years (rho=-0.98), which was estimated as 2.7 mg/week per decade (11.5% per decade). This decrease was not the consequence of a different range of anticoagulation or differences in body weight. We did not find correlation between the decrease of acenocoumarol requirements and different biochemical parameters including, creatinine, calcium and alanine aminotransferase. We detected a progressive decrease in levels of serum total proteins but changes in this parameter did not correlate with the amount of acenocoumarol requirements. The dose of acenocoumarol (mg/week per patient) of those patients suffering from venous thromboembolism were higher than the remainder of the patients (18.4 +/- 9.3 versus 14.5 +/- 7.8, P <0.0001). This finding was also detected, after stratifying the patients by decades, from 60 years to 80 years. In conclusion, requirements of acenocoumarol decrease with aging; this decrease represents an important amount from 30 years to 80 years and it should be kept in mind to choose the initial dose of acenocoumarol. Patients with venous thromboembolism required a higher dose of acenocoumarol.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Aging; Anticoagulants; Blood Proteins; Drug Monitoring; Female; Humans; Male; Middle Aged; Retrospective Studies; Thromboembolism; Venous Thrombosis

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Bias; Dalteparin; Humans; International Normalized Ratio; Secondary Prevention; Thrombocytopenia; Thromboembolism; Venous Thrombosis

To evaluate and compare the efficacy and safety of low molecular weight heparin (LMWH) (nadroparine) and acenocoumarol in the treatment of deep venous thrombosis (DVT).. A retrospective study of the case notes of 105 patients (68 men) with established DVT who had been hospitalised during a 6-year period in a university hospital department.. Among 105 patients, 65 received nadroparine and the remaining intravenous unfractionated heparin (UH) as initial treatment. Twenty-seven patients out of 65 continued their treatment with nadroparine and the remaining 78 patients (38 initially treated with LMWH and 40 with UH) with acenocoumarol. The average hospital stay for those on LMWH treatment was 2.2 +/- 1.4 days in comparison to 6.4 +/- 1.2 days for those treated with acenocoumarol (p < 0.001). During the home-based phase of treatment, 14 patients were re-admitted to hospital for recurrent DVT; ten and four of those treated with acenocoumarol and LMWH, respectively (p = NS). Haemorrhagic complications occurred in 12 of the patients who received acenocoumarol and in one of those on LMWH (p = NS).. The patients who received LMWH had a significantly lower duration of hospitalisation than those who received acenocoumarol. There were no significant differences between the administration of LMWH and acenocoumarol in terms of efficacy or safety in patients with DVT.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Female; Humans; Injections, Intravenous; Length of Stay; Male; Middle Aged; Nadroparin; Retrospective Studies; Venous Thrombosis

Topics: Acenocoumarol; Citalopram; Depression; Drug Interactions; Female; Gingival Hemorrhage; Humans; International Normalized Ratio; Middle Aged; Venous Thrombosis

To report a clinically severe interaction between ritonavir (RTV) and acenocoumarol resulting in a decrease in the anticoagulant effect severe enough to eventually preclude RTV administration.. An asymptomatic, HIV-infected, 46-year-old man with mitraortic prosthetic valves receiving acenocoumarol therapy started stavudine, lamivudine, and RTV 600 mg twice daily. His international normalized ratio (INR) decreased dramatically (the opposite of what should be expected). Although the acenocoumarol dose was progressively increased to 3 times the original dose, it was impossible to achieve the previous INR and RTV was withdrawn.. RTV is an inducer of the hepatic isoenzymes CYP1A2, CYP1A4, and CYP2C9/19 and leads to extensive metabolism of acenocoumarol that cannot be balanced by dose increases. This effect is the opposite of what was expected to occur, considering that RTV is also a strong inhibitor of most hepatic isoenzymes.. RTV severely decreases the anticoagulant effect of acenocoumarol. It must be added to the list of drugs that affect the action of oral anticoagulants, and it probably should be avoided in patients receiving acenocoumarol.

Topics: Acenocoumarol; Anticoagulants; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; International Normalized Ratio; Male; Middle Aged; Ritonavir; Venous Thrombosis

Topics: Acenocoumarol; Anticoagulants; Dose-Response Relationship, Drug; Drug Costs; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Nadroparin; Recurrence; Venous Thrombosis; Warfarin

Topics: Acenocoumarol; Anticoagulants; Humans; Hyperhomocysteinemia; Leg; Male; Middle Aged; Recurrence; Venous Thrombosis

To investigate the management of (suspected) deep vein thrombosis in general practice.. Self completing postal questionnaire among a random sample of 692 general practitioners in the Netherlands.. The overall response rate was 58%. Eighty-nine percent of the respondents initiated objective evaluation. Less than 3% usually make the diagnosis on clinical grounds only. Ninety-two percent initiated adequate treatment for the last patient with deep vein thrombosis. No more than 4% usually treat patients with acenocoumarol alone. Respondents frequently referred a patient to a specialist, 41% to confirm the diagnosis and 85% for treatment. Already 44% feel that management of deep vein thrombosis is a mandate of the general practitioner. For those who do not, the availability of diagnostic and therapeutic facilities are the main obstacles.. In general practice objective diagnostic methods to evaluate suspected deep vein thrombosis are routinely used and patients receive adequate treatment. Although patients are frequently referred to the hospital many general practitioners feel that they should be able to take care of these patients themselves. (See Editorial p. 133)

Topics: Acenocoumarol; Adult; Anticoagulants; Attitude of Health Personnel; Clinical Competence; Drug Utilization; Family Practice; Female; Humans; Male; Middle Aged; Netherlands; Physicians, Family; Practice Patterns, Physicians'; Referral and Consultation; Surveys and Questionnaires; Venous Thrombosis

Authors study the risk diseases in dental practice. They analyze the possible complications and the methods of their prevention in each risk group. They take deal with the importance of antibiotic prophylaxis, the problems of local anaesthesia and the management of patients who suffer from coagulation disturbances. They present the management of risk patients in two cases. They emphasize the importance of anamnestic history in every case before dental treatment.

Topics: Acenocoumarol; Adult; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation Disorders; Blood Loss, Surgical; Dental Care; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Nadroparin; Postoperative Complications; Risk Factors; Tooth Extraction; Venous Thrombosis; Vestibuloplasty

Two patients with developing venous gangrene of the lower extremity and contraindications to systemic thrombolytic therapy are presented. Low-dose intraarterial burst therapy with urokinase provided rapid amelioration of symptoms and avoided amputation without any serious bleeding complications in both patients.

Topics: Acenocoumarol; Adult; Anticoagulants; Contraindications; Female; Gangrene; Heparin; Humans; Infusions, Intra-Arterial; International Normalized Ratio; Leg; Leg Ulcer; Plasminogen Activators; Shock, Septic; Thrombolytic Therapy; Thrombophlebitis; Ultrasonography; Urokinase-Type Plasminogen Activator; Venous Thrombosis

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve; Female; Fibrinolytic Agents; Heart Valve Prosthesis Implantation; Hematoma; Heparin; Humans; Psoas Muscles; Radiography; Venous Thrombosis

Topics: Acenocoumarol; Anticoagulants; Dicumarol; Drug Therapy; Heparin; Phenindione; Postoperative Complications; Preventive Medicine; Pulmonary Embolism; Thrombophlebitis; Toxicology; Venous Thrombosis; Vitamin K 1; Warfarin

Topics: Acenocoumarol; Anticoagulants; Budd-Chiari Syndrome; Endotoxins; Escherichia coli Infections; Heparin; Hirudins; Hyperlipidemias; Pharmacology; Prothrombin Time; Rats; Research; Salmonella Infections; Salmonella Infections, Animal; Thrombophlebitis; Toxicology; Venous Thrombosis

Topics: Abdomen; Abdominal Cavity; Acenocoumarol; Anticoagulants; Humans; Postoperative Care; Thrombophlebitis; Venous Thrombosis