acenocoumarol and Thromboembolism

Vitamin-K antagonists (VKAs) have remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. The management of treatment with VKAs is challenging due to their narrow therapeutic index and the wide interindividual variation in response to therapy. Variants of the

Topics: Acenocoumarol; Anticoagulants; Cytochrome P-450 CYP2C9; Genotype; Homozygote; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Thromboembolism; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Vitamin K antagonist (VKA) is a commonly prescribed anticoagulant with a narrow therapeutic window. Genetic polymorphisms account for high VKA dosage variability. Hence, we performed an updated meta-analysis of all randomized clinical trials (RCTs) comparing genotype-guided VKA versus standard dosing algorithms. We conducted a systematic search of electronic databases from inception to October 2017 for all RCTs. The primary outcome was the percentage of time in therapeutic range (TTR). Secondary outcomes were international normalized ratio >4, major and all bleeding events, thromboembolism, adverse and serious adverse events, and all-cause mortality. We calculated the weighted mean difference for the primary outcome and risk ratio (RR) for secondary outcomes using a random-effect model. We included 20 RCTs and analyzed a total of 5,980 adult patients. Our pooled analysis showed greater improvement in TTR for the genotype-guided group in comparison with the standard group (mean difference 3.41%, 95% confidence interval [CI] 0.71 to 6.10, p = 0.01). In addition, there were significant reductions in major and all bleeding events ((RR 0.35, 95% CI 0.20 to 0.63, p = 0.0004) and (RR 0.79, 95% CI 0.66 to 0.95, p = 0.01), respectively). However, there were no significant differences between the groups for international normalized ratio >4 (RR 0.89, 95% CI 0.80 to 1.00, p = 0.06), thromboembolism (RR 0.81, 95% CI 0.56 to 1.17, p = 0.25), serious adverse events (RR 0.79, 95% CI 0.61 to 1.03, p = 0.08), any adverse events (RR 0.94, 95% CI 0.88 to 1.01, p = 0.07), or all-cause mortality (RR 0.73, 95% CI 0.32 to 1.66, p = 0.46). In conclusion, genotype-guided VKA dosing can improve the TTR and reduce the risk for bleeding episodes, in comparison with standard dosing algorithms.

Topics: Acenocoumarol; Anticoagulants; Cause of Death; Genotype; Hemorrhage; Humans; International Normalized Ratio; Mortality; Odds Ratio; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenprocoumon; Thromboembolism; Vitamin K; Warfarin

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

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

Anticoagulant treatment is required for the treatment and prevention of thromboembolic disorders. Vitamin K antagonists are commonly used oral anticoagulants worldwide. Acenocoumarol is mono-coumarin derivative with racemic mixture of R (+) and S (-) enantiomers. Efficacy and safety of acenocoumarol has been evaluated in atrial fibrillation, cardiac valve replacement, after myocardial infarction, treatment of deep vein thrombosis, after major surgeries and after critical illness requiring prolonged hospitalization. Acenocoumarol is effective and safe in all age groups. It offers an advantage over warfarin in terms of better stability of anti-coagulant effect. Due to its economic advantage acenocoumarol may be suitable oral anticoagulant for long term use in countries like India.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; India; Mixed Function Oxygenases; Myocardial Infarction; Thromboembolism; Treatment Outcome; Vitamin K

Recent studies suggest that sickle cell disease (SCD) is a hypercoagulable state contributing to vaso-occlusive events in the microcirculation, resulting in acute and chronic sickle cell-related organ damage. In this article, we review the existing evidence for contribution of hemostatic system perturbation to SCD pathophysiology. We also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of venous thromboembolism. Finally, the potential role of platelet inhibitors and anticoagulants in SCD is briefly reviewed.

Topics: Acenocoumarol; Anemia, Sickle Cell; Anticoagulants; Hemostasis; Hemostatics; Humans; Thromboembolism; Treatment Outcome

To evaluate the therapeutic impact of an education program on patients undergoing oral anticoagulation treatment, within the hospital of Annecy (France).. Groups of 10 patients were invited to participate to two meetings. The education was carried out by two nurses. Thanks to this prospective study, we compare the population before and after education in terms of treatment knowledge and stability.. Within 9 months 88 patients have been included, amongst which 55 have attended the two meetings. The average of correct answers to the knowledge evaluation questionnaire distributed before and after 6 months of education were, respectively, 6.63/12, 10.09/12 (P < 0.0001). Through INR controls within the 6 months preceding (424 controls) and the 6 months following the education (619 controls), we observe: an increase of the total INR average in therapeutic zone, from 45% to 61% (P < 0.0001); a decrease of the difference average per patient between the INR value observed and the one targeted: 0.54 before education, 0.40 after education (P = 0.0016); at last, the average phasing per patient under the therapeutic zone increases after education, from 49% to 65% (P < 0.001).. The education improves objectively the knowledge of patient undergoing AVK. If the size of patient sample is not large enough to prove any consequence on hemorrhagic or thrombotic complications, the education program still improves significantly the treatment stability.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Chi-Square Distribution; Data Interpretation, Statistical; Female; Heart Diseases; Humans; Male; Middle Aged; Patient Education as Topic; Patient Satisfaction; Phenindione; Surveys and Questionnaires; Thromboembolism; Time Factors; Vitamin K

Topics: Acenocoumarol; Angina Pectoris; Anticoagulants; Cerebrovascular Disorders; Dicumarol; Heparin; Humans; Myocardial Infarction; Phlebitis; Rheumatic Heart Disease; Thromboembolism; Thrombophlebitis; Warfarin

The first-line drugs for the treatment of non-valvular atrial fibrillation (AF) are non-vitamin K antagonist oral anticoagulants (NOACs), which are preferred over vitamin K antagonists (VKAs). There is some evidence that there are dis-crepancies between everyday clinical practice and the guidelines.. The study aimed to compare the characteristics of patients on VKAs, dabigatran, and rivaroxaban in everyday practice (i.e. baseline characteristics, drug doses, risk factors for bleeding and thromboembolic events). Additionally, we assessed the frequency of prescription of different oral anticoagulants (OACs) in recent years.. This study consisted of data from the multicentre CRAFT (MultiCentre expeRience in AFib patients Treated with OAC) study (NCT02987062). This was a retrospective analysis of hospital records of AF patients (hospitalised in the years 2011-2016) treated with VKAs (acenocoumarol, warfarin) and NOACs (dabigatran, rivaroxaban). A total of 3528 patients with non-valvular AF were enrolled in the CRAFT study.. The total cohort consisted of 1973 patients on VKA, 504 patients on dabigatran, and 1051 patients on rivaroxaban. Patients on rivaroxaban were older (70.5 ± 13.1 years) and more often female (47.9%), compared with those on VKAs (67.0 ± 12.8 years, p < 0.001; 35.5%, p < 0.001) and on dabigatran (66.0 ± 13.9 years, p < 0.001; 38.9%, p = 0.001). Among NOACs, patients with persistent and permanent AF were more likely to receive rivaroxaban (54.7% and 73.4%, re-spectively) than dabigatran (45.3%, p < 0.001 and 26.6%, p = 0.002, respectively). Patients on rivaroxaban had higher risk of thromboembolic events (CHA2DS2VASc 3.9 ± 2.0, CHADS2 2.2 ± 1.4) than those on VKAs (3.3 ± 2.0, 1.9 ± 1.3) and on dabigatran (3.1 ± 2.0, 1.8 ± 1.3). Patients on rivaroxaban had also a higher rate of prior major bleeding (11.2%) than those on VKAs (6.7%, p < 0.001) and on dabigatran (7.3%, p = 0.02). Patients on lower doses of dabigatran and rivaroxaban had a significantly higher risk of thromboembolic and bleeding events. Use of VKAs in the year 2011 was reported in over 96% of patients on OACs, but this proportion decreased to 34.6% in 2016. In the last analysed year (2016) AF patients were treated mainly with NOACs - dabigatran (24.2%) and rivaroxaban (41.3%).. The prescription of VKAs declined significantly after the introduction of NOACs. Patients treated with different OACs demonstrated a distinct baseline clinical profile. The highest risk of thromboembolic events and incidence of major bleedings was observed in patients on rivaroxaban, in comparison to patients on VKAs and dabigatran. Among NOACs, patients treated with lower doses of dabigatran and rivaroxaban were older and had a significantly higher risk of thromboembolic and bleeding events.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Thromboembolism; Warfarin

Reversal of anticoagulation can be needed in patients undergoing heart valve surgery. ROTEM® has been correlated with international normalized ratio (INR) in patients on warfarin but not with patients on acenocoumarol. This study investigates the reliability of ROTEM® for detecting INR values below the 1.5 threshold in patients on acenocoumarol therapy.. Patients on oral anticoagulation with acenocoumarol after elective heart valve replacement were prospectively included in the study. INR and the ROTEM® were measured simultaneously. ROTEM® parameters included coagulation time, clot formation time, alpha angle, and maximal clot firmness after tissue factor activation (EXTEM). Concordance between INR and ROTEM® was analyzed by Lin's concordance coefficient (LCC) and the correlation with Spearman's rho.. Fifty-four consecutive patients (40 female; median age 67years) were included. Clotting time (CT) was the parameter that best correlated with INR (r=0.81, p<0,001), and LCC was substantial (0.67). CT was able to predict INR values above or below 1.5: area under curve=0.998. CT≥84seconds, corresponding to a cut-off for likelihood ratio (LR+)=5, had a sensitivity and specificity of 100% and 80%, respectively, to detect an INR below 1.5. For the same INR threshold, CT≥84seconds had a predictive positive value of 92.9% and a predictive negative value of 100%.. Our preliminary results suggest that CT≥84seconds in the EXTEM ROTEM® test is a feasible method for predicting an insufficient reversion of oral anticoagulant therapy in patients taking acenocoumarol after elective heart valve surgery.

Topics: Acenocoumarol; Aged; Anticoagulants; Drug Administration Schedule; Drug Monitoring; Drug Tolerance; Elective Surgical Procedures; Female; Humans; International Normalized Ratio; Male; Middle Aged; Postoperative Hemorrhage; Reproducibility of Results; Sensitivity and Specificity; Thrombelastography; Thromboembolism; Treatment Outcome

Observational evidence suggests that the use of a genotype-guided dosing algorithm may increase the effectiveness and safety of acenocoumarol and phenprocoumon therapy.. We conducted two single-blind, randomized trials comparing a genotype-guided dosing algorithm that included clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included only clinical variables, for the initiation of acenocoumarol or phenprocoumon treatment in patients with atrial fibrillation or venous thromboembolism. The primary outcome was the percentage of time in the target range for the international normalized ratio (INR; target range, 2.0 to 3.0) in the 12-week period after the initiation of therapy. Owing to low enrollment, the two trials were combined for analysis. The primary outcome was assessed in patients who remained in the trial for at least 10 weeks.. A total of 548 patients were enrolled (273 patients in the genotype-guided group and 275 in the control group). The follow-up was at least 10 weeks for 239 patients in the genotype-guided group and 245 in the control group. The percentage of time in the therapeutic INR range was 61.6% for patients receiving genotype-guided dosing and 60.2% for those receiving clinically guided dosing (P=0.52). There were no significant differences between the two groups for several secondary outcomes. The percentage of time in the therapeutic range during the first 4 weeks after the initiation of treatment in the two groups was 52.8% and 47.5% (P=0.02), respectively. There were no significant differences with respect to the incidence of bleeding or thromboembolic events.. Genotype-guided dosing of acenocoumarol or phenprocoumon did not improve the percentage of time in the therapeutic INR range during the 12 weeks after the initiation of therapy. (Funded by the European Commission Seventh Framework Programme and others; EU-PACT ClinicalTrials.gov numbers, NCT01119261 and NCT01119274.).

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Female; Follow-Up Studies; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Phenprocoumon; Single-Blind Method; Thromboembolism; Treatment Failure; Vitamin K Epoxide Reductases

To evaluate postoperative bleeding and thromboembolic complications during dental extractions in anticoagulated patients, using 2 different protocols.. In total, 214 anticoagulated patients in need of simple dental extractions were randomized into 2 groups. Group A consisted of 109 patients on continuous oral anticoagulation therapy (OAT), with a mean international normalized ratio (INR) of 2.45 +/- 0.54. Local hemostasis in these patients was achieved with resorbable collagen sponges, without wound suturing. Group B consisted of 105 patients on bridging therapy with low-molecular-weight heparin (nadroparin-calcium), with a mean INR of 1.26 +/- 0.11 on the day of the procedure. Neither local hemostatic agents nor suturing of the wound was used in these patients.. Eight (7.34%) patients in group A and 5 (4.76%) patients in group B manifested postextractional bleeding, without statistical significance (chi(2), Yates' = 0.253, P > .05). All cases of hemorrhage were mild and easily controlled using local hemostatic measures. None of the participants in either group experienced thromboembolic complications.. In patients receiving OAT with an INR

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Anticoagulants; Female; Hemostatic Techniques; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Nadroparin; Postoperative Hemorrhage; Thromboembolism; Tooth Extraction; Warfarin; Young Adult

Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists.. Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655.. The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD 5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; p<0.0001). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0.014); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0.9 vs 1.3 per 100 patient-years; hazard ratio 0.71, 95% CI 0.39-1.30; p=0.007), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3.2 vs 2.9 per 100 patient-years; p=0.49).. In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Oligosaccharides; Risk Factors; Single-Blind Method; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Control of oral anticoagulant treatment has been reported to be suboptimal, but previous studies suggest that patient self-management improves control.. To compare the quality of control and the clinical outcomes of oral anticoagulant treatment in self-managed patients versus patients following conventional management.. Randomized, controlled trial.. University-affiliated hospital in Spain.. 737 patients with indications for anticoagulant treatment.. The self-management group (n = 368) received simple instructions for using a portable coagulometer weekly and self-adjusting treatment dose. The conventional management group (n = 369) received usual care in an anticoagulation clinic (monthly measurement and control of international normalized ratio [INR], managed by hematologists).. Percentage of INR values within the target range and major related complications.. The median follow-up period was 11.8 months (range, 0.3 to 16.9 months). The unadjusted percentages of in-range INRs were 58.6% in the self-management group and 55.6% in the conventional management group (difference, 3.0 percentage points [95% CI, 0.4 to 5.4 percentage points]). Twenty-seven patients (7.3%) in the conventional management group and 8 (2.2%) in the self-management group had major complications related to anticoagulant treatment. The unadjusted risk difference for major complications between groups was 5.1 percentage points (exact 95% CI, 1.7 to 8.5 percentage points). Fewer patients had minor hemorrhages in the self-management group (14.9%) than in the conventional management group (36.4%). Fifteen patients (4.1%) in the conventional management group and 6 (1.6%) in the self-management group died (unadjusted risk difference, 2.5 percentage points [exact 95% CI, 0.0 to 5.1 percentage points]).. The trial was performed at only 1 center and was not blinded. The dropout rate in the intervention group was 21%.. Compared with conventional management by an anticoagulation clinic, self-management of oral anticoagulant treatment achieved a similar level of control. Of note, major complications and minor hemorrhages were less common in the self-management group.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Monitoring, Physiologic; Patient Compliance; Patient Dropouts; Patient Education as Topic; Risk Factors; Self Care; Thromboembolism; Treatment Outcome

Antiplatelet agents are used for prevention of thromboembolism in surgical patients and in patients with chronic atrial fibrillation. Up to date, however, results of randomized studies comparing antiplatelet agents and oral anticoagulation have not been reported. The aim of this study was to compare the efficacy and safety of triflusal (an antiplatelet agent) versus acenocoumarol for primary prevention of thromboembolism in the early postoperative period after implantation of a bioprosthesis.. In this prospective, multicentric, randomized, open pilot trial, patients were assigned to treatment with triflusal (600mg/d) or acenocoumarol (target INR 2.0-3.0). Study medication was started 24-48h after valve replacement with a bioprosthesis, and continued for 3 months. Four follow-up visits were scheduled: baseline, and at 1, 3 and 6 months thereafter. The primary end-point was a composite of the rate of thromboembolism, severe hemorrhage and valve-related mortality.. A total of 193 patients were included (97 received triflusal and 96 acenocoumarol), with a mean age of 72.5 years. Half were men. Aortic valve replacement was performed in 181 patients (93.8%), mitral valve replacement in 10 patients (5.2%) and double valve replacement in 2 (1.0%). Hospital mortality was 11 (5.7%). Primary outcome was recorded in 9 patients with triflusal (9.4%) and in 10 patients with acenocoumarol (11%). There were nine episodes (4.7%) of thromboembolism, six in the triflusal group and three in the acenocoumarol group, and three episodes of permanent neurological deficits, one in the triflusal group and two in the acenocoumarol group. Severe hemorrhage: nine episodes, six in the acenocoumarol group and three in the triflusal group. None of the observed differences in efficacy were statistically significant. Regarding safety, three patients in triflusal group reported at least one hemorrhage, compared to 10 in acenocoumarol group (P=0.048).. There were no significant differences in efficacy between both groups, however, triflusal showed a significantly lower incidence of bleeding episodes.

Topics: Acenocoumarol; Aged; Anticoagulants; Bioprosthesis; Epidemiologic Methods; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Hemorrhage; Salicylates; Thromboembolism

We checked the feasibility of self-screening for atrial fibrillation (AF) by instructed patients pts and prompt home self-administration of an initial dose of low-molecular weight heparin (LMWH) prior to seeking medical attention.. Pts with persistent AF and low risk of systemic embolisation qualified to elective cardioversion (CV) were the subjects of our interest. All pts were trained to identify AF by palpation of the radial pulse and to self-inject LMWH in case of arrhythmia recurrence. 232 pts (mean age 59.8 +/- 8.6 years) who maintained sinus rhythm (SR) during 4 weeks following successful cardioversion (CV) and correctly recognized AF recurrence and those without episodes of AF were equipped with nadroparine after acenocoumarol discontinuation. Thromboembolic prophylaxis was continued with antiplatelets agents or those no additional risk factors of systemic embolisation were left without medical therapy.. 191 pts had AF recurrence during the mean 2.6 +/- 1.7 years observation period, 172 of them correctly identified AF episode, including 162 who performed LMWH injections at home. 7 pts, who had performed LMWH injections, presented with SR on arrival to hospital, 6 pts had AF1.2 out of 21 pts who failed to identify their AF episodes and 1 pt of those who correctly detected the AF recurrence but failed to perform LMWH self-injection suffered from ischemic stroke (sensitivity 96.1%, specificity 60.4%). No side effects of domiciliary LMWH self-injection were found.. When properly trained, the majority of pts can accurately diagnose AF recurrence and self-inject initial dose of LMWH, what is feasible and may represent an attractive anti-thromboembolic strategy.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Feasibility Studies; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Recurrence; Self Administration; Thromboembolism; Treatment Outcome

Mitral stenosis (MS) in association with atrial fibrillation (AF) is a clinical condition at high risk for systemic thromboembolism. Although oral anticoagulants greatly reduce the incidence of thromboembolism in these patients, the optimal intensity of treatment has never been tested in specific clinical trials, and current recommendations are derived from studies of nonrheumatic AF. In this study we tested the effectiveness of two different intensities. The study design was carried out as an open randomized prospective study in an anticoagulation clinic. We randomized 103 patients with MS and AF to a low (target INR = 2) or moderate (target INR = 3) anticoagulation regimen. The primary end points were systemic thromboembolism, major bleeding and vascular death. During a mean follow-up of 4.5 years, 1 systemic embolism occurred in the low intensity group (0.41 per 100 pt/yrs, CI 0.01-2.3), and 1 minor stroke occurred in the moderate intensity group (0.40 per 100 pt/yrs, CI 0.01-2.3; p = ns). Major bleeding occurred in 8 patients, with 3 in the low intensity (1.25 per 100 pt/yrs) and 5 in the moderate intensity group (2.0 per 100 pt/yrs, Incidence Rate Ratio 0.6, CI 0.1-3.1; p = ns). Total events (systemic embolism, major bleeding and vascular death) occurred in 7 low intensity patients and 8 moderate intensity patients. As expected, minor bleeding was more frequent in the moderate intensity group of patients, who actually had more intense treatment and required closer monitoring of oral anticoagulant treatment. These data suggest that low intensity anticoagulation, as performed in an anticoagulation clinic, is effective and safe in high risk patients with MS and AF.

Topics: Acenocoumarol; Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Stenosis; Random Allocation; Thromboembolism; Time Factors; Warfarin

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 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

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

A double-blind randomized trial was conducted to research a hypercoagulable state rebound after abrupt versus gradual withdrawal of acenocoumarol, 20 patients were included: 10 in the abrupt withdrawal group (AW) and 10 in the gradual withdrawal group (GW). Between days 1 and 15,F1 + 2 was higher in group AW (P < 0.002). A significant increase of D-dimer with time was found (P < 0.001) without difference between the two groups, tPA and PAI-1 levels remained stable throughout without difference between the two groups. No rebound phenomenon was observed. Four thrombotic recurrences were observed: group AW: 1, group GW: 3 (P = 0.29). There is neither clinical nor biological support for a gradual anticoagulation withdrawal.

Topics: Acenocoumarol; Blood Coagulation; Double-Blind Method; Female; Fibrinolysis; Humans; Male; Recurrence; Thromboembolism; Time Factors

This study assessed the risk associated with several schedules of perioperative treatment with coumadin in anticoagulated patients who underwent oral surgery.. A prospective, randomized study compared bleeding complications with six perioperative schedules in 92 patients chronically treated with acenocoumarol. In three of the perioperative schedules, the dose was reduced before surgery and calcium heparin was added. In the other three, oral anticoagulation was not modified and heparin was not used. The groups also differed regarding the antifibrinolytic agents used and the postoperative measures applied.. Those schedules in which the oral anticoagulation was not modified preoperatively and an antifibrinolytic agent was applied locally both during and after surgery were not associated with a significantly higher odds ratio of bleeding complications than those in whom oral anticoagulation was reduced and calcium heparin was added preoperatively.. In orally anticoagulated patients who undergo oral surgery, schedules that maintain the oral anticoagulant regimen and use local tranexamic acid as an antifibrinolytic agent postoperatively for 2 days are safe, simple, and less troublesome.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Antifibrinolytic Agents; Chi-Square Distribution; Dental Care for Chronically Ill; Female; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Logistic Models; Male; Mouthwashes; Odds Ratio; Prospective Studies; Thromboembolism; Tooth Extraction; Tranexamic Acid

Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism.. Secondary analysis of a prospective, randomized, assessorblind, multicenter clinical trial.. One university and 2 regional teaching hospitals.. 188 patients treated with heparin or danaparoid for acute venous thromboembolism.. The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively.. Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area < or = 2 m2 (odds ratio 2.3, 95% CI 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% CI 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders.. A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.

Topics: Acenocoumarol; Acute Disease; Adult; Aged; Body Surface Area; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Combinations; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prospective Studies; Risk Factors; Single-Blind Method; Thromboembolism; Thrombolytic Therapy

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aortic Valve; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Germany; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Mitral Valve; Phenprocoumon; Postoperative Complications; Prospective Studies; Survival Rate; Thromboembolism; Warfarin

After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.

Topics: Acenocoumarol; Aspirin; Dipyridamole; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Valve Prosthesis; Humans; Male; Middle Aged; Thromboembolism; Time Factors

202 patients undergoing surgery involving the lower limbs were given antithrombotic treatment for at least 21 days, or until they had regained full mobility. Following subcutaneous prophylaxis with a combination of heparin and dihydroergotamine, two oral regimens were compared in a controlled and randomized prospective study. The first treatment consisted of a combination of acetylsalicylic acid (ASA) and dihydroergotamine (DHE), and the second of acenocoumarol. The radiofibrinogen uptake test was carried out in high-risk patients (i.e. those undergoing hip surgery) to detect deep-vein thrombosis. No statistically significant difference was found between the two groups. However, the ASA/DHE combination enjoyed better patient acceptance and was much easier to use.

Topics: Acenocoumarol; Adult; Aged; Aspirin; Dihydroergotamine; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leg; Male; Middle Aged; Postoperative Complications; Prospective Studies; Random Allocation; Thromboembolism

Topics: Acenocoumarol; Adult; Anticoagulants; Aspirin; Clinical Trials as Topic; Drug Evaluation; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Platelet Aggregation; Thromboembolism

The effect of either heparin-dihydergot or heparin-acenocoumarin on the incidence of deep-vein thrombosis in the legs was studied in 181 women undergoing Ender nailing for intertrochanteric fracture of the femur. All the patients were screened with the 125-I-fibrinogen uptake test, confirmed by a bilateral ascending venogram. Deep-vein thrombosis developed in 40 per cent of the heparin-dihydergot group and in 61 per cent of the heparin-acenocoumarin group (p less than 0.015).

Topics: Acenocoumarol; Aged; Aged, 80 and over; Bone Nails; Dihydroergotamine; Drug Evaluation; Drug Therapy, Combination; Female; Fibrinogen; Heparin; Hip Fractures; Humans; Iodine Radioisotopes; Iothalamate Meglumine; Middle Aged; Radiography; Radionuclide Imaging; Random Allocation; Thromboembolism; Time Factors

Topics: Acenocoumarol; Cesarean Section; Clinical Trials as Topic; Dextrans; Female; Genital Diseases, Female; Humans; Leg; Obstetric Labor Complications; Oxyphenbutazone; Phlebitis; Postoperative Complications; Pregnancy; Pulmonary Embolism; Thromboembolism; Thrombophlebitis

Topics: Acenocoumarol; Adult; Aged; Female; Fracture Fixation; Fractures, Bone; Hip Injuries; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism

Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy is bleeding, and sometimes it can occur in unsuspected areas. Spontaneous pectoral hematoma is one of the rare complications due to over anticoagulation by VKA therapy, with only a few cases reported in the literature. Concomitant use of this therapy with commonly used antibiotic, especially in the elderly with multiple comorbidities, can increase the risk of bleeding. Herein, we report a case of a 72-year-old woman under VKA for the treatment of atrial fibrillation, who presented with a spontaneous massive pectoral hematoma, while using antibiotic to treat a respiratory tract infection, who was successfully managed.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Female; Hematoma; Hemorrhage; Humans; Thromboembolism; Vitamin K

Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen.. To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin.. The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin.. Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191).. The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Chile; Humans; Thromboembolism; Vitamin K

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Antitussive Agents; Cough; Drug Interactions; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Nonprescription Drugs; Noscapine; Phenprocoumon; Thromboembolism

Essentials The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited. We used data from a multicenter retrospective follow-up study in children in the Netherlands. The quality of anticoagulation control in the first month of use was low, but improved thereafter. No thromboembolic events occurred, however bleeding events occurred in 1-3 out of 10 patients.. Background The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study. Patients who used acenocoumarol or phenprocoumon at an age of ≤ 18 years, were selected from four pediatric hospitals and one anticoagulation clinic in the Netherlands. The quality of treatment was assessed by calculating the percentage of time in therapeutic INR range (TTR) for the first month and for every 3 months of use during the first year of treatment. Effectiveness and safety were assessed by the number of thromboembolic and bleeding events. Results In total, 213 patients participated, of whom 187 (155 acenocoumarol; 32 phenprocoumon) were included in this analysis. The mean TTR was 47.0% and 51.4% in the first month of use for acenocoumarol and phenprocoumon, respectively. After the first 3 months the mean TTR for both VKAs was above 64%. In 14.6% (acenocoumarol) and 31.3% (phenprocoumon) of the patients a bleeding event occurred during the first year of treatment; no thromboembolic events were reported. Conclusions The quality of anticoagulation treatment was low during the first month of use and leaves room for improvement. After the first month it increased to an acceptable level. However, bleeding events occurred frequently during the first year.

Topics: Acenocoumarol; Administration, Oral; Adolescent; Age Factors; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Drug Monitoring; Female; Guideline Adherence; Hemorrhage; Humans; Infant; International Normalized Ratio; Male; Netherlands; Phenprocoumon; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality Indicators, Health Care; Retrospective Studies; Thromboembolism; Time Factors; Treatment Outcome

Despite the increasing utilization of direct oral anticoagulant (DOAC) prescriptions, vitamin K antagonists (VKAs) remain the treatment of choice for treating and preventing thromboembolic events. The morbidity and mortality of VKAs are partly due to the difficulty of keeping the patient within the therapeutic range. For patients treated by VKA, time in therapeutic range (TTR) is a quality parameter of treatment, widely used in clinical trials but rarely by prescribers. It is well established that its use correlates with the risk of hemorrhage, thrombosis or mortality. We studied this parameter in a cohort of patients to evaluate the quality of their therapeutic follow-up and tried to identify risk factors for low TTR.. The study was made in collaboration with LaboSud Oc Biologie for a duration of 4 months. It included 3387 patients representing 2,4029 INR. We calculated the patients' TTR. The laboratory transmitted to us the sex and age of each patient and the VKA molecule used, the therapeutic range and the specialty of the prescriber. We then analyzed the odds ratio associated with these different factors.. The mean TTR was 68%, close to the TTR recommended by scientific societies. Patient's sex was the only statistically correlated factor, with a worse equilibrium in females taking VKAs (OR=1.22, 95% CI: 1.06-1.39, P=0.00552). Many factors usually correlated with poor equilibrium under VKA have not been studied due to lack of information.. Given the context of economic restriction and the TTR of our cohort close to the recommended 70%, there would be no benefit in terms of safety to prefer DOAC for the patients involved in this study. Regular monitoring of the individual patient's as well as the cohort's TTR should optimize the management of patients receiving VKAs.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenindione; Risk Factors; Sex Factors; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world. An appropriate management of treated patients is crucial for their efficacy and safety. The prospective, observational, multicenter, inception-cohort FCSA-START Register, a branch of START Register (NCT02219984) included VKA-treated patients managed by centers of Italian Federation of anticoagulation clinics (AC). Baseline patient characteristics and data during treatment were analyzed and compared with those of ISCOAT study, performed by the Federation and published in 1996/7. 5707 naïve patients [53% males, mean age 73.0 years (28.1% >80 years)], 61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism were included. During the 8906 patient-years (pt-yrs) of observation, 123 patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non-major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more frequent in elderly (≥70 years; p = 0.04), and during initial 3-month therapy (p = 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results <3.0, increasing to 12.5% for INR ≥ 4.5. Thrombotic events were 47 (0.53% pt-yrs; 4 fatal 0.04% pt-yrs). Compared with ISCOAT-1996/7 results, patients older than 80 y are increased from 8 to 28% (p < 0.01), and those treated for AF are increased from 17 to 61%. The quality of anticoagulation control and incidence of MB are not different. However, thrombotic complications fell drastically from 3.5 to 0.53% pt-yrs (p < 0.01), with lower mortality (p = 0.01). VKA-treated patients monitored in Italian AC have good clinical results, with low bleeding and thrombotic complications rates. Important changes in the treated population and improvement in thrombotic complications are detected compared with the ISCOAT-1996/7 study.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Female; Heart Valve Prosthesis; Hemorrhage; History, 20th Century; History, 21st Century; Humans; Incidence; Italy; Male; Middle Aged; Population Groups; Registries; Risk Factors; Thromboembolism; Vitamin K; Warfarin

Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation.. Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol.. We enrolled 474 patients (mean age, 58 years; 68.4% male) undergoing AF catheter ablation between June 2013 and December 2016. All patients were equally assigned to take acenocoumarol (group 1, 136 patients) or DOACs (group 2, 338 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups.. Our analysis showed no significant difference in major and minor complications between the 2 patient groups. Specifically, 3 of 136 patients (2.2%) using uninterrupted acenocoumarol had a major complication (1 patient [0.7%] had transient ischemic attack resolved 8 hours later, 1 [0.7%] had pericardial tamponade, and 1 [0.7%] had a subcapsular renal hematoma) and 2 patients (1.4%) had minor complications (1 [0.7%] pseudoaneurysm and 1 [0.7%] groin hematoma). In group 2, 1 of 338 patients (0.3%) had a major complication (transient ischemic attack). In the same group, 7 patients (2.1%) had a minor complication (1 patient [0.3%] presented with pseudoaneurysm, 4 [1.2%] with pericardial effusion <1 cm, 1 [0.3%] femoral arteriovenous fistula between the femoral artery and femoral vein, and 1 [0.7%] groin hematoma).. DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Registries; Risk Factors; Rivaroxaban; Thromboembolism; Time Factors; Treatment Outcome

Anti-phospholipid syndrome (APLS) is a condition characterized by the presence of raised plasma levels of anti-phospholipid antibodies associated with thrombo-embolic disease and/or poor obstetrical outcomes in women. The epidemiology of APLS is unknown in most sub-Saharan African countries due to limited access to diagnosis tools. We report the case of APLS in a 29-year-old obese woman that was preceded by pre-eclampsia and fetal death. The diagnosis of APLS was made during a thrombo-embolic episode 4 years after the poor obstetrical outcome. Her management was challenging, as she had three thrombo-embolic events within 18-months despite treatment with anti-coagulant (acenocoumarol).. This case highlights the need for screening for APLS after an episode of hypertensive disease in pregnancy or fetal death, and the challenges faced with the treatment, such as resistance to antivitamin K anti-coagulants and the desire for maternity.

Topics: Acenocoumarol; Adult; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Cameroon; Disease Management; Female; Fetal Death; Fetus; Humans; Obesity; Pre-Eclampsia; Pregnancy; Thromboembolism

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Electric Countershock; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Assessment; Risk Factors; ROC Curve; Severity of Illness Index; Spain; Stroke; Thromboembolism

After elective aortic valve replacement, patients are at risk of developing valve thrombosis and systemic arterial thromboembolism. Current guidelines recommend antithrombotic therapy with aspirin or vitamin K antagonists (VKAs) during the first 3 months after the procedure, but have level 2 or 3 evidence. As a consequence, the most appropriate antithrombotic therapy is still a matter of debate. This retrospective study analysed all thromboembolic and bleeding complications in patients with either antiplatelet or anticoagulation therapy 1 year after bioprosthetic aortic valve replacement.. A total of 402 patients undergoing bioprosthetic aortic valve implantation at the VU University Medical Centre and subsequently treated at three regional hospitals were included. The individual duration of either VKAs (acenocoumarol) or aspirin was determined and related to thrombotic and bleeding events. Patients were followed and censored at 1 year postoperatively for survival, cerebral ischaemia, myocardial infarction, peripheral arterial embolism, and minor and major haemorrhages.. A total of 24 thromboembolic complications and 31 bleeding episodes occurred. Multivariable analyses revealed that acenocoumarol caused more bleeding episodes (risk ratio [RR]: 8.41, 95% CI: 3.58-19.79) and a similar amount of thromboembolic events (RR: 1.2, 95% CI: 0.47-3.02) compared with aspirin. Prior use of acenocoumarol was found to be a risk factor for thromboembolic events (RR: 3.1, 95% CI: 1.31-7.19). Gender, dyslipidaemia, prior percutaneous coronary intervention, prior use of acenocoumarol and concomitant coronary artery bypass grafting were found to be predictors for bleeding events.. In patients 1 year following bioprosthetic aortic valve replacement, acenocoumarol therapy was associated with a significant increased risk of bleeding events and no reduction in thromboembolic events compared with antiplatelet therapy. These findings support the recommendations of aspirin over VKAs as postoperative thromboprophylaxis.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Aortic Valve; Aspirin; Bioprosthesis; Electrocardiography; Female; Fibrinolytic Agents; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Postoperative Complications; Practice Guidelines as Topic; Retrospective Studies; Thromboembolism

Bridging with low molecular weight heparins (LMWH) is used in patients undergoing invasive procedures that require interruption of vitamin K antagonists (VKA). Little is known on the mechanisms underlying observed thrombotic and bleeding events. In this exploratory study we investigated the interactive effects of the co-administration of VKA, LMWH and surgery on coagulation.. Blood was sampled daily from day -3 to day +5 in 13 patients. In addition to measurement of INR, anti-Xa activity, thrombin generation (TG) testing and assessment of its protein determinants was performed.. At the time of intervention the mean INR was 1.0 (SD 0.1, range 0.9-1.2); the mean residual anti-Xa level was 0.19 units/ml (SD 0.20 units/ml, range<0.05-0.60). The intervention caused a 2-3 fold increase in TG at day 0. Factor (F) XI had the strongest correlation with TG (peak and endogenous thrombin potential (ETP)) (r=0.6; p=0.02). Thrombomodulin-induced reduction of ETP increased from 10.0% (SD 9.2) at day -3 to 18.2% (SD 9.5) at day 0, p=0.02. After surgery, FVIII (175.9%(SD 58.9% to 246.7% (SD 71.4%); p=0.002) and fibrinogen (4.3 g/L (SD 1.1 g/L) to 5.6 g/L (SD 1.7 g/L); p=0.003) were significantly increased.. Residual anti-Xa activity was present in 84.6% of patients at the day of the intervention. Three prothrombotic mechanisms were exposed: FXI dependent TG, reduced activity of the activated protein C pathway and postoperative rises in FVIII and fibrinogen. For the perioperative management the value of TG merits further study.

Topics: Acenocoumarol; Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Factor VIII; Female; Fibrinogen; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Perioperative Care; Surgical Procedures, Operative; Thromboembolism; Vitamin K

Mitral stenosis (MS) is frequently associated with the development of atrial fibrillation (AF) as a consequence of hemodynamic and inflammatory changes in the left atrium. Both conditions predispose to thrombus formation, with frequent involvement of the left atrial appendage (LAA), and consequent increase in the incidence of systemic thromboembolic events. Percutaneous mitral valvuloplasty (PMV) reduces the risk of thromboembolism in patients with significant mitral stenosis. Percutaneous LAA closure is also associated with a reduction in thromboembolic risk in patients with AF, but there are no data regarding the use of this technique in patients with significant mitral valve disease. We report the case of a 57-year-old-woman with significant MS and permanent AF, in New York Heart Association functional class II, who despite adequate oral anticoagulation with acenocoumarol, presented several clinical episodes of systemic thromboembolism in the last four years. It was decided to perform a combined percutaneous procedure, including both PMV and percutaneous LAA closure with the Amplatzer Cardiac Plug device. No significant acute complications occurred and the patient was discharged on indefinite treatment with acenocoumarol associated with aspirin 100 mg/d for three months. After a one-year follow-up, there have been no new embolic episodes or other complications.

Topics: Acenocoumarol; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Surgical Procedures; Combined Modality Therapy; Female; Humans; Middle Aged; Mitral Valve Stenosis; Septal Occluder Device; Thromboembolism; Treatment Outcome

To investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands.. A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing.. Pharmacogenetic dosing increased costs by €33 and quality-adjusted life-years (QALYs) by 0.001. The incremental cost-effectiveness ratios were €28,349 and €24,427 per QALY gained for phenprocoumon and acenocoumarol, respectively. At a willingness-to-pay threshold of €20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be cost effective compared with the clinical dosing algorithm.. Pharmacogenetic dosing improves health only slightly when compared with clinical dosing. However, availability of low-cost genotyping would make it a cost-effective option.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Cost-Benefit Analysis; Coumarins; Drug Costs; Humans; Markov Chains; Middle Aged; Netherlands; Pharmacogenetics; Phenprocoumon; Quality-Adjusted Life Years; Thromboembolism

Acenocoumarol is a vitamin K antagonist used in some European countries. As warfarin, this drug is characterized by a narrow therapeutic index and a large interindividual variability.. The objective of this study was to assess the involvement of ABCB1 polymorphisms on acenocoumarol treatment.. An observational cohort study was conducted to assess whether there is an association between the presence of the allelic variants of the ABCB1 gene coding for P-glycoprotein and acenocoumarol stabilization and daily doses during the first 35 days of treatment.. One hundred and fifteen patients met the inclusion criteria. The results of the clinical study showed that carriers of ABCB1 c.3435TT were more rapidly stabilized than wild-type patients (HR: 2.97, 95% CI: 1.23-7.18; p = 0.02). The same tendency was observed for the ABCB1 c.2677GT and 2677TT genotypes compared with ABCB1 c.2677GG. The ABCB1 c.2677TT genotype was also associated with a significant increase in doses of acenocoumarol (p = 0.03), the same tendency was observed with the ABCB1 c.3435TT genotype compared with the wild-type patients.. These data suggest that ABCB1 polymorphisms could be involved in the response to acenocoumarol treatment.

Topics: Acenocoumarol; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Genetic; Prospective Studies; Thromboembolism; Treatment Outcome; Vitamin K

The anticoagulant therapy with acenocoumarol is generally associated with a high risk of bleeding and thromboembolic events.. We applied eight already existing acenocoumarol dosing algorithms to Bulgarian patients with low acenocoumarol dose requirements and investigated which of these algorithms would predict most precisely the dose anticoagulant.. Two patients with Bulgarian origin were referred to the outpatient clinical laboratory of "St. Ekaterina" University Hospital for Cardiovascular Surgery and Cardiology, Sofia, Bulgaria. After obtaining written informed consent, both patients were genotyped for polymorphisms in genes for Cytochrome P450 2C9 (CYP2C9), Vitamin K epoxide reductase (VKORC1), Apolipoprotein E (APOE), and Cytochrome P450 4F2 (CYP4F2).. All applied acenocoumarol dosing algorithms predicted relatively similar doses of coumarin anticoagulant in both patients. However, van Schie et al.'s algorithm allowed more accurate calculation of the optimal dose in our patients with extremely low acenocoumarol requirements. Genotyping of selected polymorphic variants in CYP2C9 and VKORC1 showed that both patients were compound heterozygotes for CYP2C9 (CYP2C9*2/*3) and homozygotes for both variants in VKORC1 (VKORC1 1173 T/T, and VKORC1-1639 A/A). This combination of genotypes suggested high sensitivity to acenocoumarol leading to the low anticoagulant dose requirements (0.25 and 1 mg/day, respectively) needed to reach the target International Normalized Ratio of 2.5-3.5.. The genotyping of polymorphic variants in VKORC1 and CYP2C9, together with clinical and demographic parameters, can serve for more precise definition of the individual starting and maintenance doses of coumarin derivatives in each patient.

Topics: Acenocoumarol; Algorithms; Anticoagulants; Aortic Valve; Bulgaria; Coumarins; Dose-Response Relationship, Drug; Female; Genotype; Humans; Male; Middle Aged; Mitral Valve; Pharmacogenetics; Polymorphism, Single Nucleotide; Thromboembolism

Topics: Acenocoumarol; Aged; Anticoagulants; Cross-Sectional Studies; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Randomized Controlled Trials as Topic; Residence Characteristics; Spain; Thromboembolism; Warfarin

Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions.. We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013.. Of 17,410 participants, 6705 switched to a NOAC (switchers) and 10,705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67-82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8.1 months (IQR 3.9-14.0). After a median follow-up of 10.0 months (IQR 9.8-10.0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0.54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0.87; 95% CI 0.67-1.13, p=0.30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0.78, 95% CI 0.54-1.09, p=0.15), switchers from a vitamin K antagonist to rivaroxaban (HR 1.04, 95% CI 0.68-1.58, p=0.86), and non-switchers.. In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed.. None.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Phenindione; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin

For patients who survive intracerebral haemorrhage (ICH) during treatment with oral anticoagulation (OAC), the balance between the benefits and risks of restarting OAC is unclear. The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved. We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH.. We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period. Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through questionnaires and patient files. The primary outcome was recurrent fatal or non-fatal stroke. Secondary outcomes were the occurrence of other haemorrhagic, thrombotic or thromboembolic events. With patients without antithrombotic treatment as reference, we calculated incidence ratios with corresponding 95% confidence intervals (CI) for treatment with OAC and for treatment with antiplatelet therapy.. We included 38 patients, of whom 21 (55%) died during a mean follow-up of 3.5 years. The medication regime changed frequently during follow-up, illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time. Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication, 7 during 63.8 patient-years on antiplatelet medication (incidence ratio 1.9; 95% CI, 0.4-9.4), and 3 during 19.5 patient-years on OAC (incidence ratio 2.7; 95% CI, 0.5-16.3). There was only 1 recurrent ICH, which occurred during treatment with OAC.. In this observational study, no significant difference in the primary outcome measure was found between the treatment groups, but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy. However, based on these results it is difficult to draw any concrete conclusions or make any strong recommendations. A randomized trial to assess the optimal long-term strategy after OAC-related ICH is warranted. Based on the point estimates of our study, such a trial should involve at least 300 patient-years of follow-up.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Retrospective Studies; Risk Factors; Stroke; Surveys and Questionnaires; Survival Analysis; Thromboembolism; Treatment Outcome

Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetics determinants involved in the metabolism of acenocoumarol have been shown to influence the anticoagulant dosage. The aim of this work was to evaluate, for the first time in Maghreb, the allelic frequencies of CYP2C9*2, CYP2C9*3 and VKORC1 -1639G>A mutations, and to establish the role of this polymorphisms in modulating the acenocoumarol requirement in Moroccan patients receiving anticoagulation treatment. Three groups of patients, with low, medium, or high acenocoumarol dose requirements were studied. Genetic analyses of VKORC1 -1639G>A, CYP2C9*2, and CYP2C9*3, were performed in 114 Moroccan patients with stable acenocoumarol dose. The results showed that the allelic frequencies of the three mutations studied was varies, most of patients having CYP2C9*2 and CYP2C9*3 mutations belong to a group with low dose of acenocoumarol, with P-value of 0.0082 and the single patient with CYP2C9*3 on homozygous form belongs to the same group and carried the A allele for VKORC1 gene. In conclusion, the present study confirmed the large interindividual variability in acenocoumarol maintenance dose due to CYP2C9*2, CYP2C9*3 and VKORC1 -1639G>A polymorphisms, and demonstrated that these alleles modulates sensitivity to acenocoumarol, a finding indicating that a reduced initial loading dose of acenocoumarol should be used in carriers of this allele, also, she indicates the usefulness of predictive testing concerning these mutations when an hypocoagulability is installed and not explained by the dose of VKA.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Resistance; Female; Gene Frequency; Humans; Male; Middle Aged; Morocco; Polymorphism, Single Nucleotide; Thromboembolism; Vitamin K Epoxide Reductases; Young Adult

Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetic, clinical and demographic factors have been shown to influence the anticoagulant dosage. Our aim was to investigate the contribution of genetic and non-genetic factors to variability in response to acenocoumarol in Moroccan patients.. Our study included 114 adult Moroccan patients, receiving long-term acenocoumarol therapy for various indications. Tests for VKORC1 -1639G>A promoter polymorphism (rs9923231), CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP4F2 rs2108622 alleles were undertaken using Taq Man(®) Pre-Developed Assay Reagents for allelic discrimination. The statistical analysis was performed using the SAS V9 statistical package.. Genotyping showed that the allele frequencies for the SNPs studied were no different to those found in Caucasians population. A significant association was observed between the weekly maintenance dose and the VKORC1 (P = 0·0027) and CYP2C9 variant genotypes (P = 0·0082). A final multivariate regression model that included the target International Normalized Ratio, VKORC1 and CYP2C9 genotypes explained 36·2% of the overall interindividual variability in acenocoumarol dose requirement.. Our study shows large interindividual variability in acenocoumarol maintenance dose requirement in our population. VKORC1 and CYP2C9 variants significantly affected acenocoumarol dose, in-line with results in other populations. For the Moroccan population, the SNPs that have the largest effect on acecoumarol dose are CYP2C9 rs1799853, CYP2C9 rs1057910 and VKORC1 rs9923231.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cohort Studies; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Female; Genotype; Humans; Male; Middle Aged; Mixed Function Oxygenases; Morocco; Pharmacogenetics; Polymorphism, Single Nucleotide; Prospective Studies; Thromboembolism; Vitamin K Epoxide Reductases; White People; Young Adult

Topics: Acenocoumarol; Adrenal Cortex Function Tests; Adrenal Gland Diseases; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Anticoagulants; Antiphospholipid Syndrome; Female; Fluorodeoxyglucose F18; Hemorrhage; Hemothorax; Hormone Replacement Therapy; Humans; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Thromboembolism

Appropriate dosing of coumarins is difficult to establish, due to significant inter-individual variability in the dose required to obtain stable anticoagulation. Several genetic and other clinical factors have been associated with the coumarins dose, and some pharmacogenetic-guided dosing algorithms for warfarin and acenocoumarol have been developed for mixed populations. We recruited 147 patients with thromboembolic disease who were on stable doses and with an international normalized ratio (INR) between 2 and 3. We ascertained the influence of clinical and genetic variables on the stable acenocoumarol dose by multiple linear regression analysis in a derivation cohort (DC; n = 117) and developed an algorithm for dosing that included clinical factors (age, body mass index and concomitant drugs) and genetic variations of VKORC1, CYP2C9, CYP4F2 and APOE. For purposes of comparison, a model including only clinical data was created. The clinical factors explained 22% of the dose variability, which increased to 60.6% when pharmacogenetic information was included (p<0.001); CYP4F2 and APOE variants explained 4.9% of this variability. The mean absolute error of the predicted acenocoumarol dose (mg/week) obtained with the pharmacogenetic algorithm was 3.63 vs. 5.08 mg/week with the clinical algorithm (95% CI: 0.88 to 2.04). In the testing cohort (n = 30), clinical factors explained a mere 7% of the dose variability, compared to 39% explained by the pharmacogenetic algorithm. Considering a more clinically relevant parameter, the pharmacogenetic algorithm correctly predicted the real stable dose in 59.8% of the cases (DC) vs. only 37.6% predicted by the clinical algorithm (95% CI: 10 to 35). Therefore the number of patients needed to genotype to avoid one over- or under-dosing was estimated to be 5.

Topics: Acenocoumarol; Aged; Algorithms; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Male; Models, Biological; Pharmacogenetics; Spain; Thromboembolism

The study included 52 patients at a high risk of thromboembolic complications, with permanent atrial fibrillation. All patients were treated with acenocoumarol for 6 months and the incidence of hemorrhages was evaluated in all of them. All patients were genotyped by CYP2C9 and VKORC1. The presence of CYP2C9*2 and CYP2C9*3 alleles of CYP2C9 locus and AA genotype of VCORC1 gene polymorphic G-1639(3673)A marker was not associated with the development of hemorrhages under conditions of acenocoumarol treatment (p=0.144 for CYP2C9, p=0.809 and 0.918 for VCORC1 in the total group and subgroup of patients with CYP2C9*1/*1 genotype, respectively). The search for other genetic markers of acenocoumarol efficiency and safety is needed for predicting the risk of hemorrhages during this treatment.

Topics: Acenocoumarol; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Genetic Loci; Genotype; Genotyping Techniques; Hemorrhage; Humans; International Normalized Ratio; Mixed Function Oxygenases; Polymorphism, Genetic; Retrospective Studies; Risk; Russia; Thromboembolism; Vitamin K Epoxide Reductases

Topics: Acenocoumarol; Anticoagulants; Benzamides; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thromboembolism; Thrombosis; Warfarin

The aim of the study is to present our own perioperative bridging therapy with low molecular weight heparin (LMWH) for surgical patients with thrombophilia on long-term acenokumarol therapy [oral anticoagulant (OAC)]. In some European countries, the drug used in secondary antithrombotic prophylaxis is acenokumarol. Forty-two patients with inherited thrombophilia and 21 with antiphospholipid syndrome underwent surgery. All patients were on long-term OAC. This OAC was interrupted 2 days before elective surgery and since that day half of the individual therapeutic dose of LMWH was administered. On day of surgery, the LMWH therapeutic dose was divided into two parts. Starting with day 2 after surgery, the patient was again given half of the individual dose of LMWH every 24 h. On day 4, OAC was additionally included. Both drugs were administered until stabilization of international normalized ratio (INR) values within the therapeutic target for 2 consecutive days. LMWH was then interrupted, whereas OAC continued. No symptoms or episodes of venous thromboembolism were observed. No intraoperative or postoperative hemorrhagic complications were reported. The results suggest that our perioperative bridging therapy is safe and effective for prevention of thromboembolic and hemorrhagic complications.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism

Vitamin K antagonists (VKA) are effective in primary and secondary prevention of thromboembolism, but the associated risk of bleeding is an important limitation. The majority of bleeds are clinically mild. In this study, we assessed whether these minor bleeds are associated with major bleeding, when controlling for other important risk indicators, including the achieved quality of anticoagulation. For this, 5898 patients attending a specialized anticoagulation clinic were retrospectively studied for 1 year after initiation of VKA therapy. The risk of major bleeding was estimated using a multivariate piecewise exponential model with time-varying exposure for occurring minor bleeds. In patients with a minor bleed (N=1015) subsequent major bleeding occurred more frequently than in patients without a minor bleed (N=4883), with an incidence rate of 2·3 [95% confidence interval (CI) 1·4-3·7] vs. 1·2 per 100 person-years (95% CI 0·9-1·7). The adjusted relative risk of subsequent major bleeding after a minor bleed was 2·9 (95% CI 1·1-7·2, P =0·024). The percentage of time that a patient had an International Normalized Ratio (INR) above 5 was also independently associated with major bleeding, with a 2·2-fold increased risk in patients with at least 9% of time above INR 5 (95% CI 1·3-4·0, P=0·006). Minor bleeds alert for subsequent major bleeding, independent of the quality of anticoagulation.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Epidemiologic Methods; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prognosis; Recurrence; Thromboembolism; Vitamin K

The study included 25 patients at high risk of thromboembolic complications. All of them were treated with acenocoumarol for 6 months under control of the frequency of hemorrhage and episodes of severe hypocoagulation (a more than 3-fold rise in INR). All the patients underwent CYP2C9 and VKORC1 genotyping. It was shown that the presence of CYP2C9*2 and CYP2C9*3 alleles in the CYP2C9 locus and the AA genotype of the polymorphous G-1639(3673)A marker of the VKORC1 gene was not associated with the development of severe hypocoagulation episodes (p = 0.261--for CYP2C9, p = 0.616 and 0.361 for VKORC1 in the total group and a subgroup of patients having the CYP2C9*1/*1 genotype respectively and treated with acenocoumarol. The search for other genetic markers of efficacy and safety of this drug should be continued.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cohort Studies; Cytochrome P-450 CYP2C9; Female; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Genetic; Russia; Thromboembolism; Vitamin K Epoxide Reductases

To evaluate the feasibility of designing a randomized controlled study whether open carpal tunnel release (OCTR) surgery can be performed safely under systemic anticoagulant therapy using acetylsalicylacid (ASA) or acenocoumarol (ACM), this preliminary, observational study was performed.. Prospectively, during 1 year, data were collected from all patients who underwent conventional OCTR at the neurosurgical department of the Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. Patients continued anticoagulant treatment perioperatively.. A total of 364 patients were operated on, of whom 45 continued ASA and seven ACM treatment. Only one patient using ASA complained of a postoperative subcutaneous hemorrhage. In the control group without anticoagulants, none of the patients had a bleeding postoperatively.. Continuation of anticoagulant treatment is safe for OCTR. The adverse effects of stopping treatment for surgery can be severe. As a result of this study, we have changed our surgery protocol for OCTR and continue anticoagulant treatment perioperatively.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aspirin; Carpal Tunnel Syndrome; Clinical Protocols; Clinical Trials as Topic; Humans; Neurosurgical Procedures; Outcome Assessment, Health Care; Perioperative Care; Pilot Projects; Postoperative Hemorrhage; Prospective Studies; Risk Assessment; Thromboembolism

Patients with mechanical heart valve prostheses are obligated to receive lifelong oral anticoagulant therapy to prevent thromboembolic complications; however, this treatment is associated with an increased risk of bleeding. The aim of this study was to evaluate the frequency of major hemorrhagic and thromboembolic complications in patients with mechanical heart valves who received oral anticoagulant therapy.. The analysis involved 225 patients who underwent successful surgery in 2000; the mean (+/-SD) follow-up period was 43.3 +/- 9.2 months. Aortic, mitral, and double valve replacement was performed in 128 (56.7%), 70 (31.1%), and 27 (12.1%) of the patients, respectively. There were 128 men (57.3%), and the mean patient age was 57.9 +/- 18.8 years. The following data were assessed: rate of major hemorrhagic and thromboembolic complications, frequency of international normalized ratio (INR) rate measurements, and percentage of results within the therapeutic range.. Major hemorrhagic and thromboembolic complications occurred in 25 patients (11.1%). Seventeen patients (7.5%) survived, and 8 (3.6%) died of the complications. Major hemorrhagic and thromboembolic complications occurred in 17 patients (7.6%) and 8 patients (3.6%), respectively. The mean time between sequential measurements was 4.3 +/- 3.0 weeks, and of all the INR values collected, 42.4% were within, 31.3% were below, and 26.3% were above the target ranges.. Patients with a mechanical heart valve prosthesis receiving acenocoumarol are susceptible to major hemorrhagic and thromboembolic complications, some of which lead to death. Despite the danger related to these complications, patients receiving anticoagulant therapy still have difficulty achieving INR values within the therapeutic range.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Risk Factors; Survival Rate; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Hemorrhage; Humans; International Normalized Ratio; Phenprocoumon; Risk Factors; Thromboembolism; Time Factors

Subtherapeutic anticoagulation levels increase both the risk and severity of thromboembolism. The aim of this study was to determine the cumulative incidence of subtherapeutic international normalised ratios (INRs) and to identify risk factors associated with a low INR. We performed a cohort study in 7,419 patients from a Dutch anticoagulation clinic. Patients who started a first treatment with oral anticoagulants between January 2000 and December 2005 and who were stably anticoagulated (4 consecutive INRs in the therapeutic range) were included. Within the cohort a nested case control study was performed to identify risk factors of subtherapeutic INRs and to determine how often a subtherapeutic INR is the result of medical interference in case of invasive procedures, hospital admissions, haemorrhage or overanticoagulation. In patients with a stable anticoagulation, the median time to a first low INR was 40 weeks. A subtherapeutic INR occurred twice as often in patients using acenocoumarol as in those using phenprocoumon (hazard ratio [HR] 2.1, 95% confidence interval [95%CI]:2.0 - 2.3) and was more common in patients with a high therapeutic range compared to a low therapeutic range (HR 1.8, 95%CI:1.5 - 2.2). Occurrence of a low INR also depended on indication for anticoagulant therapy, with the highest risk in patients who used anticoagulants as prophylaxis and the lowest risk in patients with mechanical heart valves. In 30% of cases the subtherapeutic INR was preceded by an event necessitating vitamin K or discontinuation of the anticoagulant drug.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Risk Factors; Thromboembolism; Time Factors

Unstable oral anticoagulation increases the risk of thrombotic events and bleedings. Acenocoumarol use has been reported to be associated with two-fold higher risk for instability of anticoagulation control compared to warfarin administration.. The aim of the study was to evaluate the effect of introducing warfarin on anticoagulation control in patients with a variable response to acenocoumarol.. Sixty-eight subjects treated with acenocoumarol for 5 months or more and displaying intraindividual variability of international normalized ratio (INR) results were switched to warfarin. Unstable anticoagulation was defined as a failure to achieve a target INR within the preceding 3 months, i.e. > or = 50% of 8 or more INR values below 2 or above 3.5. Patients with stable anticoagulation (<20% of out-of-range INRs), matched for age, gender, and anticoagulation indications, served as a reference group.. Patients with unstable anticoagulation on acenocoumarol had higher body mass index (p<0.01) and serum C-reactive protein levels (p<0.01) compared to stable counterparts. The transition factor between acenocoumarol and warfarin was 1.8 (95% CI 1.69-1.96). The percentage time within the target INR range in patients with unstable anticoagulation was 40.2% at baseline and increased to 60.4% following 6 months on warfarin therapy (p<0.05). The number of subjects with <20% of out-of-range INRs among individuals switched from acenocoumarol to warfarin was 22 (32.4%) vs. 63 (92.6%) in patients on stable anticoagulation after 6 months of follow-up (p<0.001).. Switching acenocoumarol to warfarin in patients with unstable anticoagulation can improve anticoagulation control.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Reproducibility of Results; Thromboembolism; Treatment Outcome; Warfarin

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Salicylates; Thromboembolism; Treatment Outcome; Warfarin

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Monitoring, Physiologic; Patient Compliance; Patient Dropouts; Patient Education as Topic; Risk Factors; Self Care; Thromboembolism; Treatment Outcome

Thromboembolic complications (cerebral infarction and system embolism) are the most threatening ones in patients with ciliary arrhythmia without valvular lesions. Transoesofhageal echocardiography is the method of choice in detection of left atrial auricle thrombosis, which is the main source of thromboembolism in this category of patients. Primary and secondary prevention of thromboembolic complications in patients with ciliary arrhythmia is a topical problem, still remaining unsolved. Administration of indirect anticoagulants, which are the preparations of choice, demands strict doctor's supervision and continuous laboratory monitoring. The study presents authors' own data, based upon the observation of patients treated with either warfarin or acenocumarol. The paper demonstrates equal efficiency of both cumarine anticoagulants. The frequency of haemorrhagic complications after 12-month therapy with either warfarin or acenocumorol in patients with ciliary arrhythmia without valvular lesions was comparable. Warfarin provided more stable level of anticoagulation and thus long-term warfarin therapy was characterized by lower risk of complication.

Topics: Acenocoumarol; Adult; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Primary Prevention; Prospective Studies; Risk Factors; Thromboembolism; Time Factors; 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; Administration, Oral; Anticoagulants; Humans; Monitoring, Physiologic; Research Design; Self Care; Thromboembolism; Time Factors

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

To evaluate the incidence of thromboembolic and haemorrhagic events in a cohort of patients with mechanical heart valves who had to withhold acenocumarol and were treated with enoxaparin.. Observational prospective study.. In hospital; after discharge, and follow up by telephone call.. All consecutive patients with mechanical heart valves admitted to the authors' hospital between May 1999 and January 2002 who had to interrupt treatment with acenocumarol and were treated with enoxaparin as an alternative to other methods were enrolled. In each patient, the following characteristics were prospectively determined: the reason for interrupting acenocumarol, demographic data, estimated global risk for thromboembolic events, international normalised ratio before starting enoxaparin treatment, number of days taking enoxaparin, and mean level of anti-Xa activity during treatment. All patients were followed up through clinical history during the hospitalisation and by telephone after discharge to detect thromboembolic events.. Presence of thromboembolic or haemorrhagic events.. 82 patients were identified and followed up for a mean of 2.8 months (range 1.5-3.5 months) after discharge. 61 of them (74%) had one or more associated thromboembolic risk factors. Acenocumarol was interrupted (to perform an invasive procedure in 74 patients and because of haemorrhagic complication in 8) an average of 11.2 days (range 3-40 days). Most patients received the standard enoxaparin dose (1 mg/kg at 12 hour intervals). Mean (SD) anti-Xa activity was 0.58 (0.3) IU/ml (median 0.51). There were 8 minor and 1 major bleeding events during enoxaparin treatment. No thromboembolic complications were clinically detected during hospitalisation or during follow up (95% confidence interval 0% to 3.6%).. Enoxaparin may be an effective and relatively safe substitute anticoagulant for patients with mechanical heart valves who must withhold acenocumarol.

Topics: Acenocoumarol; Anticoagulants; Blood Loss, Surgical; Cohort Studies; Contraindications; Enoxaparin; Factor Xa; Female; Heart Valve Prosthesis; Hemorrhage; Hospitalization; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Risk Factors; Thromboembolism; Withholding Treatment

To determine guidelines for administering and monitoring acenocoumarol therapy in children, 93 patients (median 5.1 years, range: 0.2-18 years) were prospectively evaluated over a 33-month period. The loading doses used were: <1 year, 0.20 mg x kg-1; >1-5 years, 0.09 mg x kg-1; 6-10 years, 0.07 mg x kg-1; 11-18 years, 0.06 mg x kg-1. In this study, the loading dose and the dose to achieve and maintain target therapeutic range (TTR) for acenocoumarol are age-dependent, with infants having the highest and teenagers having the lowest requirements. The use of a different loading dose according to age has allowed most of the children (80%) in all the age groups to achieve TTR in less than 1 week. No patients had serious bleeding or thrombotic complications. We conclude that there is an age-dependent response to acenocoumarol in pediatric patients. The implementation of an age-adjusted loading dose regimen reduces the length of hospitalization required to achieve effective anticoagulant therapy.

Topics: Acenocoumarol; Adolescent; Age Factors; Anticoagulants; Child; Child, Preschool; Female; Humans; Infant; Male; Thromboembolism; Treatment Outcome; Vascular Diseases

Topics: Acenocoumarol; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Gene Frequency; Genotype; Humans; Italy; Polymerase Chain Reaction; Thromboembolism; Warfarin

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

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aortic Aneurysm; Brain Ischemia; Cyanosis; Heparin; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Infarction; Risk Factors; Thromboembolism; Thrombosis; Toes; Urinary Bladder Neoplasms

Self-testing and self-monitoring with portable prothrombin time (PT) monitors has been shown to be feasible and safe. However the ability of patients on chronic oral anticoagulant therapy (OAT) to self-adjust their dose without specific training has never been properly evaluated. The aims of this study were to evaluate: 1) the ability of patients on chronic OAT to self-adjust their dose without specific training; 2) the integration of a portable PT monitor (Coagucheck, Roche Diagnostics, Germany) for home use into routine patient care in anticoagulation clinics.. A nested case-control study was conducted in four centers of the Italian Federation of Anticoagulation Clinics (FCSA). Patients (n=78) on stable OAT for at least 6 months (cases: 47 men, 31 women, age range: 18-75 years) were enrolled on a volunteer basis after passing an Abbreviated Mental Test and providing informed consent. After three instruction sessions on the use of Coaguchek, subjects performed the PT test at home, communicated the INR results to the Center and suggested the dose adjustment and date for next control as they thought appropriate. However, they were requested to follow the prescription made by the Center. Controls (78 subjects) matched by age (+/- 5 years), sex and therapeutic range with the cases, were selected from among those who attended the anticoagulation clinics and managed by usual care.. When compared with the dose prescribed by the Clinic, the dose suggested by warfarin and acenocoumarol users was equal to or within +/- 6% of the mean weekly dose in 80% and 82% of suggestions, respectively. Time spent in the therapeutic range during the study was the same (80%) for cases and controls.. Selected patients on chronic anticoagulant therapy can acquire a satisfactory ability for self-adjustment of OAT dose without specific training.

Topics: Acenocoumarol; Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Female; Hemorrhage; Humans; International Normalized Ratio; Italy; Male; Middle Aged; Outcome Assessment, Health Care; Patient Acceptance of Health Care; Patient Compliance; Prothrombin Time; Random Allocation; Self Administration; Self Care; Surveys and Questionnaires; Thromboembolism; Warfarin

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Drug Antagonism; Humans; Thromboembolism; Ticlopidine

Topics: Acenocoumarol; Aged; Anti-Bacterial Agents; Anticoagulants; Clarithromycin; Drug Interactions; Female; Humans; Thromboembolism

The optimal intensity of oral anticoagulant therapy for patients with mechanical heart valves (i.e., the level at which thromboembolic complications are effectively prevented without excessive bleeding) is not known. We attempted to determine the optimal intensity by calculating the incidence of both complications at different levels of anticoagulation.. Data were collected on all patients with mechanical heart valves who have been seen at four regional Dutch anticoagulation clinics since 1985. The primary outcome events were episodes of thromboembolism or major bleeding. The intensity-specific incidence of each type of event was calculated as the number of events that occurred at a certain intensity of anticoagulation (expressed in terms of the international normalized ratio [INR]) divided by the number of patient-years during which the INR was at this level in the total patient population.. A total of 1608 patients were followed during 6475 patient-years. Cerebral embolism occurred in 43 patients (0.68 per 100 patient-years) and peripheral embolism in 2 (0.03 per 100 patient-years). Intracranial and spinal bleeding occurred in 36 patients (0.57 per 100 patient-years) and major extracranial bleeding in 128 (2.1 per 100 patient-years). The optimal intensity of anticoagulation, at which the incidence of both complications was lowest, was achieved when the INR was between 2.5 and 4.9.. The intensity of anticoagulant therapy for patients with prosthetic heart valves is optimal when the INR is between 2.5 and 4.9. To achieve this level of anticoagulation, a target INR of 3.0 to 4.0 is recommended.

Topics: Acenocoumarol; Aged; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heart Valve Prosthesis; Hemorrhage; Humans; Incidence; Male; Middle Aged; Phenprocoumon; Prothrombin Time; Thromboembolism

The outcome of 50 surgical procedures in 41 patients who were anticoagulated at the time of surgery were reviewed to determine whether anticoagulation was associated with an increase in ophthalmic morbidity. Twenty-seven patients were receiving warfarin and 14 patients nicoumalone. The International Normalised Ratio (INR) was determined immediately prior to surgery and ranged from 1.1 to 4.9. Thirty-nine operations were performed under local anaesthetic and 11 under general anaesthetic. Thirty-three patients had extracapsular cataract extractions with posterior chamber lens implantation. No major haemorrhagic complications were associated with the local anaesthetic or the surgical procedure. Patients on anticoagulation therapy are at risk of life-threatening complications if their anticoagulation is stopped or reduced. This study demonstrates that most ophthalmic surgical procedures can be safely performed whilst the patient is therapeutically anticoagulated.

Topics: Acenocoumarol; Anticoagulants; Blood Loss, Surgical; Eye Diseases; Humans; Intraoperative Care; Prospective Studies; Thromboembolism; Warfarin

The aim of this study was to investigate the factors related to the presence of left atrial spontaneous echo contrast in mitral valve disease, and to ascertain whether it is a predictor of thromboembolism. One hundred and one patients (47 men, 54 women) with a mean age of 57.04 +/- 10.6 years who underwent transthoracic and transesophageal echocardiography were included in the study. Forty-five (44.5%) had isolated or predominant mitral valve stenosis, 12 (11.9%) predominant mitral insufficiency and 44 (43.6%) had had previous mitral valve replacement. Left atrial spontaneous echo contrast was detected by transesophageal echocardiography in 58 patients, while the transthoracic approach detected it in only 15 (14.9%) (P < 0.0001). An atrial thrombus was found in six cases, with a history of recent systemic embolism in three of them. There was no thrombus in the left atria of a further nine patients, despite definitive histories of recent systemic embolism. The finding of left atrial spontaneous echo contrast was related to the presence of atrial fibrillation or enlarged left atrium, the severity of mitral stenosis and the absence of significant mitral insufficiency. Anticoagulant therapy was not significantly associated with spontaneous left atrial echo contrast, but a stepwise linear regression analysis showed that its presence was the only independent predictor of thromboembolism (p < 0.0001). We conclude that left atrial spontaneous echo contrast in mitral valve disease can be discovered mainly by transesophageal echocardiography, and is correlated with factors which are associated with low left atrial blood flow velocity such as atrial fibrillation, enlarged left atrium, mitral stenosis of increased severity and the absence of significant mitral insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acenocoumarol; Adult; Aged; Atrial Fibrillation; Echocardiography; Echocardiography, Doppler; Echocardiography, Transesophageal; Female; Heart Atria; Heart Valve Prosthesis; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Postoperative Complications; Prosthesis Design; Regression Analysis; Risk Factors; Thromboembolism

A selected group of patients who underwent valve replacement were analyzed to evaluate the feasibility, effectiveness and safety of combined treatment with moderate intensity anticoagulation plus aspirin. One hundred ninety-six patients who received a total of 204 mechanical valve prostheses between 1985 and 1991 were selected according to rigid criteria. The prostheses included 124 valves of caged ball design, 62 St. Jude valves and 18 others. The follow up of the whole population was 581.8 patient years, with an average of 2.97 patient years, and was complete by the definition criteria. All patients received moderate intensity anticoagulation with acenocoumarol (target International Normalized Ratio 2.5 to 3.5) and daily aspirin (100 mg or 325 mg). The incidence of thromboembolic events for the whole group was 3.26% per patient year, but only 1.6% in patients "compliant" with treatment. Preoperative embolism and non-compliance with treatment had a strong correlation with postoperative thromboembolism. The INR values had a strong correlation with both thromboembolic and hemorrhagic events. The incidence of serious hemorrhagic events was 4.12% patient years although only two cases (0.34%/pty) were fatal (cerebral hemorrhages). There was no difference in hemorrhagic incidence between patients receiving either 325 mg or 100 mg daily. A low incidence of thromboembolic complications was attained with the use of combined antithrombotic and antiplatelet therapy, even in the first generation caged ball type prostheses. However, the combination of moderate intensity anticoagulation with either 325 mg or 100 mg aspirin was associated with a risk of bleeding similar to high intensity anticoagulation alone. The risk of bleeding appeared to be greater in the presence of gastric pathology, and the combination of anticoagulants and aspirin should be avoided in patients with these conditions.

Topics: Acenocoumarol; Adult; Aged; Aspirin; Blood Coagulation Tests; Dose-Response Relationship, Drug; Drug Therapy, Combination; Feasibility Studies; Female; Follow-Up Studies; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prosthesis Design; Retrospective Studies; Survival Rate; Thromboembolism; Treatment Outcome

One hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined FXII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in FXII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p less than 0.003). In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established. In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history. We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Ambulatory Care; Factor XII Deficiency; Female; Humans; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Prevalence; Recurrence; Risk Factors; Thromboembolism

Topics: Acenocoumarol; Drug Interactions; Humans; Thromboembolism

This report documents our experience with long term antithrombotic therapy (acenocoumarol plus aspirin) in 31 children and adolescents, from 5 months to 16 years of age. The valves replaced were mitral in 20 patients, aortic in 4, mitral-aortic in 4 and tricuspid in 3; the overall follow-up time was of 1336 months. Anticoagulant requirement in each children was not in correlation with age, but a significant increase (p less than 0.01) was found in association with sexual development. Our total incidence of embolic episodes was 1.49/1000 patient-months. The embolic incidence on adequate anticoagulated patients was 0.74/1000 patient-months and 93.7% of all patients were free of thrombo-embolic accidents up to 96 months of follow-up. Minor haemorrhage in relation to an excess of anticoagulant was 1.49/1000 patient-months. There has been only one major bleeding episode associated with severe sepsis, with an incidence of 0.74/1000 patient-months. No major difficulties were found in the management of anticoagulant treatment and its association with antiplatelet drugs in children.

Topics: Acenocoumarol; Adolescent; Age Factors; Aspirin; Child; Child, Preschool; Drug Therapy, Combination; Fibrinolytic Agents; Heart Valve Prosthesis; Hemorrhage; Humans; Postoperative Complications; Sex Factors; Sexual Maturation; Thromboembolism

In an attempt to identify the best treatment for pregnant women with cardiac-valve prostheses who are receiving oral anticoagulants, we studied 72 pregnancies prospectively. In 23 pregnancies (Group I), the coumarin derivative acenocoumarol was discontinued and the patients received 5,000 U of subcutaneous heparin every 12 hours from the 6th to the 12th week of gestation, in 12 pregnancies (Group II), heparin was not substituted for the coumarin derivative until after the 7th week, and in 37 pregnancies, detected after the first trimester (Group III), the coumarin derivative was given throughout gestation. In most patients heparin was again substituted for the oral anticoagulant after the 38th week. Three mothers had thrombosis of a tilting-disk mitral prosthesis (two cases were fatal) during heparin treatment. No differences were found in the rates of spontaneous abortion in the three groups. Coumarin embryopathy occurred in 25 percent and 29.6 percent of the pregnancies in Groups II and III, respectively. We conclude that in the second and third trimesters of pregnancy, coumarin derivatives provide effective protection against thromboembolism while causing few fetopathic effects, but that these agents are contraindicated from the 6th to the 12th weeks of gestation. Low-dose heparin does not protect against prosthetic-valve thrombosis, and the possibility that a larger dose might be more effective requires further exploration.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Acenocoumarol; Adolescent; Adult; Coumarins; Drug Administration Schedule; Female; Fetal Death; Fetus; Heart Valve Prosthesis; Heparin; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Thromboembolism

The Omniscience prosthetic heart valve has been clinically evaluated in 44 patients operated on between January and July, 1981. There were 23 aortic valve replacements (AVR), 18 mitral valve replacements (MVR) and 3 double valve replacements (DVR). Mean age was 48 +/- 11 years. Preoperatively, 61% patients were in New York Heart Association (NYHA) functional class IV, 36% in class III and 2% in class II. The hospital mortality rate was 4.5%. Actuarial freedom from thromboembolic events was 97.4 +/- 2.6% (3 1/2 years of follow-up). Postoperatively, 93% of the patients were in NYHA class I and 7% in class II. There were 7 cases of periprosthetic leak requiring reoperation (6 AVR, 1 MVR) for an overall incidence of 6.3% per patient year. In all these cases the causative factor was considered to be the Dacron sewing ring. All patients survived the reoperation. The actuarial survival rate was 93.9 +/- 5.9% for AVR and 93.7 +/- 6.1% for MVR. These data would suggest that the Omniscience prosthesis represents an acceptable device for heart valve replacement, except for the high incidence of periprosthetic leakage, related to the Dacron sewing ring. Recent modification of the valve-construction including a Teflon sewing ring may avoid the relatively high rates of periprosthetic leakage following implantation of this mechanical valve.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Cardiovascular Diseases; Equipment Design; Equipment Failure; Evaluation Studies as Topic; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Reoperation; Thromboembolism

It is reported on the occurrence of haemorrhagic complications at old age in patients treated with coumarin. Altogether 352 patients were examined, 96 of them were older than 70 years. A small part of the patients, above all men with obliterating vascular occlusions of the lower extremity were additionally given also thrombocyte aggregation inhibitors. The effective prothrombin level was nearly the same in the two, groups, i.e. in the patients younger and older than 70 years. There was no difference in frequency and severity of the haemorrhages with the exception of macrohaematuria which, however, appeared above all in the younger age group and in women older than 70 years. Under observation of the indications and with a regular control a long-term treatment with coumarin preparations can performed without any particular risk also at old age.

Topics: Acenocoumarol; Aged; Arteriosclerosis Obliterans; Cerebral Hemorrhage; Female; Hemorrhage; Humans; Long-Term Care; Male; Prothrombin; Pulmonary Embolism; Thromboembolism; Thrombophlebitis

Topics: Acenocoumarol; Anticoagulants; Female; Heparin; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Risk; Thromboembolism; Thrombosis

To assess the maternal and fetal risks in patients with cardiac valve prostheses, a series of 223 pregnancies in 156 women was studied. In 68 pregnancies (group I) treatment with antiplatelet agents was substituted for that with coumarinics from the first trimester on. Group II (128 pregnancies) received coumarinics through the thirty-eighth week of gestation. Three patients in group I died as a result of thrombosis of their caged-ball valves. The incidence of cerebral embolism was 25.0% in group I and 2.3% in group II patients, while that of spontaneous abortion was 10.3% and 28.1%, respectively. Coumarin embryopathy was found in 7.9% of group II infants. Fetal death did not occur in the 12 cases in which subcutaneous heparin was substituted for the coumarin derivative in the first trimester and the last 2 weeks of pregnancy (group III), but maternal cerebral embolism developed in 8.3% of the patients. Finally, uneventful pregnancies and deliveries were observed in 12 of 15 mothers (group IV) with biological prostheses who received no anticoagulants. It is concluded that (1) women with cardiac valve prostheses should be counseled against becoming pregnant, (2) antiplatelet agents do not provide protection against thromboembolism in these patients, (3) because of the high incidence of fetal death and birth defects use of coumarinics is contraindicated in the first trimester and the last weeks of pregnancy, (4) the substitution of heparin at these times may decrease the incidence of these complications, and (5) bioprostheses are indicated in women who wish to bear children.

Topics: Acenocoumarol; Adolescent; Adult; Anticoagulants; Aortic Valve; Bioprosthesis; Female; Fetal Death; Heart Valve Prosthesis; Humans; Mitral Valve; Pregnancy; Pregnancy Complications; Prothrombin Time; Risk; Thromboembolism; Time Factors; Tricuspid Valve

Topics: Acenocoumarol; Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Arteriosclerosis; Embolism; Factor VII; Factor X; Female; Humans; Kinetics; Male; Middle Aged; Prothrombin; Prothrombin Time; Thromboembolism; Time Factors

Topics: Acenocoumarol; Heparin; Humans; Myocardial Infarction; Thromboembolism

Topics: Acenocoumarol; Drug Therapy, Combination; Heparin; Humans; Myocardial Infarction; Thromboembolism

Topics: Acenocoumarol; Heart Valve Prosthesis; Humans; Postoperative Complications; Thromboembolism

The ADP- and collagen-induced thrombocyte aggregation has been investigated and statistically evaluated in 25 women. These patients had undergone vaginal hysterectomy and colporrhaphy due to descensus vaginae et uteri and received 500 ml Macrodex 6% during the operation and Sintrom from the 1st post-operative day as prophylactic treatment for early and late thromboembolism. After administration of dextran 60, the ability of the thrombocytes to aggregate was reduced by half, 2 hours post-operatively, independent of the concentration and type of agent added in the aggregation test, and remained at this level during the 1st post-operative day. The original values were once again attained on the 4th post-operative day. The speed and force of deaggregation showed reverse behaviour. There was no influence apparent due to age of the patient or phase of the cycle (proliferation, secretion and post-menopausal). By carrying out this combined prophylactic treatment for thromboembolism, satisfactory protection is provided in the dangerous phases during the operation and post-operatively.

Topics: Acenocoumarol; Adenosine Diphosphate; Adult; Dextrans; Female; Humans; Hysterectomy; Menstruation; Platelet Aggregation; Thromboembolism

A comparison of the incidence of thromboembolic (TE) episodes was made in three groups of patient who underwent aortic valve replacement with the cloth-covered Starr-Edwards prostheses. Group 1 consisted of patients who received anticoagulants for either the entire period of follow-up or for a period of variable duration, after which these agents were no longer administered. When anticoagulants were stopped, 22 patients were categorized as Group 3 for study. Group 2 comprised patients who never received anticoagulants. Of the 147 patients followed in Group 1, 14 suffered one episode of TE. Six patients experienced major emboli; 3 of them died. Twenty of the 82 patients followed in Group 2 (no anticoagulants) suffered TE complications. There were 10 episodes of major emboli. Five of the 22 patients in Group 3 suffered an episode (all major) of TE. It is concluded from this study that anticoagulants should be given permanently to all patients with cloth-covered Starr-Edwards prostheses. Indeed, there is no period after operation when the incidence of TE is so low that anticoagulation may be safely discontinued.

Topics: Acenocoumarol; Aortic Valve; Heart Valve Prosthesis; Humans; Thromboembolism; Time Factors; Warfarin

Anticoagulation therapy with acenocoumarin or with anticoagulants plus aspirin was given to 65 and 57 patients, respectively, with cardiac valve replacement. The follow-up was 1,462 months (22.5 months per patient) for the first group and 1,411 months (24.7 months per patient) for the second group. The frequency of embolic accidents was significantly lower in the group taking aspirin: Thirteen thromboembolic accidents were detected in patients receiving the anticoagulant and 3 in the group receiving the anticoagulant plus aspirin. These figures represent a 20.3 per cent incidence (one each 9.3 years of treatment) for the anticoagulant group and a 5.2 per cent incidence (one accident each 39.1 years of treatment) for the other group. The statistical significance between groups is p less than 0.005. There was no difference in the hemorrhagic risk between the two groups. We conclude that the use of an anticoagulant plus aspirin is a good and safe therapy for the prevention of thromboembolism in these patients.

Topics: Acenocoumarol; Anticoagulants; Aspirin; Blindness; Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Humans; Intracranial Embolism and Thrombosis; Male; Myocardial Infarction; Postoperative Complications; Thromboembolism

Topics: Acenocoumarol; Aged; Anticoagulants; Aspirin; Blood Coagulation Disorders; Dextrans; Drug Therapy, Combination; Female; Germany, West; Hemorrhage; Heparin; Humans; Middle Aged; Postoperative Care; Postoperative Complications; Preoperative Care; Pulmonary Embolism; Thromboembolism; Time Factors

Topics: Acenocoumarol; Adult; Blood Coagulation Tests; Cesarean Section; Female; Genital Diseases, Female; Genital Neoplasms, Female; Heparin; Humans; Hysterectomy; Middle Aged; Postoperative Care; Postoperative Complications; Pregnancy; Thromboembolism; Thrombosis

Topics: Acenocoumarol; Adult; Aged; Cesarean Section; Female; Genital Diseases, Female; Humans; Hysterectomy; Middle Aged; Pregnancy; Preoperative Care; Thromboembolism; Thrombosis

Topics: Acenocoumarol; Anticoagulants; Blood Coagulation Disorders; Coumarins; Embolism; Femoral Neck Fractures; Humans; Postoperative Complications; Thromboembolism; Veins

Topics: Acenocoumarol; Aged; Anticoagulants; Ethyl Biscoumacetate; Female; Humans; Male; Middle Aged; Postoperative Complications; Prothrombin; Thromboembolism; Warfarin

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Breast Diseases; Coumarins; Diabetes Complications; Female; Foot Diseases; Hemorrhage; Humans; Intracranial Embolism and Thrombosis; Middle Aged; Necrosis; Obesity; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Thrombosis

Topics: Acenocoumarol; Anticoagulants; Blood Coagulation Tests; Esterases; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Prothrombin; Prothrombin Time; Thromboembolism

Topics: Acenocoumarol; Adult; Aged; Angina Pectoris; Anticoagulants; Coronary Disease; Coumarins; Female; Heart Diseases; Heart Valve Diseases; Heart Valve Prosthesis; Hemorrhage; Humans; Long-Term Care; Male; Middle Aged; Myocardial Infarction; Phenindione; Prothrombin Time; Thromboembolism

Topics: Acenocoumarol; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Thromboembolism

Topics: Acenocoumarol; Female; Germany, West; Humans; Postoperative Complications; Thromboembolism

Topics: Acenocoumarol; Adult; Aged; Female; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism

Topics: Acenocoumarol; Aged; Female; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Chronic Disease; Coronary Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction; Thromboembolism

Topics: Acenocoumarol; Blood Coagulation Tests; Drug Therapy; Humans; Postoperative Care; Postoperative Complications; Prothrombin Time; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Female; Genital Diseases, Female; Gynecologic Surgical Procedures; Humans; Postoperative Care; Surgical Procedures, Operative; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Ascorbic Acid; Dicumarol; Family Practice; General Practice; Occupations; Prothrombin Time; Statistics as Topic; Thromboembolism; Toxicology; Warfarin

Topics: Acenocoumarol; Aged; Anticoagulants; Cerebrovascular Disorders; Coronary Disease; Dicumarol; Drug Therapy; Ethyl Biscoumacetate; Geriatrics; Humans; Incidence; Middle Aged; Mortality; Neoplasm Metastasis; Neoplasms; Pathology; Phenindione; Thromboembolism; Warfarin

Topics: Acenocoumarol; Anticoagulants; Heparin; Humans; Myocardial Infarction; Prothrombin Time; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Biomedical Research; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coronary Disease; Coumarins; Peripheral Vascular Diseases; Thromboembolism; Vascular Diseases

Topics: Acenocoumarol; Anticoagulants; Coumarins; Female; Genitalia; Genitalia, Female; Gynecology; Humans; Obstetric Labor Complications; Obstetrics; Pregnancy; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Phenylbutazone; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Humans; Thromboembolism

Topics: 4-Hydroxycoumarins; Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism

Topics: Acenocoumarol; Anticoagulants; Coumarins; Thromboembolism