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PubMed1988

Vitamin K 2,3-epoxide reductase: the basis for stereoselectivity of 4-hydroxycoumarin anticoagulant activity.

1. The administration of S-warfarin (1 mg kg-1 i.v.) to rats that were pre-loaded 48 h before with tracer doses (6 micrograms) of 14C-labelled R- or S-warfarin caused the plasma levels of these compounds to increase. This is due to the substitution of the microsomal (vitamin K 2,3-epoxide (K0) reductase) bound R- or S-[14C]-warfarin by the unlabelled 4-hydroxycoumarin administered. The rate of reappearance was 3-4 fold higher for R- than for S-warfarin; t1/2 of release: 1.2 +/- 0.04 and 3.7 +/- 0.6 h, respectively. 2. Liver microsomes prepared from rats pretreated with R- or S-[14C]-warfarin, released these compounds only in the presence of dithiothreitol (DTT; 10 mM). The rate of release was higher for R- than for S-warfarin-treated microsomes. 3. Liver microsomes treated in vitro with R- or S-acenocoumarol could be reactivated by DTT (10 mM). Reactivation was higher for the R- than for the S-acenocoumarol-treated microsomes. 4. The microsomal vitamin K0 reductase activity under 'normal' assay conditions ([DTT] = 2 mM) was as sensitive for R- as for S-4-hydroxycoumarins. At elevated DTT concentrations (= 42 mM) the rate of vitamin K0 conversion was about 1.5 fold higher in the presence of the R-isomers than in the presence of the S-isomers. For instance, at 2 mM DDT the reductase activities in the presence of 2.6 microM R- and S-warfarin were about 15% of control. At 42 mM DTT the activities were 90 and 65% of control, respectively. 5. In the in vitro experiments acenocoumarol appeared to be more potent than warfarin and phenprocoumon. 6. The following mechanism is proposed: vitamin K0 reductase becomes oxidized during substrate reduction. The oxidized (i.e. inactive) form binds equally to the R- and S-enantiomers of 4- hydroxycoumarins. The attached (covalently bound?) coumarin is released by the reactivation (i.e. reduction) of the enzyme. However, the rate of reactivation is strongly attenuated by the attached coumarin. This effect is more pronounced for the S-configuration of the 4-hydroxycoumarin anticoagulants.

4-Hydroxycoumarins↗
PubMed2001

Reviparin: a review of its efficacy in the prevention and treatment of venous thromboembolism.

UNLABELLED: Reviparin (reviparin sodium) is a low molecular weight heparin (LMWH) that catalyses the inactivation of factors Xa and IIa by binding to antithrombin, which ultimately leads to the inhibition of the clotting cascade. It is administered subcutaneously. Reviparin 7,000 to 12,600 anti-XaIU/day was found to be as effective as intravenous unfractionated heparin in preventing the clinical recurrence of acute deep vein thrombosis (DVT) and/or pulmonary embolism in 1 large randomised, multicentre trial (COLUMBUS) and was significantly more effective than intravenous unfractionated heparin in the prevention of recurrent venous thromboembolism in another large randomised, multicentre trial (CORTES). Reviparin has also been compared with unfractionated heparin in children with established DVT. However, the trial was under-powered and no conclusion could be made regarding comparative efficacy. As prophylaxis, reviparin 1,750 anti-XaIU once daily was as effective as unfractionated heparin 5,000IU twice daily in 1,311 patients undergoing abdominal surgery and, in a once daily dosage of 4,200 anti-XaIU, was as effective as subcutaneous enoxaparin sodium 40 mg/day or acenocoumarol in patients undergoing hip replacement surgery. Reviparin 1,750 anti-XaIU also effectively prevented DVT. compared with no treatment, in patients undergoing knee arthroscopy. It was also more effective than placebo in patients with brace immobilisation of the lower extremity. Reviparin was compared with 'standard care' in children with central venous lines. However, the trial was too small to make conclusions regarding its efficacy. Comparative data indicate that reviparin is at least as well tolerated as heparin and enoxaparin sodium. However, in a large (n = 1,279) trial there were significantly fewer major bleeding episodes in patients receiving reviparin than in patients given the oral anticoagulant acenocoumarol. The most commonly reported adverse events in therapeutic trials have been intraoperative blood loss and postoperative bleeding complications such as wound haematoma, bruising and injection site haemorrhage. Reviparin was also well tolerated in 2 studies in children aged < or = 16 years. CONCLUSION: Reviparin has shown efficacy in the treatment of established DVT and in the prevention of postoperative DVT after moderate and high risk surgery and was as effective as enoxaparin sodium or acenocoumarol in patients undergoing hip replacement surgery. As an effective and well tolerated antithrombotic agent, reviparin is likely to assume a significant role in the treatment and prevention of DVT, as it appears to have a preferable tolerability profile to subcutaneous heparin after moderate risk surgery and is at least as effective as intravenous heparin in the treatment of established DVT.

Adult↗
PubMed2004

[Long-Term Therapy With Indirect Anticoagulants in Patients With Nonvalvular Atrial Fibrillation (Prospective Follow-Up Study). Part II. Effectiveness and Safety].

AIM: To assess efficacy and safety of long-term international normalized ratio (INR) guided therapy with acenocoumarol in patients with nonvalvular atrial fibrillation. MATERIAL: Patients (n=100) with nonvalvular atrial fibrillation and at least 1 risk factor of thromboembolic complications. METHODS: Ischemic strokes, episodes of systemic thromboembolism and hemorrhagic complications were registered during 3 years of treatment with acenocoumarol (target INR 2.0-3.0). RESULTS: Annual rates of ischemic strokes, hemorrhagic complications and major bleeding were 0.7, 14.4 and 1.1%, respectively. No episodes of thromboembolism were registered in patients with history of thromboembolic complications. Basing on data collected predictors of bleeding complications in patients with atrial fibrillation during long term treatment with acenocoumarol were elucidated.

Anticoagulants↗
PubMed1977

[Effect of alclofenac on the prothrombin level in patients under treatment with anticoagulants].

Simultaneous administration of the anticoagulants acenocoumarol, phenprocoumon or chlorindion and the antirheumatic substance alclofenac in long term trials has no observable influence on the prothrombin time of stabilized patients. When the anticoagulant (acenocoumarol or phenprocoumon) and the alclofenac therapy are begun simultaneously, a variation of the dose is necessary. Either a one-third lower initial dosage can be given, or, after attaining the maximal anticoagulation effect on the prothrombin time (48 h after beginning acenocoumarol therapy, 72 h with phenprocoumarol), a lower daily dosage must be administered once, in comparison to the other group without alclofenac therapy. The maintenace dosage is not influenced by alclofenac.

Aged↗
PubMedDate not supplied

Liquid chromatographic determination of coumarin anticoagulants in tablets.

A simple and rapid liquid chromatographic method is described for the qualitative and quantitative determination of 5 coumarin anticoagulants in tablet composites and individual tablets. Analyses are carried out on a C18 reverse phase column using tetrahydrofuran-methanol-water-acetic acid (35 + 10 + 65 + 0.1) as mobile phase and photometric detection at 311 nm. The coefficients of variation for 10 consecutive injections of a mixed standards solution ranged from 0.28% for ethyl biscoumacetate to 0.78% for acenocoumarol. Standard recoveries were as follows: acenocoumarol, 99.3%; dicumarol, 99.6%; phenprocoumon, 101.6%; and warfarin sodium, 99.0%. The method was linear between 2 and 8 micrograms of drug injected. Assay results agreed favorably with those of the USP XX methods for dicumarol, phenprocoumon, and warfarin, and the NF XIV method for acenocoumarol. In addition, close correspondence was found with the results previously reported for the same drugs by a semiautomated spectrophotometric method. The content uniformity testing of individual 50 mg dicumarol tablets and 5 mg warfarin sodium tablets by the proposed method gave average (SD) values of 100.32% (0.64) and 101.00% (0.14), respectively, whereas these values were 101.60% (1.81) and 101.80% (0.18), respectively, by the method of USP XX.

Anticoagulants↗
PubMed2002

Extended venous thromboembolism prophylaxis after total hip replacement: a comparison of low-molecular-weight heparin with oral anticoagulant.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Acenocoumarol↗
PubMed2003

[Identification of factors responsible for oral over-anticoagulation in outpatients with heart disease].

BACKGROUND: Few studies have attempted to investigate the clinical course or identify factors responsible for excessive anticoagulation in patients with heart disease. OBJECTIVES: To determine the incidence of excessive anticoagulation in outpatients with heart disease treated with acenocoumarol, analyze the factors related with over-anticoagulation, and identify bleeding complications. PATIENTS AND METHOD: This 7-month prospective observational study included consecutive outpatients anticoagulated with acenocoumarol. They were seen in an anticoagulation unit. The high INR group of 55 over-anticoagulated patients had at least one test with INR > 5. The control group of 49 patients had INR results strictly within therapeutic range. RESULTS: A total of 3,683 INR determinations were made in 512 patients. Seventy-seven tests had an INR > 5 (a 2% overall incidence of high-INR). In the group of 55 INR < 5 patients, 31% had more than one INR determination > 5 during follow-up. Multivariate analysis identified four variables as independent predictors of over-anticoagulation: artificial heart valve, poor treatment compliance, addition of potentially interactive new drugs, and illness in the last month. The high-INR group patients had more bleeding episodes (21.8 vs 4.08%; p = 0.008), one of which was major. CONCLUSION: The incidence of excessive oral anticoagulation in our outpatient population was similar to that reported in other studies. Patients with INR > 5 had more total bleeding complications, mostly minor. It is recommended to proceed carefully with oral anticoagulant therapy in patients with an artificial heart valve, suspected poor treatment compliance, addition of potentially interactive new drugs, and illness in the last month.

Acenocoumarol↗
PubMed1989

The interaction of the prostaglandin E derivative rioprostil with oral anticoagulant agents.

The prostaglandin E1 analogue rioprostil was tested for potential interaction with oral anticoagulant therapy in healthy male volunteers. The effect of rioprostil (0.3 mg, twice a day) was investigated on acenocoumarol (10 mg per subject, n = 7) and phenoprocoumon (0.2 mg/kg, n = 6) single-dose pharmacokinetics and pharmacodynamics. Plasma levels of thrombotest, prothrombin (factor II), and factor VII activities were assayed. Rioprostil, 7 days pretreatment, did not affect control parameters of blood coagulation activity. During the rioprostil period the effect of phenprocoumon on thrombotest and factor VII activities was significantly weaker (p less than 0.02, ANOVA) compared with the control experiment. The effect of acenocoumarol on thrombotest activity was significantly weaker at 24 and 31 hours. None of the pharmacokinetic parameters tested were affected by rioprostil medication. The findings suggest that prostaglandins, at least those of the E series, attenuate the anticoagulant action of the oral anticoagulant agents by a mechanism not related to any pharmacokinetic interaction.

4-Hydroxycoumarins↗
PubMed1991

[An idiopathic floating left-ventricular thrombus].

Four weeks after appendicectomy a 28-year-old man developed dragging pains in the left calf. Left popliteal, posterior tibial and dorsalis pedis arteries could not be palpated. Angiography revealed an embolic occlusion of the left superior femoral artery at the level of the adductor canal. Echocardiography demonstrated a pedunculated left ventricular thrombus, 3.5 x 2.0 cm, as a possible source of the embolus. After successful trifurcation embolectomy and saphenous vein patch-plasty acenocoumarol, 4 mg/d and heparin, 3 x 7500 IU/d were administered. Because the thrombus failed to shrink, systemic thrombolysis, initially 750,000 IU streptokinase and 3000 IU heparin i.v., was begun. After five days the thrombus diameter had decreased to 0.7 cm. But because thrombus movement had increased, streptokinase was replaced by 70 IU/d ancrod i.v. The thrombus completely disappeared within two weeks. The patient was symptom-free during the period of anticoagulation with acenocoumarol. Six months later echocardiography confirmed the absence of thrombus in the left ventricle.

Acenocoumarol↗
PubMed2001

Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis.

PURPOSE: The purpose of this study was to evaluate whether low molecular weight heparin (LMWH) could be equal or more effective than conventional oral anticoagulants (OAs) in the long-term treatment of deep venous thrombosis (DVT). METHODS: One hundred fifty-eight patients with symptomatic DVT of the lower limbs confirmed by means of duplex ultrasound scan were randomized to receive 3 to 6 months' treatment with nadroparine calcium or acenocoumarol. Quantitative and qualitative duplex scan scoring systems were used to study the evolution of thrombosis in both groups at 1, 3, 6, and 12 months. RESULTS: During the 12-month surveillance period, two (2.5%) of the 81 patients who received LMWH and seven (9%) of the 77 patients who received OAs had recurrence of venous thrombosis (not significant). In the LMWH group no cases of major bleeding were found, and four cases (5.2%) occurred in the OA group (not significant). The mortality rate was nine (11.1%) in the LMWH group and 7.8% in the OA group (not significant). The quantitative mean duplex scan score decreased in both groups during the follow-up and had statistical significance after long-term LMWH treatment on iliofemoral DVT (1, 3, 6, and 12 months), femoropopliteal DVT (1-3 months), and infrapopliteal DVT (first month). Duplex scan evaluation showed that the rate of venous recanalization significantly increased in the common femoral vein at 6 and at 12 months and during each point of follow-up in the superficial and popliteal veins in the LMWH group. Reflux was significantly less frequent in communicating veins after LMWH treatment (17.9% vs 32.2% in the OA group). The reflux rates in the superficial (22.4% in the LMWH group, 30.6% in OA group) and deep (13.4% vs 17.7%) venous system showed no significant differences between groups. CONCLUSIONS: The unmonitored subcutaneous administration of nadroparine in fixed daily doses was more effective than oral acenocoumarol with laboratory control adjustment in achieving recanalization of leg thrombi. With nadroparine, there was less late valvular communicating vein insufficiency, and it was at least as efficacious and safe as oral anticoagulants after long-term administration. These results suggest that LMWHs may therefore represent a real therapeutic advance in the long-term management of DVT.

Acenocoumarol↗
PubMed1990

Reduced axial bone mineral content in patients taking an oral anticoagulant.

Recent literature indicates that the vitamin K cycle plays a role in the calcification process, presumably via its intervention on gamma-carboxylation of the noncollagenous proteins of bone osteocalcin and matrix gamma-carboxyglutamic acid protein. The major clinical evidence of this interference is fetal bone defect caused by oral anticoagulants given to the mother during the first trimester of pregnancy. No bone abnormalities have been reported so far in adults receiving oral anticoagulants. We studied 56 women who had had cardiac valve replacement and who were given acenocoumarol as anticoagulant, and 61 age-matched women who were in the same New York Heart Association functional class but who were not taking anticoagulants. Osteocalcin serum levels were comparable between the two groups; bone density values measured at appendicular bone were significantly lower in patients taking acenocoumarol. No significant correlation was found between duration of treatment and bone density. Significant osteopenia was present in the women being treated with oral anticoagulants.

1-Carboxyglutamic Acid↗
PubMedDate not supplied

Effect of low-dose aspirin on the international normalized ratio variability in patients with mechanical heart valve prostheses.

An increased risk of bleeding is associated with a more intense oral anticoagulation, a greater international normalized ratio (INR) variability and the use of aspirin. We studied the INR variability of patients (n = 121) with modern heart valves who had been prospectively randomized to receive acenocoumarol at a targeted INR of 2.4-3.6 plus aspirin 100 mg/day or acenocoumarol alone at the same dosage, to evaluate whether aspirin influences variability and thus the risk of bleeding. Variability was similar in patients with no events regardless of the use of aspirin. A statistically significantly higher variability was observed in patients with bleeding events independently of the use of aspirin. Nevertheless, the concomitant use of aspirin in patients with a high variability should be monitored closely and thoroughly.

Acenocoumarol↗
PubMed2000

Antiplatelet is superior to anticoagulant treatment after coronary stenting: fewer coronary and other events within 30 days after stenting.

Stent prosthesis is a high efficacious method with low complication rates. However, the ideal adjunctive therapy following stent implantation remains controversial. The authors compared the effectiveness and complication rates of aspirin-ticlopidine antiplatelet therapy vs. anticoagulant therapy with acenocoumarol within 30 days following stent prosthesis. They prospectively studied 404 patients following stent prosthesis while randomly receiving anticoagulant (Group A: 201 patients) vs. antiplatelet treatment (Group B: 203 patients). Groups A and B were similar in demographic data (age, gender), stent location, clinical presentation, indication of stenting, and type of implanted stent. Chi-square test, t test, and Wilcoxon test for two samples were used for statistical analysis of the results. Stent implantation was attempted in 434 cases. This was successful in 70/85 (82%) of the bailout, 122/135 (90%) of the suboptimal, and 212/214 (99%) of the elective cases. In 201 patients anticoagulant treatment with acenocoumarol was administered for 4 weeks (group A), while 203 received antiplatelet treatment with ticlopidine (group B). The need for reintervention was less and total cardiac events were fewer in group B than in group A: three (1.5%) and nine (4.4%) vs 18 (9%) and 29 (14.4%), p<0.0008 and p<0.006 respectively. Hemorrhagic complications and total noncardiac events were fewer in group B than in group A: six (3%) and six (3%) vs. 18 (9%) and 19 (9.5%), p<0.01 and p<0.007 respectively. The length of hospital stay was shorter in group B than in A, p<0.0001. In conclusion, in this study of intracoronary stenting the authors had a high success rate in 434 attempted cases. Antiplatelet therapy was accompanied by fewer cardiac and noncardiac 1 month events when compared with anticoagulant therapy, supporting its role as the adjunctive treatment of choice post-stenting for the time being.

Acenocoumarol↗
PubMed2003

Compliance and stability of INR of two oral anticoagulants with different half-lives: a randomised trial.

The aim of the study was to assess the respective roles of the half-life of elimination of oral anticoagulants and patient education as causes of instability of anticoagulation level in patients on oral anticoagulant therapy. Patients were randomised to receive either warfarin (long half-life) or acenocoumarol (short half-life) and either intensive or standard education, according to a factorial design. Instability of oral anticoagulant therapy was evaluated by the percentage of INRs and the time within the target range, and the variability between successive measurements. Compliance was assessed by means of electronic pill bottles. Eighty-six patients were included. Apart from the variability index, instability was similar between groups. Correlations between compliance and instability were observed only in the acenocoumarol group. No difference was found between the education groups. In patients starting oral anticoagulant therapy, dose determination may be the most important factor contributing to instability.

Acenocoumarol↗
PubMed2004

[Extent and quality of anti-coagulation treatment with coumarin derivatives by the Dutch Thrombosis Services].

OBJECTIVE: To obtain an impression of the extent and quality of the anti-coagulation treatment with coumarin derivatives carried out by the Thrombosis Services in the Netherlands. DESIGN: Descriptive. METHOD: Data were drawn from the medical annual reports of 62 of the 63 Thrombosis Services in the Netherlands over the period 1998-2002. In 2002 the Thrombosis Services treated 325,072 patients and performed 4,469,730 INR laboratory tests. The half-yearly figures produced by the Thrombosis Services were calculated as an average percentage per year per thrombosis service and then recalculated as a percentage per year. RESULTS: Seventy-three per cent of the patients were treated for an arterial and 27% for a venous indication. Depending on the required intensity of anticoagulation a mean of 74-78% of the long-term treated patients fell within the therapeutic range and a mean of 6-10% below. The mean number of major bleedings per 100 treatment years was 1.0. A mean of 79% of the patients was treated with acenocoumarol and 21% with phenprocoumon. When acenocoumarol was used, a mean of 72-77% fell within the therapeutic range and in the case of phenprocoumon 79-82%. In the last few years the number of patients had increased due to a growing number of patients treated for atrial fibrillation. The percentages of INR within the therapeutic range were unchanged or showed a slight increase. CONCLUSION: The quality of the anticoagulation therapy with coumarin derivatives was good or acceptable.

Acenocoumarol↗
PubMed2004

[A retrospective survey on practice of oral anticoagulant therapy in patients with cardiovascular diseases].

INTRODUCTION: 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. AIM AND METHODS: 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. RESULTS AND CONCLUSIONS: 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.

Acenocoumarol↗
PubMed1994

Assessment of therapeutic quality control in a long-term anticoagulant trial in post-myocardial infarction patients.

Various methods have been described to evaluate efficacy of anticoagulant therapy using the international normalized ratio (INR). We compared the following approaches: (1) total INR's or the most recent measurement; (2) percent time within therapeutic range, with INR changing directly or halfway between visits; and (3) total observation time assuming INR changing linearly. The study population comprised 1700 post myocardial infarction patients. Treatment comprised 3725 patient-years. There were 61,471 INR assessments with target therapeutic level of 2.8-4.8. Acenocoumarol as well as phenprocoumon were employed. Therapeutic achievement in the first months of treatment was low: less than 60% of INR's were in range. Treatment stabilized after 6 months. Patients on acenocoumarol were within range 70% of the time compared to 80% for phenprocoumon. Method 3 is preferred because it incorporates time and is capable of calculating incidence rates at different INR levels. Our findings call for an urgent improvement of standard of anticoagulant control in the first months following commencement of treatment.

Acenocoumarol↗
PubMed1996

[Liver injury caused by coumarin anticoagulants: experience of the IKS (Intercanton Monitoring Station) and the SANZ (Swiss Center for Drug Monitoring)].

Drug-induced liver diseases are potentially avoidable. Hepatotoxic drugs can mimic virtually any form of liver disease. Among all voluntary adverse drug reaction reports to central registries, 4-7% refer to drug-induced liver diseases. We analyze all cases of coumarin-induced hepatic injuries reported on a voluntary basis to the Swiss Drug Monitoring Centre (SANZ) and the Pharmacovigilance Centre (IKS) from 1981 to 1995. During this period the SANZ collected 9720 reports, 674 of which (6.9%) referred to the liver and the biliary tract. In only 11 reports an oral anticoagulant was involved. In 8 cases we assumed at least a possible causal relationship. 2 more cases were reported directly to the IKS. Among these 10 cases 7 were related to phenprocoumon and 3 to acenocoumarol. In 4 cases elevated concentrations of liver enzymes were measured 2-7 days after the beginning of therapy. In the remaining 6 cases the clinical picture was so severe that the patients had to be hospitalized. These 10 cases are discussed and compared with the cases published in the literature. According to our data, hepatic disorders induced by coumarin-anti-coagulants are rare. If hepatitis is diagnosed in a patient treated with oral anticoagulants, the differential diagnosis of a coumarin-induced hepatic injury has to be considered. Crossreactions between the coumarin derivatives phenprocoumon and acenocoumarol are possible.

Acenocoumarol↗