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PubMed2003

Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial.

BACKGROUND: Several studies have demonstrated that patient self-management of oral anticoagulant therapy (OAT) can improve treatment quality. However, most of these studies were not conducted within a specialized anticoagulation care system. The objective of the present study was to determine whether patient self-management of OAT improves the quality of care delivered by anticoagulation clinics. METHODS: In this randomized study by 2 Dutch anticoagulation clinics 341 patients aged between 18 and 75 years and receiving long-term OAT were divided into 4 groups: an existing routine care group of patients untrained in self-management; a routine care group of trained patients; a group managed weekly at an anticoagulation clinic where international normalized ratios were measured by trained patients; and weekly patient self-management. A 2-step randomization procedure was followed: first, a Zelen-design randomization was performed to distribute patients (without informing them) to the existing care group or to receive training in self-management; second, trained patients were randomized to the 3 other study groups. RESULTS: Only 25.6% of invited patients agreed to participate in the training program. Patients who remained in the existing care group were within the international normalized ratio target range 63.5% of the time. The type of coumarin taken was a major predicting factor of OAT quality. In all study groups phenprocoumon outperformed acenocoumarol by 11.6% (95% confidence interval [CI], 6.6%-16.5%). Weekly management with phenprocoumon led to a 6.5% improvement (95% CI, 0.0%-13.1%) in time in the international normalized ratio target range when patients were managed at an anticoagulation clinic and to an 8.7% improvement (95% CI, 1.6%-15.9%) when patients were self-managed. Weekly management with acenocoumarol did not improve the quality of OAT. CONCLUSION: With selected patients, the quality of OAT obtained through patient self-management is at least as high as that delivered by specialized physicians at anticoagulation clinics. Weekly management of OAT with long-acting phenprocoumon has to be preferred at anticoagulation clinics or, where possible, through patient self-management.

Adult↗
PubMed2003

Genetic and environmental risk factors for oral anticoagulant overdose.

BACKGROUND: Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate. OBJECTIVES: To determine the relative frequencies of different risk factors for OA overdose including diet, concomitant diseases, drug interactions, recent increment of OA dose and CYP2C9 genetic polymorphism among hospitalised patients. MATERIALS AND METHODS: Frequencies of the different risk factors for OA overdose were determined in a prospective case-control study. Seventy-five consecutive patients with an International normalised ratio (INR) greater than 4 were matched with seventy-five control patients with an INR greater than 2 but less than 3.5 with respect to age, prescribed OA and daily dose. Genotyping of CYP2C9*2 and CYP2C9*3 allelic variants was detected by the TaqMan allelic discrimination assay. RESULTS: Drug interactions and a recent increment of OA dose were the only significant independent risk factors identified in the first analysis with odds ratio 2.13 (95% CI: 1.06-4.28) and 3.38 (95%CI: 1.51-7.57), respectively. A recent increment of OA dose was the only significant independent risk factor identified among the patients treated with coumarin derivatives (acenocoumarol or warfarin), excluding those treated with fluindione; the odds ratio was 4.3 (95% CI: 1.5-12.3). CYP2C9 genetic polymorphism did not significantly predict the increased risk of OA overanticoagulation in this study. However three homozygous CYP2C9*3/CYP2C9*3 genotype patients were found among the cases, whereas no such patients could be identified among controls. CONCLUSION: This is the first observational study investigating the role of CYP2C9 genetic polymorphism together with other environmental OA overdose risk factors. Our results support the view that although the CYP2C9*3/CYP2C9*3 genotype is associated soon after the introduction of OA with dramatic overanticoagulation, OA overdose is mostly related to environmental factors.

Administration, Oral↗
PubMed2005

Oral anticoagulation therapy in children.

Treatment of thromboembolic complications in children has been the subject of considerable research in the last decade. Recommendations for oral anticoagulant therapy in children have been extrapolated from adult clinical trials. Coumarin derivatives are the preeminent oral antithrombotic agents used in children. Warfarin, acenocoumarol and phenprocoumon are the vitamin K antagonists used in children with thrombotic complications in different countries according to their experience and familiarity within a country or region. Prospective studies from Canada and Argentina propose guidelines for administering and monitoring warfarin and acenocoumarol therapy in children. These studies highlight the difficulty of their use in pediatric patients. Infants younger than 12 months of age require increased doses to achieve and maintain the therapeutic target INR, adjustments of loading dose to achieve the target INR faster with no overshooting, more frequent INR testing and dose adjustments, and fewer INR in the target range. The current indications for oral anticoagulants in children with thrombotic complications, the side effects of these agents and the reversal of the anticoagulant effect are discussed.

Administration, Oral↗
PubMed1981

The effect of Ticlopidine upon platelet function, haemorrhage and post-operative thrombosis in patients undergoing suprapubic prostatectomy.

In order to study in its protective effect against post-operative thrombosis, Ticlopidine was administered to one out of two randomized groups of patients undergoing suprapubic prostatectomy. Bleeding time, platelet function, and haematological parameters were followed. Blood loss during operation and post-operatively were estimated, transfusions required and subjective tolerance were recorded. Among twenty-six evaluated patients receiving Ticlopidine, positive leg scans were found in four, whereas among twenty patients treated with acenocoumarol post-operatively, positive leg scans were found in seven patients. The difference is not statistically significant, thus Ticlopidine appears to offer a protection against deep venous thrombosis comparable to that of acenocoumarol. A score is introduced for comparison of the results of aggregation tests. Platelet aggregability diminished during the use of the drug, but the adhesiveness was not influenced by Ticlopidine. The bleeding time was prolonged in both groups studied. Ticlopidine did not raise per-operative blood loss and caused only slightly more haematuria post-operatively. The subjective tolerance was good.

Bleeding Time↗
PubMed2006

Contribution of CYP2C9 to variability in vitamin K antagonist metabolism.

CYP2C9 is the third most important cytochrome P450 (CYP) in terms of number of drugs metabolised. A considerable amount of information on this isoform is now available with respect to its structural biology, the mechanisms by which it can be induced and the existence of a range of variant alleles, which are often functionally significant. CYP2C9 makes a very important contribution to metabolism of vitamin K antagonist anticoagulants, and is the main oxidising enzyme for S-warfarin and S-acenocoumarol as well as contributing to phenprocoumon metabolism. A large number of studies have now shown that CYP2C9 genotype predicts dose requirement for both warfarin and acenocoumarol, with a possible contribution for phenprocoumon. Patients with variant alleles are likely to require a lower dose and may be at risk of overcoagulation and resultant bleeding, especially during the induction phase of therapy. Although CYP2C9 genotype is clearly a predictor of vitamin K antagonist dose requirement, especially in Caucasian populations in whom variant alleles are common, a number of recent studies have shown that age, genotype for the gene encoding the target gene vitamin K epoxide reductase and concomitant drugs are equally important factors in determining dose. There is a need for prospective studies to assess the value of predicting dose requirement on the basis of all these factors, including the CYP2C9 genotype.

Alleles↗
PubMed1997

Nadroparin calcium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders.

Nadroparin (nadroparin calcium) is a low molecular weight heparin with a mean molecular weight of 4.5 kD. Compared with unfractionated heparin (UFH), nadroparin has a greater ratio of anti-factor Xa to anti-factor Ha activity, greater bioavailability and a longer duration of action, allowing it to be administered by subcutaneous injection for prophylaxis or treatment of thromboembolic disorders. In clinical trials conducted in older patients (mean age usually > 60 years), nadroparin was at least as effective as UFH in preventing deep vein thrombosis (DVT) and pulmonary embolism after major general or orthopaedic surgery, and in bedridden medical patients. Nadroparin was also at least as effective as dalteparin or oral acenocoumarol in preventing thromboembolic events following general and orthopaedic surgery, respectively. When used for treatment of established DVT, nadroparin was at least as effective as intravenous UFH. Subcutaneous nadroparin, at dosages similar to those used for the treatment of DVT, produced promising results in older patients with pulmonary embolism, acute ischaemic stroke or unstable angina. In 1 study, 75% of nadroparin-treated patients were able to complete their treatment at home and 36% did not require admission to hospital; the potential pharmacoeconomic implications of these results deserve further evaluation. Overall treatment costs (drug acquisition and monitoring costs) were similar for nadroparin and UFH in a French study, but nadroparin was associated with significantly less nursing time spent on treatment delivery. Nadroparin is well tolerated by older patients. The most frequently reported adverse events in a large (n approximately 4500) placebo-controlled study in general surgical patients were wound and injection site haematoma (11.8 and 10.2%, respectively, vs approximately 6.5% for placebo). When used as prophylaxis, no significant differences in bleeding complications were noted between nadroparin and UFH or acenocoumarol recipients. Prophylactic nadroparin was associated with significantly fewer withdrawals because of adverse events than UFH in elderly bedridden medical patients. When used as treatment for DVT, nadroparin was generally associated with lower occurrences of major bleeding than intravenous UFH (0.5 to 2.3% vs 2 to 5%); however, trials were not large enough to demonstrate any significant differences between the 2 agents. Similarly, the incidence of thrombocytopenia was slightly, but generally not significantly, lower in nadroparin (< 1%) than in UFH (< or = 3.5%) recipients. Thus, nadroparin should be considered an effective and well tolerated alternative to UFH for prophylaxis and treatment of DVT in older patients, with the advantage of more convenient administration and decreased monitoring requirements.

Absorption↗
PubMed2006

Compliance-guided therapy : a new insight into the potential role of clinical pharmacologists.

BACKGROUND AND OBJECTIVE: In the field of drug noncompliance, we investigated an original approach that could give the prescribing physician, in collaboration with a clinical pharmacologist, an active role. The aim here is for the prescribing physician to take compliance into account so as to provide an optimised prescription (choice of molecule prescribed and its rhythm of administration) adapted to each patient. The example considered is that of oral anticoagulant treatment prescribed long-term. METHODS: In order to investigate the choice of the best molecule and treatment regimen for a given noncompliance pattern, we performed an in silico study with two oral anticoagulant agents, warfarin and acenocoumarol, each taken in one or two daily doses. Three linked models were used: the first model generated specific noncompliance patterns, the second model described the pharmacokinetics of oral anticoagulant agents and the third model summarised the pharmacokinetic-pharmacodynamic relations. RESULTS: Considering different patterns of noncompliance (including timing errors in drug intake and the phenomenon of drug holidays) and comparing warfarin with acenocoumarol, we identified different situations in which one agent (prescribed once or twice daily) could clearly minimise both the thromboembolic and haemorrhagic risks. However, for some specific noncompliance patterns, the choice of the optimal therapy should also be guided by the basal individual thromboembolic and haemorrhagic risks. CONCLUSION: Individualisation of drug therapy involves both drug dose and drug choice. In addition to the classical approach (i.e. drug level measurements, enzyme assays and even genetic sequence data), our study suggests that compliance-guided therapy may represent a potential, evolving way for the individualisation of prescriptions.

Humans↗
PubMed1987

Hepatic uptake and storage of warfarin. The relation with the target enzyme vitamin K 2,3-epoxide reductase.

The mechanisms of the reported dose-dependent warfarin pharmacokinetics were investigated using [14C]warfarin. When administered in microdoses (9 micrograms i.v.) to rats (male Wistars, 270-300 g), a steep distribution phase (T1/2 = 0.25 hr) was followed by a relatively slow beta-phase (T1/2 = 40 hr). The observed volume of distribution was 390 ml. This pharmacokinetic behavior contrasted highly with the one seen for higher (greater than 0.2 mg/kg) doses (unlabeled) warfarin; volume of distribution = 45 ml, T1/2 = 12.5 hr. If a "macrodose" (0.2 mg/kg) preceded (16 hr) the "microdose," "normal" pharmacokinetics were observed for the latter, suggesting a saturable "deep compartment." The administration of 4-hydroxycoumarins (i.e., acenocoumarol, phenprocoumon and warfarin) after the microdose of [14C]warfarin was in its beta-phase caused a rapid rise of plasma [14C]warfarin indicating [14C]warfarin to be displaced from the "deep compartment." The rate of appearance of [14C]warfarin was 0.3 hr-1 irrespective the 4-hydroxycoumarin used. The hepatic distribution of [14C]warfarin was investigated and the effect of a displacer thereupon. Fifty-three hours after the [14C]warfarin administration, the liver contained about 40% of the dose; 45% of it was bound to microsomes. The administration of acenocoumarol (0.2 mg/kg) at 48 hr, halved the liver content. [14C]warfarin was redistributed from microsomes (-65%) and from the 10,000 X g pellet (-65%) into the cytosol (+260%) and the plasma (+320%). Microsomal bound [14C]warfarin in vitro could not be washed out or be displaced unless dithiothreitol (50 mM) was included in the washing buffers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

[Treatment of diffuse membranous glomerulonephritis with a combination of anticoagulants and corticosteroids].

The results are reported from the administration of an original therapeutic combination, including anticoagulants (heparin and acenocoumarol) and corticosteroids to 18 patients with diffuse membranous glomerulonephritis. The anticoagulant treatment begins with heparin intravenously (30 000 U daily) and continues, after 1-2 months with acenocoumarol. The corticosteroids were applied with an initial dose of 60 mg prednison, with further gradual decrease. The treatment lasts from 7 to 60 months (18,8 months on the average). Complete clinical-laboratory remission was obtained in 14 patients (77,8%), and partial in 3 (16,7%). The remission develops 6 to 24 months (8,7 months on the average) after the initiation of the treatment. According to the author, the good therapeutic results are due to the original combination of anticoagulants with corticosteroids, not administered so far by other authors to membranous glomerulonephritis, to the rather long-term treatment and to the qualitative follow-up care.

Adrenal Cortex Hormones↗
PubMed1983

[Postoperative changes in hemostasis by heparin/dihydroergotamine prevention].

Coagulation studies and the J-125-fibrinogen-uptake-test for diagnosis of deep vein thrombosis were carried out in 244 and 288 patients resp. undergoing vaginal or abdominal hysterectomy. They were given a prophylaxis with 2 X 5000 IU calcium heparin (Calciparin) or 2 X 5000 IU sodium heparin with 0.5 mg dihydroergotamine (Heparin-Dihydergot). Control patients received acenocoumarol (Sintrom). The incidence of deep vein thrombosis was lowest in the heparin/dihydroergotamine group and was 5.9%. With calcium heparin prophylaxis it was 15.5%, and with acenocoumarol 12.2%. Plasma heparin levels and parameters of coagulation, fibrinolysis and platelet function showed that after 8 days of heparin prophylaxis with or without dihydroergotamine there is no change in hemostasis towards an increasing hypo- or hypercoagulability. Coagulation changes and the incidence of postoperative wound hematoma were identical using heparin alone or in combination with dihydroergotamine. Thus the improved effectiveness of heparin/dihydroergotamine in prevention of deep vein thrombosis which has been shown in the fibrinogen test cannot be explained by an effect onto the coagulation parameters studied. It is pointed out that a peridural anesthesia can be carried out in low-dose heparin and heparin/dihydroergotamine prophylaxis without the risk of bleeding and that the incidence of wound hematoma can be reduced by correct choice of the site of injection.

Blood Coagulation Tests↗
PubMed1997

Recombinant tissue type plasminogen activator treatment of thrombosed mitral valve prosthesis during pregnancy.

PURPOSE: Prosthetic heart valve thrombosis occurring during pregnancy is a life-threatening complication. Surgical treatment requires clot removal under cardiopulmonary bypass (CPB) and carries a high mortality. We describe the successful use of thrombolytic therapy for recurrent thrombosed valve prosthesis in a pregnant patient. CLINICAL FEATURES: A 32-yr-old patient whose pregnancy was complicated by two episodes of a thrombosed St Jude mitral prosthesis is reported. The first episode occurred at 20 wk of pregnancy during the change of oral anticoagulant therapy (acenocoumarol 4 mg a day) to sc heparin. As the patient was in cardiogenic shock, the valve thrombus was treated by clot removal under CPB., with a cross clamp time of 32 min, a perfusion pressure above 70 mmHG. There was no fetal cardiac rhythm during CPB which lasted < 45 min. The second episode occurred at the 28th gestational week in a patient in cardiogenic shock and because reoperation was thought to carry too high a risk, the thrombus was successfully treated with 50 mg recombinant tissue plasminogen activators (rtPA) i.v. Following this, the course of pregnancy was uneventful and carried to term and the patient delivered vaginally. Pain relief was achieved with intravenous patient-controlled analgesia with alfentanil (bolus 100 mug; lock out = five minutes). Although rtPA has been used before, this is the first report in which pregnancy was carried to term and standard vaginal delivery performed. CONCLUSION: This case provides evidence for the efficacy and relative safety of rtPA as thrombolytic therapy in the treatment of haemodynamically compromised valve heart thrombosis in pregnancy.

Acenocoumarol↗
PubMed2007

Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM).

BACKGROUND/OBJECTIVES: Expert oral anticoagulation management is the key to good outcomes and is performed variably in different health care systems throughout the world. We set out to assess the quality of anticoagulation management in five countries in patients receiving vitamin K antagonists (VKAs) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF), and to compare the anticoagulation management practices in these countries. METHODS AND RESULTS: This was a retrospective, multi-centre cohort study in the United States, Canada, France, Italy, and Spain. About 1,511 patients were randomly recruited from representative practices (routine medical care (RMC) in the US, Canada, and France; anticoagulation clinics in Italy and Spain) and data pertaining to their oral anticoagulation care were abstracted from their medical records. The predominant anticoagulant in use was warfarin in the US, Canada, and Italy; acenocoumarol in Spain; and fluindione in France. Documentation of care was poor in the US, Canada, and France, countries where RMC was studied. Percent INRs or time-in-therapeutic range was greater in the two anticoagulation clinic samples compared with the RMC samples. CONCLUSION: Oral anticoagulation care varies considerably from country to country. Findings suggest that anticoagulation clinic care (ACC) may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate. Condensed Abstract Oral anticoagulation management (routine medical care or anticoagulation clinic care) was retrospectively assessed in 5 countries using a uniform, structured assessment tool. Major management differences were detected, especially between anticoagulation clinic care and routine care. Documentation was often a problem in the latter setting. Less time in therapeutic INR range was noted in routine medical care. Findings suggest that anticoagulation clinic care may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate.

Acenocoumarol↗
PubMed1989

Microsomal warfarin binding and vitamin K 2,3-epoxide reductase.

Rat liver microsomal 4-hydroxycoumarin binding was studied by assaying specific [14C]warfarin binding. Microsomes of warfarin-sensitive rats contained about 40 pmole of specific binding sites per mg of microsomal protein. There was no difference for R- or S-[14C]warfarin. Neither was there any difference between the enantiomers of acenocoumarol and phenprocoumon to prevent the in vitro racemic [14C]warfarin binding. Pretreatment of the microsomes with dithiothreitol, the in vitro reductor for microsomal vitamin K epoxide reductase activity, reduced the warfarin binding. Vitamin K epoxide nor vitamin K affected the warfarin binding. Microsomes of the Welsh warfarin resistant genotype showed weak warfarin binding properties. The Scottish resistant variant, on the other hand, did not differ from sensitive microsomes. Warfarin binding was reduced in microsomes of rats to which S-warfarin was administered. The reduction in warfarin binding was linear with the inhibition of microsomal vitamin K epoxide reductase activity and was linear with the amount of S-warfarin present in the microsomes. The results show the microsomal 4-hydroxycoumarin binding to be related to the target enzyme vitamin K epoxide reductase.

Acenocoumarol↗
PubMed1989

The in vitro ketone reduction of warfarin and analogues. Substrate stereoselectivity, product stereoselectivity and species differences.

The in vitro metabolic ketone reduction of warfarin and its 4'-analogues acenocoumarol (4'-nitrowarfarin) and 4'-chlorowarfarin has been investigated using microsomal and cytosolic fractions of several species. Both subcellular fractions showed ketone reductase activity. The cytosolic fractions, in most species, exhibited strong substrate stereoselectivity as well as product stereoselectivity, i.e. the R(+)enantiomer was preferred as a substrate to be reduced mainly to the RS alcohol. Phenobarbital and methylcholanthrene induced cytosolic ketone reductase activity in the rat 5- to 11-fold and 3- to 7.4-fold, respectively. The microsomal fractions also showed substrate and product stereoselectivity. Contrary to the cytosolic fractions a general pattern for substrate and product stereoselectivity could not be seen. Stereoselectivity seemed species dependent (e.g. sheep vs bovine and pig). Rat liver microsomes showed practically no ketone reductase activity. Induction by phenobarbital or methylcholanthrene resulted in only a slight rise, if any, in rat microsomal ketone reductase activity. Both cytosolic and microsomal ketone reductases proved to be NADPH dependent. Substitution of the 4'-hydrogen of warfarin resulted in a change in reduction rates and in some cases, even in a change in substrate or product stereoselectivity. The data indicate that microsomal ketone reductases are different from cytosolic ketone reductases. Prelog's rule for product stereoselectivity of metabolic ketone reduction, when applied to the ketone reduction of the warfarin analogues did not agree with all data presented here.

Acenocoumarol↗
PubMed1986

Antithrombotic therapy in children and adolescents.

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.

Acenocoumarol↗
PubMed1993

The effect of ticlopidine upon plasma fibrinogen levels in patients undergoing suprapubic prostatectomy.

The mechanisms of the antithrombotic effect of the platelet aggregation inhibiting agent Ticlopidine might include a decrease of the plasma fibrinogen level. The effect of ticlopidine on increased fibrinogen synthesis following trauma, such as surgery, is however not known. 46 patients who underwent suprapubic prostatectomy were randomized to receive either (group A) Ticlopidine (2 x 250 mg daily) from the second preoperative day until the seventh postoperative day or (group B) placebo up till the day of surgery and further acenocoumarol against post-operatively and observed that the level and in particular the rise of the plasma fibrinogen concentration was not different in the two groups. It is concluded that compared with the standard treatment in group B ticlopidine does not influence trauma-induced fibrinogen increase.

Acenocoumarol↗
PubMed1994

Heparin-induced thrombocytopenia and thrombosis following open heart surgery.

We recently observed five cases of early thrombus formation in patients undergoing anticoagulation with subcutaneous heparin following open heart surgery. The reasons prompting surgery were as follows: one mitral valve replacement, one double valve replacement, one mitral valve reconstruction, one aortic valve replacement associated with coronary bypass. In all cases, intravenous heparin was begun on the day of surgery and replaced by subcutaneous (SC) heparin on postoperative day 1. Acute thrombocytopenia was observed between the 6th and 11th postoperative day. This was interpreted as denoting an idiosyncratic reaction to heparin which was replaced by low molecular weight heparin (LMWH) in two cases and by acenocoumarol in the other cases. Massive thrombosis of the aortic valve resulted in the death of one patient. Thrombosis of the left atrium occurred in three patients (two of whom had a transient ischemic attack (TIA)). One patient had aorto-iliac thrombosis. Successful reoperation was carried out in four of the five patients. Although heparin-induced thrombocytopenia and thrombosis [HITT] is a rare complication of heparin therapy, serial platelet count monitoring and in vitro platelet aggregation tests are mandatory in the diagnosis of this syndrome. Discontinuation of heparin is indicated as soon as the syndrome is recognized and the institution of aspirin is recommended if the thromboembolic complication requires reoperation and reexposure to heparin.

Acenocoumarol↗
PubMed2004

[Splenic rupture and anticoagulant therapy].

Splenic rupture associated with anticoagulant therapy is a rare entity. We report a case of spontaneous splenic rupture in a 62-year-old man who was treated by acenocoumarol orally after an aortic-valve replacement. Unrecognised, minor trauma may lead to splenic haemorrhage in patients receiving anticoagulant therapy. The symptoms and signs may mimic those of acute myocardial infarction and cardiogenic shock. Early diagnosis is essential. Reversal of the anticoagulant and emergent splenectomy are the treatments of choice.

Acenocoumarol↗