acenocoumarol and Hemorrhagic-Disorders

Coumarin anticoagulants are prone to drug-drug interactions. For example, antibiotic drugs may enhance the anticoagulant effect of coumarins. However, whether such interactions are associated with an increased risk of bleeding, and if so, how frequently this occurs remains unknown.. To assess the risk of major bleeding associated with the concomitant use of antibiotic drugs and coumarin anticoagulant therapy.. We analyzed a retrospective cohort study including all users of acenocoumarol or phenprocoumon in the PHARMO Record Linkage System (age range: 40-80 years). All patients were followed up until end of last coumarin treatment, hospitalization for bleeding, death, or end of study period. For each patient, the number of days on either coumarins alone, or on coumarins in combination with antibiotic drugs was determined. From these data, the relative risks of major bleeding were calculated.. A total of 52,102 users of acenocoumarol and 7885 users of phenprocoumon met the inclusion criteria of our study cohort and contributed 139,159 person-years of follow-up. During follow-up, 838 patients (1.4%) were hospitalized for a bleeding while taking coumarins. Of the 62 different antibiotics taken by study members, 19 were associated with a bleeding episode. Of these, 10 were associated with a statistically significant increased bleeding risk. The relative risk of bleeding was three to five for doxycycline, amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, cotrimoxazole, azithromycin and pheneticillin, nine for tetracycline and 43 for cefradine and neomycin.. Based on relative risks and incidence of use, amoxicillin (alone or with clavulanic acid) and doxycycline are the main antibiotic drugs associated with major bleeding when used in combination with coumarin.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Anticoagulants; Doxycycline; Drug Synergism; Female; Follow-Up Studies; Hemorrhage; Hemorrhagic Disorders; Hospitalization; Humans; Male; Middle Aged; Netherlands; Phenprocoumon; Retrospective Studies; Risk

The effectiveness of a commercial drug containing fibrinogen, thrombin and factor XIL (Tissucol, Immuno) was assessed in 127 patients receiving oral anticoagulant treatment with acenocoumarin who were subjected to 183 minor surgical procedures: 107 exodontia, 53 periodontal procedures, 17 combinations of the former, 4 liver biopsies and 2 skin biopsies. All but the liver biopsies were performed in the outpatient clinic. Mild haemorrhage appeared in 21 instances. None of the patients required systemic administration of coagulation factors, and the maneuvers did not take any longer than in patients with integrity of the coagulation mechanisms. The outstanding benefits of this technique are: less discomfort for patients, who can be subjected to a single procedure while otherwise requiring several sessions; anticoagulation needs not be discontinued, subcutaneous heparin being otherwise necessary; low risk of complications and avoidance of substitutive therapy; lesser economic burden, as no hospital admission is needed.

Topics: Acenocoumarol; Adult; Aged; Ambulatory Surgical Procedures; Biopsy; Drug Evaluation; Female; Fibrin Tissue Adhesive; Hemorrhage; Hemorrhagic Disorders; Hemostasis, Surgical; Humans; Liver; Male; Middle Aged; Periodontics; Safety; Skin; Tooth Extraction

A 62-year-old man developed resistance to coumarin congeners during treatment with phenprocoumon (Marcoumar) and acenocoumarol (Sintrom), requiring at least triple the usual therapeutic dose and plasma concentration of phenprocoumon for satisfactory anticoagulation. After 8 months on this high dosage, the patient suddenly developed haemorrhagic diathesis. The medication was therefore discontinued. The resistance could not be ascribed to impaired absorption or enhanced metabolism.

Topics: 4-Hydroxycoumarins; Acenocoumarol; Drug Resistance; Hemorrhagic Disorders; Humans; Male; Middle Aged; Phenprocoumon

Topics: Acenocoumarol; Animals; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Blood Proteins; Cholesterol; Dietary Fats; Endotoxins; Hemorrhage; Hemorrhagic Disorders; Rats; Salmonella typhi; Shock, Septic; Shock, Surgical; Thrombosis; Triamcinolone

Coagulation studies were carried out on 10 patients who bled during anticoagulant therapy, in whom no other underlying cause for bleeding could be demonstrated, and 10 patients with similar degrees of hypoprothrombinemia who were not bleeding. The average age and sex distribution of the two groups was similar, and no association was noted between the occurrence of hemorrhage and the type of anticoagulant used, the duration of treatment or the nature of the underlying disease. Comparison of the results revealed no differences in the levels of factors II, VII, IX and X or in the glass and silicone (Siliclad) clotting time, the thromboplastin generation test and Thrombotest. It was concluded that all patients on anticoagulant drugs whose prothrombin time is in the therapeutic range or longer are potential bleeders and that one cannot necessarily predict those who will bleed on the basis of coagulation studies.

Topics: Acenocoumarol; Anticoagulants; Blood Coagulation Tests; Coumarins; Dicumarol; Drug Therapy; Geriatrics; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Indans; Phenindione; Prothrombin Time; Warfarin