Antikoagulation und Gerinnungsanalyse, Interpretation — Schnellorientierung

Heparin-induced thrombocytopenia is a relatively common antibody-mediated drug reaction. We studied the temporal relation between previous or current heparin therapy and the onset of heparin-induced thrombocytopenia. We examined the time between the start of heparin therapy and the onset of thrombocytopenia in 243 patients with serologically confirmed heparin-induced thrombocytopenia. We also investigated the persistence of circulating heparin-dependent antibodies by performing a platelet serotonin-release assay and an assay for antibodies against platelet factor 4. The outcome in seven patients who had previously had an episode of heparin-induced thrombocytopenia and were later treated again with heparin was also examined. A fall in the platelet count beginning four or more days after the start of heparin therapy occurred in 170 of the 243 patients (70 percent); in these patients, a history of previous heparin treatment did not influence the timing of the onset of thrombocytopenia. In the remaining 73 patients (30 percent), the onset of thrombocytopenia was rapid (median time of onset, 10.5 hours after the start of heparin administration); all these patients had been treated with heparin within the previous 100 days. During recovery from thrombocytopenia, heparin-dependent antibodies in the serum fell to undetectable levels at a median of 50 to 85 days, depending on the assay performed. In the seven patients who were given heparin again after the disappearance of heparin-dependent antibodies, a new episode of heparin-induced thrombocytopenia did not occur. Heparin-induced thrombocytopenia can begin rapidly in patients who have received heparin within the previous 100 days. Heparin-dependent antibodies do not invariably reappear with subsequent heparin use.

To evaluate the quality of studies about drugs and food interactions with warfarin and their clinical relevance. MEDLINE and TOXLINE databases from 1966 to October 1993 using the Medical Subject Headings warfarin, drug interactions, and English only. All articles reporting original data on drug and food interactions with warfarin. Each report, rated independently by at least two investigators (using causality assessment), received a summary score indicating the level of assurance (level 1 = highly probable, level 2 = probable, level 3 = possible, and level 4 = doubtful) that a clinically important interaction had or had not occurred. Inter-rater agreement was assessed using a weighted kappa statistic. Of 793 retrieved citations, 120 contained original reports on 186 interactions. The weighted kappa statistic was 0.67, representing substantial agreement. Of 86 different drugs and foods appraised, 43 had level 1 evidence. Of these, 26 drugs and foods did interact with warfarin. Warfarin's anticoagulant effect was potentiated by 6 antibiotics (cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, and miconazole); 5 cardiac drugs (amiodarone, clofibrate, propafenone, propranolol, and sulfinpyrazone); phenylbutazone; piroxicam; alcohol (only with concomitant liver disease); cimetidine; and omeprazole. Three patients had a hemorrhage at the time of a potentiating interaction (caused by alcohol, isoniazid, and phenylbutazone). Warfarin's anticoagulant effect was inhibited by 3 antibiotics (griseofulvin, rifampin, and nafcillin); 3 drugs active on the central nervous system (barbiturates, carbamazepine, and chlordiazepoxide); cholestyramine; sucralfate; foods high in vitamin K; and large amounts of avocado. Many drugs and foods interact with warfarin, including antibiotics, drugs affecting the central nervous system, and cardiac medications. Many of these drug interactions increase warfarin's anticoagulant effect.