Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease.
OBJECTIVE
Phenprocoumon-induced liver injury is a rare complication of oral anticoagulation. The mechanisms leading to this side effect are not entirely clear. Here we present data that at least in a subgroup of patients in whom phenprocoumon-induced liver disease was suspected, immunological processes may play an important role.


METHODS
Thirty patients with suspected phenprocoumon-induced liver disease from different hospitals in Germany were analyzed. Peripheral blood mononuclear cells (PBMC) of these patients were tested in the lymphocyte transformation test (LTT) for reactivity with phenprocoumon in vitro. As controls, PBMC were isolated from ten individuals treated with phenprocoumon but without any side effects, and from ten healthy individuals who have never received the drug.


RESULTS
Fifteen of the 30 patients had sensitized lymphocytes toward phenprocoumon as shown by LTT. Four patients had taken the drug for more than 5 years; in one patient, liver disease appeared after 1 day of phenprocoumon intake. There was no correlation between a positive LTT and clinical/laboratory parameters. None of the 20 controls had sensitized lymphocytes toward phenprocoumon.


CONCLUSIONS
Applying the LTT, we were able to unravel the cause of suspected phenprocoumon-induced liver injury as a drug allergic reaction in 15 out of 30 analyzed patients.
Klein
Reinhild
R
Department of Internal Medicine II, University of Tuebingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany. reinhild.klein@med.uni-tuebingen.de
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D005858:Germany; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000009:adverse effects* / Q000276:immunology
D000925:Anticoagulants; D010644:Phenprocoumon