Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease

Abstract

To cite this version:Reinhild Klein. Evidence for immunological (allergic) mechanisms in a subgroup of patients with phenprocoumon-induced liver disease. Abstract Purpose 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. Patients and 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.

Antibodies to soluble liver antigen in patients with various liver diseases: A multicentre study

“… described three DILI patients with anti‐SLA seropositivity. This association was not seen in our or another study . Various drugs, including nitrofurantoin, diclofenac, minocycline and atorvastatin, are considered to be potential triggers of AIH or some of AIH are indolent and become clinically evident after DILI .…”

Bleeding Complications and Liver Injuries During Phenprocoumon Treatment

“…The predominance of women among patients with phenprocoumon-associated liver disorders in our study agrees well with other researchers' results-although contrasting findings have been reported (32). A non-dose-related immunologic mechanism was recently shown to lie behind phenprocoumon-associated liver damage (33), and both hepatocellular and cholestatic liver injuries have been described (34,35). There is no consensus, however, regarding the assignment of cases to the different damage types (e4).…”

Differential effects of the tumor necrosis factor alpha-blocker infliximab and etanercept on immunocompetent cells in vitro

“…This range has been proven in earlier studies to give reliable and reproducible results without significant changes, and cells are still viable after 24 h [24,[26][27][28][29][30]. PBMC were collected from the interface, washed twice in Hanks' salt solution and adjusted to 1 Mio cells/ml in RPMI 1640 medium supplemented with gentamycin and 25% autologous serum as reported in previous studies [24,26,[29][30][31].…”