Unusual liver damage ensuing after warfarin administration in a pregnant woman with caval thrombosis.

Liver injury associated with oral anticoagulant treatment is a rare event and may show as an acute cholestatic and/or mixed hepatocellular/cholestatic pattern of hepatic enzyme abnormalities [ 1 Den Boer W. Loeliger E.A. Phenprocoumon-induced jaundice. Lancet. 1980; 1: 912 PubMed Google Scholar , 2 De Man R.A. Wilson J.H.P. Schalm S.W. Ten Kate F.J.W. Van Leer E. Phenprocoumon-induced hepatitis mimicking non-A, non-B hepatitis. J Hepatol. 1990; 11: 318-321 Abstract Full Text PDF PubMed Scopus (23) Google Scholar , 3 Adler E. Benjamin S.B. Zimmerman H.J. Cholestatic liver injury related to Coumadin exposure. Arch Intern Med. 1986; 146: 1837 Crossref PubMed Scopus (21) Google Scholar , 4 Hohler T. Schnutgen M. Helmreich-Becker I. Mayet W.J. Mayer-zum-Buschenfelde K.H. Drug induced hepatitis: a rare complication of oral anticoagulants. J Hepatol. 1994; 21: 447-449 Abstract Full Text PDF PubMed Scopus (45) Google Scholar , 5 Koch S. Beurton I. Bresson-Hadni S. Monnot B. Hrusovsky S. Becker M.C. et al. Hepatite aigue cytolytique a la coumarine. Deux cas. Gastroenterol Clin Biol. 1997; 21: 223-225 PubMed Google Scholar , 6 Castedal M. Aldenborg F. Olsson R. Fulminant hepatic failure associated with dicoumarol therapy. Liver. 1998; 18: 67-69 Crossref PubMed Scopus (7) Google Scholar ]. We report on the case of a 37-year-old female seen in the Liver Unit in February 1998 because of deranged liver function tests. During the previous month, whilst pregnant at 32 weeks of gestation, she noted progressive lower limb oedema. A Doppler ultrasound revealed infra-renal caval thrombosis and delivery was induced at 34 weeks. Liver and renal function tests were normal before delivery and in the immediate post delivery phase. A thrombophilia screen revealed only protein S deficiency (Total 40, free 20, n.v. 70–140%). Soon after delivery, the patient was started on subcutaneous unfractionated heparin; then switched to warfarin 1 week later. After 1 month, the patient presented to our clinic because of an episode of metrorrhagia, possibly due to warfarin. On examination, there was no jaundice, ascites or oedema, but the liver was enlarged. The patient had no previous history of liver disease and was not taking alcohol or any other medication except warfarin. Routine chemistries revealed: AST 442 IU/l, ALT 720 IU/l (normal <40 U/l), normal alkaline phosphatase and GGT, total bilirubin 0.8 mg/dl, serum albumin 4.2 g/dl, gammaglobulin 1.2 g/dl; prothrombin time 2.0 (INR ratio). Serology for hepatitis viruses A, B and C, cytomegalovirus, Epstein–Barr virus, herpes simplex virus and HIV was negative. Anti-nuclear, anti-actin and anti-LKM antibodies were negative. A repeated Doppler ultrasound excluded portal or hepatic vein thrombosis. Because the liver function tests persisted in the high range for more than 1 month, the patient underwent a liver biopsy after 5 days of warfarin interruption. Liver histology showed very mild inflammation in the portal tracts without lobular inflammation or cell damage (Fig. 1). Weakly eosinophilic and PAS positive vacuoles were seen in the hepatocytes. Stains for iron, copper, fibrinogen or alpha-1-antitrypsin deposits were negative. Eleven days after the liver biopsy, a reduction in LFTs was noted. Subcutaneous heparin was given after the biopsy and because of the suspicion of a drug-induced liver injury, oral anticoagulation was restarted with acenocoumarin rather than warfarin. LFTs continued to fall and normalised after about 45 days.