A 63 year old male patient had brain-stem infarction on the 7th of February. Treatment with heparin

Fråga: A 63 year old male patient had brain-stem infarction on the 7th of February. Treatment with heparin and warfarin were started the same day. Increased values of ASAT, ALAT, LD and amylase were observed. Treatment with heparin was discontinued on the 10th of February. ALAT was still increasing with maximal value 2.7. Maximal value for ASAT was 1.9, LD 14.8 and amylase 7.4. Warfarin was stopped on the 14th of February. Now the values of liver function are nearly normalised. Should this case be reported to the Swedish Adverse Drug Reaction Committee (SADRAC)? Could dicoumarol be used instead of warfarin in this case?

Sammanfattning: Heparin can probably cause a reversible cholestasis in rare occasions. There are reports showing that liver injury is a rare side effect of warfarin treatment. Documentation about liver damage and dicoumarol treatment is limited. If there is strong indication for anticoagulant treatment, dicoumarol can be tried when the liver function of the patient is monitored.

Svar: Liver damage caused by heparin is rare. Few cases have been reported where heparin caused moderate increase in aminotransferase levels (cf 1). According to the registration in SADRAC and some other cases, it has been judged that heparin can probably be the cause of a reversible cholestasis in rare occasions (1).

Hepatic injury caused by warfarin has been reviewed previously (2-5). As a summary, a few cases of liver damage have been reported with biochemical and histological evidence showing intrahepatic cholestasis (6-7). A new Medline search did not give more information. Six cases of liver damage after warfarin treatment have been reported to SADRAC where in 5 cases the connection was judged possible and in one case the connection can not be excluded.

Documentation concerning dicoumarol treatment and liver injury is scarce. This question was reviewed in (3) where only one article from 1958 was found reporting increased aminotransferases during dicoumarol treatment (cf 8). To SADRAC, two cases of aminotransferase elevation, one case of jaundice and one case of mixed bilirubin reaction after dicoumarol treatment were reported and the connections were judged probable or possible.

We recommend that this case should be reported to SADRAC. 1 Drugline nr 07527 (year 1990)
2 Drugline nr 07446 (year 1990)
3 Drugline nr 06156 (year 1988)
4 Drugline nr 04200 (year 1984)
5 Drugline nr 04162 (year 1984)
6 Jones DB, Makepeace MC, Smith PM: Jaundice following warfarin therapy. Postgrad Med J 1980; 56: 671
7 Rehnqvist N: Intrahepatic jaundice due to warfarin therapy. Acta Med Scand 1978; 204: 335-336

8 Stricker BHCH, Spoelstra P: Drug-induced hepatic injury. Ed by MNG Dukes. Elsevier, Amsterdam. 1985; pp 114-115