Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients

Hepatic veno-occlusive disease (VOD), a common complication of bone marrow transplantation (BMT), is a result of intensive conditioning by chemo- radiotherapy. Endometrial injury causes fibrin deposition in the affected hepatic venules, leading to abnormal laboratory parameters followed by often lethal full-blown disease. Previous studies have shown that unfractionated heparin can prevent VOD in BMT patients. Since low molecular weight heparin (LMWH) preserves the antithrombotic, but not the anticoagulant, activity of unfractionated heparin, we initiated a pilot study to determine the safety of LMWH for the prevention of VOD. Sixty-one patients undergoing BMT (allogeneic, n=24; autologous, n=37) were randomized to receive subcutaneous injections of enoxaparin (40 mg/day x 1) or a placebo prior to BMT conditioning and until day 40 after transplantation or discharge from the hospital. LMWH administration did not influence marrow engraftment, nor was it associated with bleeding tendency. Hemorrhagic events occurred significantly less frequently (P=0.025) and were of shorter duration (P=0.006) in the LMWH group than in the placebo group. Time to platelet recovery was significantly shorter (16.5 vs. 29.6 days, P=0.0075), and platelet transfusion requirements were lower (P=0.05) in the LMWH patients. VOD parameters occurred less frequently in the experimental group, including duration of elevated bilirubin levels (P=0.01) and incidence of hepatomegaly (P=0.04). LMWH, which seems to enhance platelet recovery, may be safely administered to BMT patients in an attempt to prevent VOD of the liver.