LOW-MOLECULAR-WEIGHT HEPARIN FOR THE PREVENTION OF VENOOCCLUSIVE DISEASE OF THE LIVER IN BONE-MARROW TRANSPLANTATION PATIENTS

Hepatic veno-occlusive disease (VOD), a common complication of bone ma rrow transplantation (BRIT), is a result of intensive conditioning by chemo-radiotherapy. Endometrial injury causes fibrin deposition in the affected hepatic venules, leading to abnormal laboratory parameters f ollowed by often lethal full-blown disease. Previous studies have show n that unfractionated heparin can prevent VOD in BRIT patients. Since low molecular weight heparin (LMWH) preserves the antithrombotic, but not the anticoagulant, activity of unfractionated heparin, we initiate d a pilot study to determine the safety of LMWH for the prevention of VOD. Sixty-one patients undergoing BRIT (allogeneic, n=24; autologous, n=37) were randomized to receive subcutaneous injections of enoxapari n (40 mg/day x 1) or a placebo prior to BRIT conditioning and until da y 40 after transplantation or discharge from the hospital. LMWH admini stration did not influence marrow engraftment, nos was it associated w ith bleeding tendency. Hemorrhagic events occurred significantly less frequently (P=0.025) and were of shorter duration (P=0.006) in the LMW H group than in the placebo group. Time to platelet recovery was signi ficantly shorter (16.5 vs. 29.6 days, P=0.0075), and platelet transfus ion requirements were lower (P=0.05) in the LMWH patients. VOD paramet ers occurred less frequently in the experimental group, including dura tion of elevated bilirubin levels (P=0.01) and incidence of hepatomega ly (P=0.04). LMWH, which seems to enhance platelet recovery, may be sa fely administered to BRIT patients in an attempt to prevent VOD of the liver.