Summary:This retrospective cohort study of 462 consecutive adult allogeneic and autologous blood or marrow transplantation (BMT) patients compared the incidence of hepatic veno-occlusive disease (VOD) after BMT with three prophylactic regimens. Patients receiving heparin (Hep), heparin + prostaglandin E1 (Hep + PGE1) or low molecular weight heparin (LMWH) as a prophylactic VOD regimen were compared to a historical cohort receiving no VOD prophylaxis. Of 462 BMT patients, VOD was diagnosed in 22% (31 of 142) of the no prophylaxis group, 11% (11 of 104) of the Hep, 12% (13 of 110) in the Hep + PGE1 and 4% (four of 106) of the LMWH group (P = 0.0002). VOD was the primary cause of death in 20% (12 of 59). By multivariate logistic regression, independent risk factors for developing VOD were: no VOD prophylactic regimen, unrelated allogeneic BMT, Karnofsky performance score (KPS) Ͻ80 and aspartate aminotransferase (AST) у50 U/l. There was no increase in the rate of death due to hemorrhagic events or VOD in any prophylaxis group compared to the control group. Prospective randomized trials of Hep vs LMWH vs placebo are warranted to assess the efficacy of heparin compounds in the prevention of VOD. Bone Marrow Transplantation (2001) 27, 627-633. Keywords: veno-occlusive disease; prophylaxis; heparin; blood and marrow transplantation Veno-occlusive disease (VOD) of the liver is a clinical syndrome, characterized by hyperbilirubinemia, painful hepatomegaly and fluid retention. 1 It occurs in up to 54% of patients and is a leading cause of blood or marrow transplantation (BMT)-related death with a mortality rate up to 3 The etiology of VOD is not clearly defined, however, drug-induced hepatocellular damage occurs in the centrilobular zones of the liver. The coagulation cascade may have a role in VOD pathophysiology due to clotting factor activation leading to fibrin deposition in the central veins. It has been postulated that anticoagulant therapy could prevent fibrin deposition and subsequent hepatic damage. 5,6 Several clinical trials of prophylactic heparin (Hep) during BMT have shown contradictory results. [7][8][9][10][11][12] Nevertheless, these studies demonstrated that low doses of Hep could be safely administered to BMT patients. Prostaglandin E1 (PGE1) was used as a VOD prophylactic regimen by Gluckman et al, 13 who found a decreased incidence of VOD in patients treated with PGE1, whereas Bearman et al, 14 concluded that PGE1 was too toxic. Previous work has demonstrated the efficacy and safety of low molecular weight heparin (LMWH) for deep venous thrombosis prophylaxis and treatment. 15,16 A small prospective study comparing LMWH to placebo revealed a shorter duration of VOD-related symptoms after BMT in the LMWH treated patients. 17 In our retrospective study, we analyzed three VOD prophylactic regimens in 462 patients undergoing allogeneic or autologous BMT. The VOD preventive effects of Hep, Hep + PGE1 and LMWH were compared to each other and to a historical control group. This is the first retrospective mul...