VENOCCLUSIVE DISEASE OF THE LIVER AFTER BONE-MARROW TRANSPLANTATION -THE ROLE OF HEMOSTASIS

Venocclusive disease of the liver is a relatively frequent early compl ication of bone marrow transplantation related to pre-transplant toxic injury to the liver. Events that lead to toxicity of the liver in the pre-transplant setting are infection, anti-neoplastic and anti-infect ious drug administration and radiation. The histological correlates of venocclusive disease are lesions mainly localized to structures in zo ne 3 of the liver acinus and in the sublobular central venules. At som e point in the pathogenesis of venocclusive disease, blood clotting an d inflammation occur. The first is characterized by laboratory signs o f coagulation activation, by an increase in several procoagulant prote ins and by a decrease in naturally occuring anticoagulants, particular ly protein C, the latter being a sensitive index of liver injury. Infl ammation is mediated by cytokine production, which maintains procoagul ant endothelial responses and liver injury. Severe venocclusive diseas e is associated with multi-organ failure and elevated mortality. Attem pts at finding predictive markers of the disease have succeeded in ide ntifying some coagulation and inflammatory proteins which can be usefu l in predicting the occurrence of VOD in selected patient groups. The role of hemostasis in venocclusive disease is underscored also by the reports on the successful prophylaxis and management of the disease wi th heparin and thrombolytic agents.