HYPERCOAGULABILITY IN PATIENTS WITH VENOO CCLUSIVE DISEASE AFTER BONE-MARROW TRANSPLANTATION

Background: Veno-occlusive disease (VOD) leads to obliteration of smal l intrahepatic venules and is one of three most important complication s with fatal outcome after bone marrow transplantation (BMT). The etio logy of VOD is not completely understood. Endothelial cell injury indu ced by the conditioning myeloablative radiochemotherapy with subsequen t activation of the coagulation cascade seems to be a crucial step in the pathogenesis of the disease. Patients and Methods: We investigated tissue plasminogen activator (tPA), its main inhibitor (PAI-1) and th e natural anticoagulants protein C and S by enzymimmunoassay prospecti vely in 32 bone marrow transplant recipients. Results: VOD developed i n four patients. They presented with extremely elevated levels of PAI- 1 after BMT whereas tPA levels remained low. Additionally a transient decrease of protein S was found one week after BMT which was more pron ounced in VOD patients. No protein C deficiency was observed. Conclusi on: Our data suggest that hypofibrinolysis due to an excess of PAI-1 m ay be involved in the pathogenesis of VOD. The determination of PAI-1 may be useful to recognize the development of VOD and facilitate the d ecision for thrombolytic therapy with rtPA. A decrease of protein S ma y play a role as a cofactor in the early phase after BMT.