CHANGES IN PROTEIN-C, FACTOR-VII AND ENDOTHELIAL MARKERS AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION - POSSIBLE IMPLICATIONS IN THE PATHOGENESIS OF VENOOCCLUSIVE DISEASE

In a recent prospective study of allogenic bone marrow transplantation we reported that decreases in factor VII and protein C were predictiv e markers for high risk of veno-occlusive disease (VOD). In order to d etermine the relative involvement of endothelial and hepatocyte injury in the genesis of VOD, 34 consecutive patients undergoing autologous bone marrow transplantation (BMT) were studied. Conditioning was perfo rmed by chemotherapy alone or associated with total body irradiation ( TBI). Protein C and factor VII, the endothelial markers Von Willebrand factor (vWF and t-PA, fibrinogen and fibronectin were measured weekly before and after BMT. Protein C and factor VII were within the normal range before BMT, decreased significantly on day 7 to 73 and 64% resp ectively (p < .01) and then returned to normal values. Fibrinogen incr eased to 7 g/l (p < .001) on day 7 but then returned to normal levels. Fibronectin was abnormally high (p < .001) before BMT and decreased t hereafter, while vWF increased (p < 0.001) for three consecutive weeks . t-PA was low (p < 0.001) before conditioning but increased thereafte r. These results demonstrate the presence of endothelial lesions befor e BMT and acute hepatic and endothelial lesions after conditioning. Al though VOD was never observed in our patients, this complication could well arise from preexisting vascular lesions due to previous chemothe rapy and/or from acute hepatocytic injury, which could also be of endo thelial origin, after conditioning.