INCREASED LEVELS OF TISSUE PLASMINOGEN-ACTIVATOR (T-PA) AND TISSUE PLASMINOGEN-ACTIVATOR INHIBITOR (PAI) CORRELATE WITH TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA)-RELEASE IN PATIENTS SUFFERING FROM MICROANGIOPATHY FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION (BMT)

Severe microangiopathy resembling thrombotic thrombocytopenic purpura (TTP) has been reported as a complication of acute graft-versus-host disease (aGvHD) in patients receiving Ciclosporin (CsA) prophylaxis following allogeneic BMT. In order to analyze the pathophysiological events involved in microangiopathy, a prospective study comparing release of von Willebrand Factor (vWF), t-PA and PAI, as well as TNF-alpha and further coagulation parameters was performed in 32 patients. Endothelial damage as the central lesion was confirmed by the close association of vWF and t-PA:Antigen with severity of microangiopathy. t-PA activity, however, was neutralized by a simultaneous rise in PAI. Activation of coagulation in the course of microangiopathy was further confirmed by increased levels of DDimer (DDi), fibrinopeptide A (FPA), beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). As clinical grades of microangiopathy, as well as the release of t-PA:Ag and PAI were correlated with systemic release of TNF-alpha our data further support our hypothesis of cytokine induced endothelial damage in clinical complications following allogeneic BMT.