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 cyclosporin (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.
Seeber
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Medizinische Klinik III, Ludwig-Maximilians-Universität München, FRG.
Hiller
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Holler
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Kolb
H J
HJ
D000208:Acute Disease; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005169:Factor VIII / Q000032:analysis; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006086:Graft vs Host Disease / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008833:Microcirculation; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D010978:Platelet Factor 4 / Q000032:analysis; D011446:Prospective Studies; D012720:Severity of Illness Index; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014652:Vascular Diseases / Q000097:blood*; D001620:beta-Thromboglobulin / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D001620:beta-Thromboglobulin; C036309:fibrin fragment D; D014841:von Willebrand Factor; D010978:Platelet Factor 4; D016572:Cyclosporine; D005169:Factor VIII; D010959:Tissue Plasminogen Activator