Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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). 141 3

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.
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PMID:Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. 957 11