Activation of coagulation and fibrinolysis following OKT3 administration to renal transplant recipients: association with distinct mediators.
Treatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels were increased as compared to pretreatment levels (p less than 0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels increased only at 15 min. In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release.
D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D003165:Complement System Proteins / Q000187:drug effects*; D016207:Cytokines / Q000097:blood*; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D010447:Peptide Hydrolases / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D016207:Cytokines; D016853:Muromonab-CD3; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; C046193:antithrombin III-protease complex; C024668:plasmin-alpha(2)-macroglobulin complex; D000990:Antithrombin III; D003165:Complement System Proteins; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D008775:Methylprednisolone