Complexing of tissue plasminogen activator with PAI-1, alpha 2-macroglobulin, and C1-inhibitor: studies in patients with defibrination and a fibrinolytic state after electroshock or complicated labor.
Release of tissue plasminogen activator (t-PA) and its interaction with plasma protease inhibitors were studied in two patients with massive defibrination, one after electroshock and soft tissue injury and the other after complicated labor; both had very severe hemorrhage. Large quantities of free t-PA were present in the circulation for several hours. Complexes of t-PA with plasminogen activator inhibitor 1 (PAI-1), alpha 2-macroglobulin and C1-inhibitor were also observed. PAI-1 antigen rose dramatically in both patients, and complexes of t-PA with PAI-1 rose rapidly during the period of observation. In contrast, the complexes of t-PA with alpha 2-macroglobulin and C1-inhibitor, present initially, persisted for short periods only and disappeared when free t-PA disappeared from the circulation. Plasmin was generated initially, as indicated by the presence of plasmin-alpha 2-antiplasmin complexes. Plasma concentrations of alpha 2-macroglobulin, C1-inhibitor, antithrombin III, and alpha 2-antiplasmin were severely depleted initially, but rapidly returned to normal. The observations demonstrate that there is a major release of t-PA in such defibrinating patients, that there is a role for protease inhibitors other than PAI-1 in the regulation of endogenous t-PA, and indicate the great rapidity with which such free t-PA is complexed and cleared.
Department of Medicine and Therapeutics, University of Aberdeen, Scotland, UK.
B
B
Bennett
A
A
Croll
K
K
Ferguson
N A
NA
Booth
D000328:Adult; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D004556:Electric Injuries / Q000097:blood*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D007744:Obstetric Labor Complications / Q000097:blood*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D003174:Complement C1 Inactivator Proteins; D015849:Plasminogen Inactivators; D000511:alpha-Macroglobulins; D010959:Tissue Plasminogen Activator