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
B Bennett, A Croll, K Ferguson and NA Booth
Department of Medicine and Therapeutics, University of Aberdeen, Scotland,
UK.
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.
Volume 75,
Issue 3,
pp. 671-676,
02/01/1990
Copyright © 1990 by The American Society of Hematology
