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Very long half‐life plasminogen activator inhibitor type 1 reduces bleeding in a mouse model
Author(s) -
Jankun Jerzy,
Selman Steven H.,
Keck Rick W.,
ŁysiakSzydłowska Wiesława,
SkrzypczakJankun Ewa
Publication year - 2010
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2009.08962.x
Subject(s) - fibrinolysis , fibrin , plasminogen activator , plasminogen activator inhibitor 1 , thromboelastometry , bleeding time , coagulation , chemistry , pharmacology , tissue plasminogen activator , whole blood , in vivo , medicine , immunology , platelet , biology , platelet aggregation , microbiology and biotechnology
OBJECTIVE To investigate the potential for the future clinical use of a very long half‐life plasminogen activator inhibitor type 1 (VLHL PAI‐1) as a haemostatic agent. MATERIALS AND METHODS We developed a VLHL PAI‐1 (half‐life >700 h) recombinant mutant of PAI‐1 and assessed VLHL PAI‐1 for its ability to inhibit fibrinolysis in vitro using human, rabbit, mouse and rat blood. Fibrin clot lysis time, monitored by thromboelastometry, was determined at various concentrations of VLHL PAI‐1. Also, we determined total bleeding time and total blood loss of control, VLHL PAI‐1‐, tissue‐type plasminogen activator (tPA)‐ and tPA + VLHL PAI‐1‐treated mice. RESULTS Using a thromboelastometer, mouse blood was most similar to human blood in its coagulation and fibrinolytic characteristics. We evaluated the affect of VLHL PAI‐1 on haemostasis using the mouse model and showed that VLHL PAI‐1 is an effective inhibitor of fibrin clot degradation. It reduced time of bleeding and total blood loss. CONCLUSION VLHL PAI‐1 may provide an important physiological mechanism to protect clots from premature dissolution in surgical and trauma settings.