International journal of molecular medicine
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Civilian and military trauma patients consist of a disproportional number of young people, causing a considerable burden to society in terms of disability and premature death. Hemorrhage is a leading cause of mortality in this group of patients and the novel methods to reduce bleeding would be welcomed. Management of bleeding following major trauma includes hemostatic agents that offer effective clotting. ⋯ A recombinant PAI-1 with very long half-life developed in our laboratory (a two-point mutant, VLHL PAI-1, half-life over 700 h) has clinical potential as an agent to promote hemostasis in several scenarios including surgical injury, trauma, and PAI-1 deficiency. Here we report testing of VLHL PAI-1 as a potent inactivator of fibrinolysis reducing total blood loss while applied systemically or topically in experimental animals. The very long half-life of VLHL PAI-1 may provide an advantage in the important physiological mechanism to protect clots from premature dissolution, when applied topically or systemically to prevent excessive bleeding in the surgical and trauma setting and possibly in PAI-1 deficient patients.