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Am J Physiol Regul Integr Comp Physiol. 2016 Feb 15;310(4):R323-9. doi: 10.1152/ajpregu.00401.2015. Epub 2015 Dec 2.

Procoagulant and fibrinolytic activity after polytrauma in rat.

Author information

1
Blood Research, United States Army Institute of Surgical Research, Fort Sam Houston, Texas; and the Department of Surgery, University of Texas Health Science Center, San Antonio, Texas xiaowu.wu.civ@mail.mil.
2
Blood Research, United States Army Institute of Surgical Research, Fort Sam Houston, Texas; and the Department of Surgery, University of Texas Health Science Center, San Antonio, Texas.

Abstract

The purpose of this study was to determine whether trauma-induced coagulopathy is due to changes in 1) thrombin activity, 2) plasmin activity, and/or 3) factors that stimulate or inhibit thrombin or plasmin. Sprague-Dawley rats were anesthetized with 1-2% isoflurane/100% oxygen, and their left femoral artery and vein were cannulated. Polytrauma included right femur fracture, and damage to the small intestines, the left and medial liver lobes, and right leg skeletal muscle. Rats were then bled 40% of blood volume. Plasma samples were taken before trauma, and at 30, 60, 120, and 240 min. Polytrauma and hemorrhage led to a significant fall in prothrombin levels. However, circulating thrombin activity did not change significantly over time. Antithrombin III and α2 macroglobulin fell significantly by 2 h, then rose by 4 h. Soluble thrombomodulin was significantly elevated over the 4 h. Circulating plasmin activity, plasminogen, and D-dimers were elevated for the entire 4 h. Tissue plasminogen activator (tPA) was elevated at 30 min, then decreased below baseline levels after 1 h. Plasminogen activator inhibitor-1 was significantly elevated at 2-4 h. Neither tissue factor pathway inhibitor nor thrombin activatable fibrinolysis inhibitor changed significantly over time. The levels of prothrombin and plasminogen were 30-100 times higher than their respective active enzymes. Polytrauma and hemorrhage in rats lead to a fibrinolytic coagulopathy, as demonstrated by an elevation in plasmin activity, D-dimers, and tPA. These results are consistent with the observed clinical benefit of tranexamic acid in trauma patients.

KEYWORDS:

coagulation; fibrinolysis; hemorrhage; plasmin; thrombin

PMID:
26632604
PMCID:
PMC4796743
DOI:
10.1152/ajpregu.00401.2015
[Indexed for MEDLINE]
Free PMC Article

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