Differential contributions of platelets and fibrinogen to early coagulopathy in a rat model of hemorrhagic shock

Journal Publication ResearchOnline@JCU
Letson, Hayley L.;Dobson, Geoffrey
Abstract

Background: The mechanisms of early traumatic-induced coagulopathy are not well understood. Our aim was to examine the role of platelets and fibrinogen to early coagulopathy in the rat after hemorrhagic shock. Methods: Adult Sprague-Dawley rats were anesthetized and randomly assigned to: 1) Baseline, 2) Hemorrhage or 3) Shock (n = 10 each). Controlled phlebotomy occurred over 20 min and animals were left in shock 60 min. Coagulation was assessed using PT, aPTT, ROTEM and ELISAs. Results: PT and aPTT increased 5 to 7 times following hemorrhage and shock. Prolongation of EXTEM and INTEM clotting times, lower clot elasticity and increased EXTEM lysis index (LI) indicated a hypocoagulopathy. After 20 min hemorrhage, LI(30-60) in FIBTEM was similar to 100%, EXTEM 83-87% and APTEM 80-82% indicating a platelet contribution to the coagulopathy with no hyperfibrinolysis. After 60 min shock, the situation was reversed with fibrinogen loss being a contributor. This apparent switch from a platelet-to a fibrinogen-based coagulopathy, with fibrinolysis, was supported by >= 15% in maximum lysis (ML), a threefold increase in plasma PAI-1 after hemorrhage, and undetectable levels after shock. Curiously, the relative contribution of fibrinogen/platelet ratio to clot amplitude, determined from FIBTEM/EXTEM A10 ratio (and MCF), remained unchanged at similar to 1:5 for baseline, hemorrhage and shock despite a progressive hypocoagulopathy. Significant increases in P-selectin, acidosis and lactate indicated systemic endothelial damage and tissue hypoperfusion. Conclusions: Hypocoagulopathy following severe hemorrhage and shock in the rat appeared to involve a two-step process of platelet dysfunction followed by fibrinogen impairment, possibly linked to progressive endothelial dysfunction.

Journal

Thrombosis Research

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141

ISBN/ISSN

1879-2472

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Pages Count

8

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Publisher

Elsevier

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DOI

10.1016/j.thromres.2016.03.007