• Thrombosis research · May 2016

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

    • Hayley L Letson and Geoffrey P Dobson.
    • Heart, Trauma and Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Queensland 4811, Australia. Electronic address: hayley.letson@jcu.edu.au.
    • Thromb. Res. 2016 May 1; 141: 58-65.

    BackgroundThe 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.MethodsAdult Sprague-Dawley rats were anesthetized and randomly assigned to: 1) Baseline, 2) Hemorrhage or 3) Shock (n=10 each). Controlled phlebotomy occurred over 20min and animals were left in shock 60min. Coagulation was assessed using PT, aPTT, ROTEM and ELISAs.ResultsPT 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 20min hemorrhage, LI(30-60) in FIBTEM was ~100%, EXTEM 83-87% and APTEM 80-82% indicating a platelet contribution to the coagulopathy with no hyperfibrinolysis. After 60min 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 ~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.ConclusionsHypocoagulopathy 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.Copyright © 2016 Elsevier Ltd. All rights reserved.

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