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

- The contributions of platelets and fibrinogen to early TIC are not well understood.
- We report an early hypocoagulopathy in a rat model of severe hemorrhagic shock.
- ROTEM indicated a platelet defect after the bleed and fibrinogen defect after shock.
- Platelet/fibrinogen ratio appeared to be regulated despite a worsening coagulopathy.
- The underlying platelet/fibrinogen defect mechanisms to coagulopathy are not known.

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 20 min and animals were left in shock 60 min. 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 20 min 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 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 ~ 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.