title: Differential contributions of platelets and fibrinogen to early coagulopathy in a rat model of hemorrhagic shock.
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 20min and animals were left in shock 60min. 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 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Letson
authors.affiliation: 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: geoffrey.dobson@jcu.edu.au.
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Dobson
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013916:Thrombelastography
chemical_list: D005340:Fibrinogen
keywords: Coagulopathy; Fibrinogen; Hemorrhage; Platelets; ROTEM; Shock