Hayley L Letson1, Geoffrey P Dobson2. 1. 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. 2. 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.
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.
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: Leasha J Schaub; Hunter B Moore; Andrew P Cap; Jacob J Glaser; Ernest E Moore; Forest R Sheppard Journal: J Trauma Acute Care Surg Date: 2017-03 Impact factor: 3.313
Authors: Derek J B Kleinveld; Pieter H Sloos; Femke Noorman; M Adrie W Maas; Jesper Kers; Tim W H Rijnhout; Margreet Zoodsma; Rigo Hoencamp; Markus W Hollmann; Nicole P Juffermans Journal: Transfusion Date: 2020-06-27 Impact factor: 3.157