Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans

J Neurotrauma. 2014 Feb 15;31(4):404-10. doi: 10.1089/neu.2013.3089. Epub 2013 Nov 21.


Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adenosine Diphosphate / pharmacology
  • Animals
  • Blood Cell Count
  • Blood Coagulation Disorders / blood*
  • Blood Coagulation Disorders / etiology
  • Blood Coagulation Disorders / pathology
  • Blood Platelets / drug effects*
  • Brain / pathology
  • Brain Injuries / blood*
  • Brain Injuries / complications
  • Brain Injuries / pathology
  • Hirudins / pharmacology
  • Kinetics
  • Male
  • Partial Thromboplastin Time
  • Platelet Aggregation / physiology
  • Prothrombin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Subarachnoid Hemorrhage / blood
  • Thrombelastography
  • Thrombin / antagonists & inhibitors
  • Wounds, Nonpenetrating / blood*
  • Wounds, Nonpenetrating / pathology


  • Hirudins
  • Recombinant Proteins
  • Adenosine Diphosphate
  • Prothrombin
  • Thrombin
  • lepirudin