What are adjuncts to massive transfusion for the control of hemorrhage?

Updated: Apr 16, 2019
  • Author: Linda L Maerz, MD, FACS, FCCM; Chief Editor: Emmanuel C Besa, MD  more...
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Adjuncts for the control of massive hemorrhage have been investigated and utilized over the course of the past two decades.  Recombinant activated factor VII (rFVIIa) is synthesized human factor VII and has typically been used to treat hemophilia and other congenital and acquired coagulopathies. More recently, in the first decade of this millennium, rFVIIa was increasingly used in patients with active hemorrhage and coagulopathy from trauma, traumatic brain injury, excessive warfarin use, and other acquired hematologic defects, including acquired factor inhibitors. [29, 30, 31, 32] The early studies in trauma patients demonstrated a decrease in RBC requirement and a trend toward improved survivorship.  Subsequently, the CONTROL trial published in 2010 was a prospective, randomized, double-blinded, multicenter placebo controlled trial, designed as a phase 3 trial of rFVIIa in severely injured trauma patients with life-threatening bleeding.  Although rFVIIa reduced blood product use, mortality was not affected, and enthusiasm for its use in the trauma population has waned. [33]

The utilization of antifibrinolytic agents as adjuncts in the management of severe traumatic hemorrhage is plausible because primary fibrinolysis is a key component in the pathophysiology of the acute coagulopathy of trauma.  The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH)-2 (published in 2010) and Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) (published in 2012) trials are key studies that demonstrated improved mortality associated with the administration of the antifibrinolytic agent tranexamic acid (TXA) in civilian and military trauma, respectively.  TXA administration is associated with a reduction in 28-day all-cause mortality in adult trauma patients with signs of bleeding (systolic blood pressure < 90 mm Hg, heart rate > 110 beats/minute, or both).  TXA has the greatest impact on death reduction in severe shock (systolic blood pressure ≤ 75 mm Hg).  Early TXA (≤ 1 hour after injury) results in the greatest bleeding-related death reduction.  TXA administered 1-3 hours following injury also reduces bleeding-related death, but to a lesser degree.  TXA administered > 3 hours after injury has been associated with an increased risk of death due to bleeding.  Therefore, current recommendations for the use of TXA in trauma include:  1) administration to adult trauma patients with severe hemorrhagic shock (SBP ≤ 75 mm Hg), with known predictors of fibrinolysis, or with established fibrinolysis via TEG (LY > 3%); 2) administration only if < 3 hours after injury; and 3) dosing of 1 gram intravenously (IV) over 10 minutes followed by 1 gram IV over 8 hours. [34, 35, 36, 37]

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