Hemostatic defects in massive transfusion: an update and treatment recommendations

ABSTRACT

Introduction

Acute hemorrhage is a global healthcare issue, and remains the leading preventable cause of death in trauma. Acute severe hemorrhage can be related to traumatic, peripartum, gastrointestinal, and procedural causes. Hemostatic defects occur early in patients requiring massive transfusion. Early recognition and treatment of hemorrhage and hemostatic defects are required to save lives and to achieve optimal patient outcomes.

Areas covered

This review discusses current evidence and trials aimed at identifying the optimal treatment for hemostatic defects in hemorrhage and massive transfusion. Literature search included PubMed and Embase.

Expert opinion

Patients with acute hemorrhage requiring massive transfusion commonly develop coagulopathy due to specific hemostatic defects, and accurate diagnosis and prompt correction are required for definitive hemorrhage control. Damage control resuscitation and massive transfusion protocols are optimal initial treatment strategies, followed by goal-directed individualized resuscitation using real-time coagulation monitoring. Distinct phenotypes exist in trauma-induced coagulopathy, including ‘Bleeding’ or ‘Thrombotic’ phenotypes, and hyperfibrinolysis vs. fibrinolysis shutdown. The trauma ‘lethal triad’ (hypothermia, coagulopathy, acidosis) has been updated to the ‘lethal diamond’ (including hypocalcemia). A number of controversies in optimal management exist, including whole blood vs. component therapy, use of factor concentrates vs. blood products, optimal use of tranexamic acid, and prehospital plasma and tranexamic acid administration.

KEYWORDS:

• Hemorrhage
• massive transfusion
• massive transfusion protocol
• hemostasis
• hemostatic defects
• coagulopathy
• trauma-induced coagulopathy
• damage control resuscitation
• goal-directed hemostatic resuscitation
• fibrinolysis
• tranexamic acid
• fibrinogen concentrate
• prothrombin complex concentrate

Article highlights

• Hemorrhage is a leading cause of death in severe bleeding due to many conditions, including trauma, peripartum hemorrhage, surgery/procedures, and gastrointestinal bleeding

• Trauma-induced coagulopathy (TIC) results from both acute trauma coagulopathy (ATC) related to tissue injury and shock which occurs immediately and resuscitation coagulopathy (RC) related to fluid/blood product resuscitation, hypothermia, acidosis and hypocalcemia.

• ATC is thought, in part, related to systemic endothelial damage or endotheliopathy (shock-induced endotheliopathy, SHINE), due to the host inflammatory response and sympathoadrenal activation in response to tissue injury and hemorrhage.

• Distinct phenotypes exist in TIC, including ‘Bleeding’ or ‘Thrombotic’ phenotypes

• Distinct fibrinolysis phenotypes exist in TIC, including hyperfibrinolysis, normal, and fibrinolysis shutdown, with both abnormal phenotypes associated with higher mortality

• Viscoelastic testing (ROTEM, TEG) is required to determine fibrinolytic phenotype in TIC: physiologic, hyperfibrinolysis or fibrinolysis shutdown

• Initial management of severe bleeding requires early massive transfusion protocol (MTP) use and damage control resuscitation (DCR)

• The ‘lethal diamond’ of hypothermia, acidosis, coagulopathy, and hypocalcemia should be prevented and/or treated as part of MTP

• Early aggressive calcium repletion should be part of MTP to prevent hypocalcemia

• Tranexamic acid should be administered to trauma patients with hemorrhagic shock who are within 3 hours of injury or have evidence of hyperfibrinolysis.

• Prehospital plasma resuscitation reduces mortality in traumatic hemorrhage with prolonged transport times to definitive trauma care

• In patients with hypofibrinogenemia, fibrinogen concentrate is emerging as an alternative therapy to cryoprecipitate or plasma

• Some studies support the early use of factor concentrates (fibrinogen concentrate, prothrombin complex concentrate) for TIC treatment in trauma hemorrhage, but additional multicenter randomized trials are required to validate this.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.