World Journal of Trauma and Critical Care Medicine Volume No 8

Review Open Access

Trauma induced coagulopathy

* Naoki Hashimoto

  • *Kindai University, School of Medicine, Ohno-Higashi Osaka-Sayama, Osaka 589-8511 Japan
  • Submitted: Thursday, August 4, 2016
  • Accepted: Sunday, August 21, 2016
  • Published: Monday, August 22, 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited


Coagulopathy is frequently present in trauma. Acute coagulopathy associated with trauma (ACoT) has been recognized as a distinct entity associated with increased mortality, morbidity and transfusion requirements.

Uncontrolled bleeding is the most frequent preventable cause of death in trauma patients reaching hospital alive. Coagulopathy in trauma has been long thought to develop as a result of hemodilution, acidosis and hypothermia often related to resuscitation practices. The lack of well defined diagnosis criteria for ACoT impedes early identification and treatment. Prolongation of prothrombin time (PT) and activated thromboplastine time (APTT) have been used by most author to diagnosis ACoT. Mechanisms contributing to ACoT include anticoagulation, consumption, platelet dysfunction and hyperfibrinolysis. Early administration of tranexamic acid, recombinant factor VII and aggressive blood product transfusional management for ACoT with a red blood cell: plasma: platelets ratio close to 1:1:1 could result in decreased mortality from uncontrolled bleeding. This article reviews the pathophysiology and management of ACoT.

Key words:

Acute coagulopathy associated with trauma (ACoT); tranexamic acid; recombinant factor VII


Trauma remains a leading cause of death and disability in adults in spite of advances in resuscitation, surgical management, and critical care [1]. From 25 to 35% of injured civilian trauma patients develop a biochemically evident coagulopathy when they arrived at emergency department, though there are improved efficiency of trauma system and reducing the time interval between acute injury and treatment [2]. Coagulopathy may be the result of physiologic derangements such as acidosis, hypothermia or hemodilution related to fluid or blood administration. The etiology, diagnosis and treatment, the pathophysiology and management of acute coagulopathy of trauma (ACoT) is reviewed in this article.


Injury to brain tissue may predispose to acute traumatic coagulopathy and about one-third of patients with traumatic brain injury (TBI) have a coagulopathy, although whether TBI-associated coagulopathy is fundamentally different from injury-related coagulopathy is not yet clearly understood [3].


The precise physiopathology of acute coagulopathy of trauma (ACoT) is still unclear, but likely multifactorial and related to the severity of trauma and degree of shock, given the higher incidence with increasing injury severity score (ISS). Two main mechanisms have been proposed. The first is the activation of protein C (APC) secondary to hypoperfusion due to massive bleeding. APC inactivates factor VII and V and increases fibrinolysis due to consumption of antifibrinolytics. Increased fibrinolysis is enhanced by the release of tissue plasminogen activator (tPA) secondary to tissue damage. The second mechanism poses that endothelial damage and tissue factor exposure generate disseminated intravascular coagulation (DIC) with subsequent increase in thrombin generation, microthrombosis, and consumption of coagulation factors [4]. Regardless of the initial mechanisms of ACoT, coagulopathy will continue to worsen if hemodilution, acidosis, and hypothermia develop due to an inadequate treatment [5].


Acidosis causes clotting dysfunction in experimental model at pH<7.2 by interfering with the assembly of coagulation factor complexes involving calcium and negatively-charged phospholipids [6]. As an example, the activity of the factor Xa/Va/phospholipid/prothrombin complex is reduced by 50, 70, and 90% at a pH of 7.2, 7.0 and 6.8 respectively. However, correction of acidosis alone does not correct the coagulopathy, because injury causes coagulopathy via additional mechanism [7].


Hypothermia in injured patients is graded into mild (36 to 34°C,moderate (34 to 32 °C)and sever (<32°C) [8]. Most of trauma patients have a temperature below 36°C on arrival at emergency hospital.9% of trauma patients have a temperature below 33°C [9].he effect of hypothermia on clotting includes platelet dysfunction and impaired enzymatic function. Overall thrombin generation in activated in vitro clotting systems is generally preserved at a temperature of 33°C; however, impairment of tissue factor activity, platelet aggregation, and platelet adhesion are evident at temperatures between 33 to 37°C [10].

Dilution coagulopathy

A retrospective study of 8724 injured patients from the German Trauma Registry found a positive correlation between prehospital fluid resuscitation volume and coagulopathy [11]. Frequency of coagulopathy was more than 50% when they are received>3L of intravenous fluid prior to arrival, but that of coagulopathy was also present in 10% of patients administered <500ml. Another factor contributing to coagulopathy is the effect of shelf time on packed red blood cells which undergo progressive functional and structural changes over time. The shelf life includes decreased pH, decreased of calcium, low 2,3 diphosphoglycerate levels, and decreasing clotting factor concentration.


Prolongation of prothrombin time (PT) and activated thromboplastin time (APTT) have been used by most authors to diagnose ACoT. Bronhi et al., established the presence of ACoT if PT and APTT were 1.5 times over the normal values [2] The prevalence of prolonged PT is higher, but prolongation of the PTT is more specific.

While these tests are simple and widely available, they have several limitations. PT and APTT reflect hemostasis in plasma during the first 60 seconds of clotting. Moreover, these tests have a turnaround time of 35-45 minutes, are carried out at 37°C and pH 7.5, and do not consider the presence of hypothermia, acidosis, hypocalcium and anemia. Therefore, the use of devices which we can measure the value of PT and APTT for short time has been proposed.

Decrease platelet count and decreased platelet function also contribute to coagulopathy and poor outcome following trauma, although little information about platelet function is evident from the platelet count alone. Thromboelastography (TEG) and rotation thromboelastometry (ROTEM) to diagnose ACoT has been proposed, since both techniques allow complete evaluation of coagulation (beginning, speed and extent of the clot formation) and fibrinolysis. A positive correlation between TEG, ROTEM and traditional coagulation tests (PT, APTT, INR) has been reported.


Tranexamic acid (TXA)

The most studied antifibrinolytic has been tranexamic acid (TXA). TXA inhibits plasminogen activation, as well as plasmin activity, preventing fibrin clot lysis. The CRASH-2 study [13] evaluated the use of TXA versus placebo in trauma within 8 hours of injury. This was a multicenter RCT that recruited more than 20000 trauma patients with hemodynamic compromise or at risk of significant bleeding. The study showed that the use of TXA was associated with a decrease in mortality and deaths resulting from bleeding, without an increase in thrombotic complications. Based on the key role of hyperfibrinolysis in ACoT pathogenesis and the results of CRASH-2, several authors have proposed that the use of TXA should be a standard in trauma management [14].

Recombinant factor VIIa

Two RCTs have evaluated the use of activated factor VII (rF VIIa) in trauma. This agent was developed for the treatment of hemophilia A or B. Recently, the control study [15], was performed to compare rF VIIa to placebo. This trial found a decrease in transfusion requirement but no mortality difference. Given these results and its elevated cost,rF VIIa is currently recommended only as a final option in controlling massive bleeding in blunt trauma ( after surgery, interventional procedures and blood transfusion) [16]. This drug has been used at the R Adams Cowley Shock Trauma Center (STC) in Baltimore since 2001. 2 doses are used at STC. The higher dose (100μg/kg) is suitable for patients in shock with active ongoing hemorrhage. The smaller dose (50μg/kg) is used for patients who are not in shock but still have life-threatening hemorrhage and coagulopathy. The typical patient is elderly, is receiving warfarin therapy, and has intracranial hemorrhage after traumatic brain injury.Red blood cell: plasma: platelets ratio

Determining an appropriate fluid resuscitation technique during trauma induced coagulopathy in challenging. The addition of crystalloid or nonblood colloids with further exacerbates a tenuous situation [17]. We advocate a balanced administration of RBC, plasma and platelets (1:1:1) for massive resuscitation. This is the closest representation of whole blood administration and provides maximal resuscitation while maintain the ability for clot formation. US military data from operation Iraqi Freedom tend to support this review [18].


Coagulopathy is frequent present in trauma. Acute coagulopathy associated with trauma (ACoT) has been recognized as a distinct entity associated with increased mortality, morbidity and transfusion requirements.

Uncontrolled bleeding is the most frequent preventable cause of death in trauma patients reaching hospital alive. Early correction of ACoT through damage control resuscitation is a promising treatment for preventable trauma death. Early administration of tranexamic acid, recombinant factor VII and aggressive blood product transfusional management for ACoT with a red blood cell: plasma: platelets ratio close to 1:1:1 could result in decreased mortality from uncontrolled bleeding.

Authors' contribution

NH conceived and designed the study prepared the manuscript

Conflict of Interests

The author declare that there is no conflict of interests


None Declared


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