Background: Traumatic coagulopathy is thought to be caused primarily by fluid administration and hypothermia. Methods: A retrospective study was performed to determine whether coagulopathy resulting from the injury itself is a clinically important entity in severely injured patients. Results: One thousand eight hundred sixty-seven consecutive trauma patients were reviewed, of whom 1,088 had full data sets. Median Injury Severity Score was 20, and 57.7% had an Injury Severity Score > 15; 24.4% of patients had a significant coagulopathy. Patients with an acute coagulopathy had significantly higher mortality (46.0% vs. 10.9%;θ²,p< 0.001). The incidence of coagulopathy increased with severity of injury, but was not related to the volume of intravenous fluid administered (r² = 0.25,p< 0.001). Conclusion: There is a common and clinically important acute traumatic coagulopathy that is not related to fluid administration. This is a marker of injury severity and is related to mortality. A coagulation screen is an important early test in severely injured patients.

Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors. Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion, and investigated derangements in coagulation associated with this. This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1+2, fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and d-dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion. A total of 208 patients were enrolled. Patients without tissue hypoperfusion were not coagulopathic, irrespective of the amount of thrombin generated. Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD. An increasing BD was associated with high soluble thrombomodulin and low protein C levels. Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high d-dimer levels. High thrombomodulin and low protein C levels were significantly associated with increased mortality, blood transfusion requirements, acute renal injury, and reduced ventilator-free days. Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.

Background: Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock. Methods: This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1 + 2 (PF1 + 2), fibrinogen, factor VII, thrombomodulin, protein C, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), and D-dimers. Base deficit was used as a measure of tissue hypoperfusion. Results: Two hundred eight patients were studied. Systemic hypoperfusion was associated with anticoagulation and hyperfibrinolysis. Coagulation was activated and thrombin generation was related to injury severity, but acidosis did not affect Factor VII or PF1 + 2 levels. Hypoperfusion-induced increase in soluble thrombomodulin levels was associated with reduced fibrinogen utilization, reduction in protein C and an increase in TAFI. Hypoperfusion also resulted in hyperfibrinolysis, with raised tPA and D-Dimers, associated with the observed reduction in PAI-1 and not alterations in TAFI. Conclusions: Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.

Summary. Background: Low fibrinogen levels are known to occur in trauma. However, the extent of fibrinogen depletion during trauma hemorrhage, the response to replacement therapy and association with patient outcomes remain unclear. Objectives: The study aims were to: characterize admission fibrinogen level and correlate it with factors associated with injury; describe the time course of fibrinogen depletion and response to replacement therapy; determine the correlation of fibrinogen level with rotational thromboelastography (ROTEM) parameters; evaluate the effect of fibrinogen supplementation ex vivo; and establish the association between fibrinogen level and clinical outcomes. Methods: This was a prospective cohort study of 517 patients. Blood samples were drawn on admission and after admistration of every 4 units of packed red blood cells. Fibrinogen levels were determined with the Clauss method, and global hemostatic competence was assessed with thromboelastometry. The effect of fibrinogen supplementation was assessed in a subgroup of coagulopathic patients. Results: Low admission fibrinogen level was independently associated with injury severity score (P < 0.01), shock (P < 0.001), and prehospital fluid volume (P < 0.001). Fibrinogen supplementation during transfusion maintained but did not augment fibrinogen levels. Administration of cryoprecipitate was associated with improved survival. ROTEM parameters correlated with fibrinogen level, and ex vivo fibrinogen administration reversed coagulopathic ROTEM parameters. Fibrinogen level was an independent predictor of mortality at 24 h and 28 days (P < 0.001). Conclusions: Fibrinogen level is decreased in injured patients on admission and is associated with poor outcomes. ROTEM is a rapid means of assessing hypofibrinogenemia. Earlier administration of specific fibrinogen replacement may improve outcomes, and prospective controlled trials are urgently needed.

Objective: To identify an appropriate diagnostic tool for the early diagnosis of acute traumatic coagulopathy and validate this modality through prediction of transfusion requirements in trauma hemorrhage. Design: Prospective observational cohort study. Setting: Level 1 trauma center. Patients: Adult trauma patients who met the local criteria for full trauma team activation. Exclusion criteria included emergency department arrival >2 hrs after injury, >2000 mL of intravenous fluid before emergency department arrival, or transfer from another hospital. Interventions: None. Measurements: Blood was collected on arrival in the emergency department and analyzed with laboratory prothrombin time, point-of-care prothrombin time, and rotational thromboelastometry. Prothrombin time ratio was calculated and acute traumatic coagulopathy defined as laboratory prothrombin time ratio >1.2. Transfusion requirements were recorded for the first 12 hrs following admission. Main Results: Three hundred patients were included in the study. Laboratory prothrombin time results were available at a median of 78 (62–103) mins. Point-of-care prothrombin time ratio had reduced agreement with laboratory prothrombin time ratio in patients with acute traumatic coagulopathy, with 29% false-negative results. In acute traumatic coagulopathy, the rotational thromboelastometry clot amplitude at 5 mins was diminished by 42%, and this persisted throughout clot maturation. Rotational thromboelastometry clotting time was not significantly prolonged. Clot amplitude at a 5-min threshold of ≤35 mm had a detection rate of 77% for acute traumatic coagulopathy with a false-positive rate of 13%. Patients with clot amplitude at 5 mins ≤35 mm were more likely to receive red cell (46% vs. 17%, p < .001) and plasma (37% vs. 11%, p < .001) transfusions. The clot amplitude at 5 mins could identify patients who would require massive transfusion (detection rate of 71%, vs. 43% for prothrombin time ratio >1.2, p < .001). Conclusions: In trauma hemorrhage, prothrombin time ratio is not rapidly available from the laboratory and point-of-care devices can be inaccurate. Acute traumatic coagulopathy is functionally characterized by a reduction in clot strength. With a threshold of clot amplitude at 5 mins of ≤35 mm, rotational thromboelastometry can identify acute traumatic coagulopathy at 5 mins and predict the need for massive transfusion.

Acute coagulopathy of trauma has only been described relatively recently. Developing early in the postinjury phase, it is associated with increased transfusion requirements and poor outcomes. This review examines the possible initiators, mechanism and clinical importance of acute coagulopathy. Acute coagulopathy of trauma occurs in patients with shock and is characterized by a systemic anticoagulation and hyperfibrinolysis. Dilution, acidemia and consumption of coagulation proteases do not appear to be significant factors at this stage. There is evidence to implicate activation of the protein C pathway in this process. Diagnosis of acute coagulopathy currently relies on laboratory assessment of clotting times. These tests do not fully characterize the coagulopathy and have significant limitations, which reduce their clinical utility. Acute coagulopathy results in increased transfusion requirements, incidence of organ dysfunction, critical care stay and mortality. Recognition of an early coagulopathic state has implications for the care of shocked patients and the management of massive transfusion. Identification of novel mechanisms for traumatic coagulopathy may lead to new avenues for drug discovery and therapeutic intervention.