Ross Davenport

Acute coagulopathy of trauma: mechanism, identification and effect.

Purpose of reviewAcute 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. Recent findingsAcute 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. SummaryAcute 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.

Functional definition and characterization of acute traumatic coagulopathy.

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.

Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes

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.

The incidence and magnitude of fibrinolytic activation in trauma patients

Summary.  Background: Trauma is a global disease, with over 2.5 million deaths annually from hemorrhage and coagulopathy. Overt hyperfibrinolysis is rare in trauma, and is associated with massive fatal injuries. Paradoxically, clinical trials suggest a much broader indication for antifibrinolytics.

Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2.

BACKGROUND Damage control resuscitation targets acute traumatic coagulopathy with the early administration of high-dose fresh frozen plasma (FFP). FFP is administered empirically and as a ratio with the number of packed red blood cells (PRBC). There is controversy over the optimal FFP:PRBC ratio with respect to outcomes, and their hemostatic effects have not been studied. We report preliminary findings on the effects of different FFP:PRBC ratios on coagulation. METHODS This is a prospective observational cohort study of trauma patients requiring >4 U of PRBCs. Blood was drawn before and after each 4-U PRBC interval for prothrombin time and analysis by rotational thromboelastometry. Interval change in coagulation parameters were compared with the FFP:PRBC ratio received during each interval. RESULTS Sixty 4-U PRBC intervals from 50 patients were available for analysis. All measures of coagulation deteriorated with low FFP:PRBC ratios (<1:2). Maximal hemostatic effect was observed in the 1:2 to 3:4 group: 12% decrease in prothrombin time (p=0.006), 56% decrease in clotting time (p=0.047), and 38% increase in maximum clot firmness (p=0.024). Transfusion with ≥1:1 ratio did not confer any additional improvement. There was a marked variability in response to FFP, and hemostatic function deteriorated in some patients exposed to 1:1 ratios. The beneficial effects of plasma were confined to patients with coagulopathy. CONCLUSIONS Interim results from this prospective study suggest that FFP:PRBC ratios of ≥1:1 do not confer any additional advantage over ratios of 1:2 to 3:4. Hemostatic benefits of plasma therapy are limited to patients with coagulopathy.

Acute traumatic coagulopathy.

Purpose of review Recent therapeutic and observational studies have demonstrated improved survival with better management of haemostasis early after injury. This review delineates our current understanding of the clinical importance, aetiology and pathophysiology of acute traumatic coagulopathy (ATC). Recent findings Trauma causes an acute disruption of the equilibrium between all components of haemostasis (coagulation, anticoagulation, fibrinolysis, platelets and endothelium). In patients with a combination of severe tissue damage and systemic hypoperfusion, this will progress rapidly to an endogenous coagulopathy that is independently associated with worse outcomes. New discoveries of the interactions between neurohormonal, vascular, and coagulation systems are beginning to explain how this haemostatic impairment develops and offer novel targets for therapeutic manipulation. Routine coagulation screening tests are ineffective for diagnosing ATC and guiding resuscitation in real-time. Viscoelastic coagulation tests (such as ROTEM or TEG) have emerged as practical, rapid and sensitive diagnostic modalities. Their role in therapeutic targeting requires further validation. Summary Conventional concepts of traumatic coagulopathy as a late occurring condition in response to iatrogenic haemodilution are redundant. ATC is an endogenous impairment of haemostasis that begins at the moment of injury. Further outcome improvements are possible with better understanding of the process by which this coagulopathy develops and how it may be inhibited.

Pathogenesis of acute traumatic coagulopathy.

Acute traumatic coagulopathy (ATC) is an early endogenous process, driven by the combination of tissue injury and shock that is associated with increased mortality and worse outcomes in the polytrauma patient. This review summarizes our current understanding of the pathophysiology of ATC and the role of rapid diagnostics in the management of severe trauma hemorrhage. In particular we consider diagnostic and therapeutic strategies for bleeding trauma patients with short versus long prehospital times and the concept of remote damage control resuscitation. Endothelial activation of Protein C is a central mechanism of ATC, which produces rapid anticoagulation and fibrinolysis following severe trauma. Continued blood loss, hypothermia, acidosis, and hemodilution potentiate ATC and lead to a global derangement in all components of hemostasis. The contribution and interplay between platelet activity, fibrinogen utilization, endothelial dysfunction, and neurohormonal pathways remain to be defined in ATC pathogenesis but may offer novel therapeutic targets. Conventional laboratory‐based tests of coagulation have a limited role in the early management of major trauma hemorrhage. TEG and ROTEM provide a rapid evaluation of clot dynamics in whole blood and are of greater value than coagulation screens in diagnosing and managing trauma hemorrhage.

Hemostatic resuscitation is neither hemostatic nor resuscitative in trauma hemorrhage.

BACKGROUND Trauma hemorrhage continues to carry a high mortality rate despite changes in modern practice. Traditional approaches to the massively bleeding patient have been shown to result in persistent coagulopathy, bleeding, and poor outcomes. Hemostatic (or damage control) resuscitation developed from the discovery of acute traumatic coagulopathy and increased recognition of the negative consequences of dilutional coagulopathy. These strategies concentrate on early delivery of coagulation therapy combined with permissive hypotension. The efficacy of hemostatic resuscitation in correcting coagulopathy and restoring tissue perfusion during acute hemorrhage has not been studied. METHODS This is a prospective cohort study of ROTEM and lactate measurements taken from trauma patients recruited to the multicenter Activation of Coagulation and Inflammation in Trauma (ACIT) study. A blood sample is taken on arrival and during the acute bleeding phase after administration of every 4 U of packed red blood cells (PRBCs), up to 12 U. The quantity of blood products administered within each interval is recorded. RESULTS Of the 106 study patients receiving at least 4 U of PRBC, 27 received 8 U to 11 U of PRBC and 31 received more than 12 U of PRBC. Average admission lactate was 6.2 mEq/L. Patients with high lactate (≥5 mEq/L) on admission did not clear lactate until hemorrhage control was achieved, and no further PRBC units were required. On admission, 43% of the patients were coagulopathic (clot amplitude at 5 minutes ⩽ 35 mm). This increased to 49% by PRBC 4; 62% by PRBC 8 and 68% at PRBC 12. The average fresh frozen plasma/PRBC ratio between intervals was 0.5 for 0 U to 4 U of PRBC, 0.9 for 5 U to 8 U of PRBC, 0.7 for 9 U to 12 U of PRBC. There was no improvement in any ROTEM parameter during ongoing bleeding. CONCLUSION While hemostatic resuscitation offers several advantages over historical strategies, it still does not achieve correction of hypoperfusion or coagulopathy during the acute phase of trauma hemorrhage. Significant opportunities still exist to improve management and improve outcomes for bleeding trauma patients. LEVEL OF EVIDENCE Epidemiologic study, level III.

A major trauma centre is a specialty hospital not a hospital of specialties

High estimates of preventable death rates have renewed the impetus for national regionalization of trauma care. Institution of a specialist multidisciplinary trauma service and performance improvement programme was hypothesized to have resulted in improved outcomes for severely injured patients.

Management of major trauma haemorrhage: treatment priorities and controversies.

The severely injured trauma patient often arrives in the emergency department bleeding, coagulopathic and in need of a blood transfusion. The diagnosis and management of these patients has vastly improved with a better understanding of acute traumatic coagulopathy (ATC). In the emergency setting, traditional laboratory coagulation screens are of limited use in the diagnosis and management of life‐threatening bleeding. Whole blood assays, such as thrombelastography (TEG) and rotational thrombelastometry (ROTEM) provide a rapid evaluation of clot formation, strength and lysis. Rapid diagnosis of ATC and aggressive haemostatic transfusion strategies utilizing early high doses of plasma are associated with improved outcomes in trauma. At present there is no accurate guide for transfusion in trauma, therefore blood and clotting products are administered on an empiric basis. Targeted transfusion therapy for major trauma haemorrhage based on comprehensive and rapid measures of coagulation e.g. TEG/ROTEM may lead to improved outcomes while optimizing blood utilization. Evidence for the clinical application of TEG and ROTEM in trauma is emerging with a number of studies evaluating their ability to diagnose coagulopathy early and facilitate goal‐directed transfusion. This review explores current controversies and best practice in the diagnosis and management of major haemorrhage in trauma.