Joanna Manson

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.

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.

Circulating Histones Are Mediators of Trauma-associated Lung Injury

RATIONALE Acute lung injury is a common complication after severe trauma, which predisposes patients to multiple organ failure. This syndrome largely accounts for the late mortality that arises and despite many theories, the pathological mechanism is not fully understood. Discovery of histone-induced toxicity in mice presents a new dimension for elucidating the underlying pathophysiology. OBJECTIVES To investigate the pathological roles of circulating histones in trauma-induced lung injury. METHODS Circulating histone levels in patients with severe trauma were determined and correlated with respiratory failure and Sequential Organ Failure Assessment (SOFA) scores. Their cause-effect relationship was studied using cells and mouse models. MEASUREMENTS AND MAIN RESULTS In a cohort of 52 patients with severe nonthoracic blunt trauma, circulating histones surged immediately after trauma to levels that were toxic to cultured endothelial cells. The high levels were significantly associated with the incidence of acute lung injury and SOFA scores, as well as markers of endothelial damage and coagulation activation. In in vitro systems, histones damaged endothelial cells, stimulated cytokine release, and induced neutrophil extracellular trap formation and myeloperoxidase release. Cellular toxicity resulted from their direct membrane interaction and resultant calcium influx. In mouse models, cytokines and markers for endothelial damage and coagulation activation significantly increased immediately after trauma or histone infusion. Pathological examinations showed that lungs were the predominantly affected organ with edema, hemorrhage, microvascular thrombosis, and neutrophil congestion. An anti-histone antibody could reduce these changes and protect mice from histone-induced lethality. CONCLUSIONS This study elucidates a new mechanism for acute lung injury after severe trauma and proposes that circulating histones are viable therapeutic targets for improving survival outcomes in patients.

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.

Trauma alarmins as activators of damage-induced inflammation.

A systemic inflammatory response syndrome (SIRS) is frequently observed after traumatic injury. The response is sterile and the activating stimulus is tissue damage. Endogenous molecules, called alarmins, are reputed to be released by injured tissues but the precise identity of these mediators is unclear. This review summarizes current preclinical and clinical evidence for trauma alarmins and their role in innate immune activation.

Clinical and biomarker profile of trauma-induced secondary cardiac injury

Secondary cardiac injury has been demonstrated in critical illness and is associated with worse outcomes. The aim of this study was to establish the existence of trauma‐induced secondary cardiac injury, and investigate its impact on outcomes in injured patients.

Trauma-induced secondary cardiac injury is associated with hyperacute elevations in inflammatory cytokines.

Introduction Clinical evidence supports the existence of a trauma-induced secondary cardiac injury. Experimental research suggests inflammation as a possible mechanism. The study aimed to determine if there was an early association between inflammation and secondary cardiac injury in trauma patients. Methods A cohort study of critically injured patients between January 2008 and January 2010 was undertaken. Levels of the cardiac biomarkers troponin I and heart-specific fatty acid–binding protein and the cytokines tumor necrosis factor &agr; (TNF-&agr;), interleukin (IL)-6, IL-1&bgr;, and IL-8 were measured on admission to hospital, and again at 24 and 72 h. Participants were reviewed for adverse cardiac events (ACEs) and in-hospital mortality. Results Of 135 patients recruited, 18 (13%) had an ACE. Patients with ACEs had higher admission plasma levels of TNF-&agr; (5.4 vs. 3.8 pg/mL; P = 0.03), IL-6 (140 vs. 58.9 pg/mL, P = 0.009), and IL-8 (19.3 vs. 9.1 pg/mL, P = 0.03) compared with those without events. Hour 24 cytokines were not associated with events, but IL-8 (14.5 vs. 5.8 pg/mL; P = 0.01) and IL-1&bgr; (0.55 vs. 0.19 pg/mL; P = 0.04) were higher in patients with ACEs at 72 hours. Admission IL-6 was independently associated with heart-specific fatty acid–binding protein increase (P < 0.05). Patients who presented with an elevated troponin I combined with either an elevated TNF-&agr; (relative risk [RR], 11.0; 95% confidence interval [CI], 1.8–66.9; P = 0.015), elevated IL-6 (RR, 17.3; 95% CI, 2.9–101.4; P = 0.001), or elevated IL-8 (RR, 15.0; 95% CI, 3.1–72.9; P = 0.008) were at the highest risk of in-hospital death when compared with individuals with normal biomarker and cytokine values. Conclusions There is an association between hyperacute elevations in inflammatory cytokines with cardiac injury and ACEs in critically injured patients. Biomarker evidence of cardiac injury and inflammation on admission is associated with a higher risk of in-hospital death.

Gastroschisis: A multi-centre comparison of management and outcome

BACKGROUND Anecdotal evidence and a handful of literature reports suggest that the outcome for infants born with gastroschisis in many African countries is poor when compared to Western nations. We wished to evaluate current management strategies and outcomes in African and Western units that treat infants with gastroschisis. PATIENTS AND METHODS We conducted a retrospective review of case-notes for infants with gastroschisis who presented to a hospital between 1 January 2004 and 31 December 2007. There were five participating centres, divided for analysis into an African cohort (three centres) and a Western cohort (two centres). RESULTS Fewer infants presented to a hospital with gastroschisis in the African cohort when compared to the Western cohort, particularly when the size of catchment area of each hospital was taken into account. The physiological state of the infant on presentation and management strategy varied widely between centres. Primary closure, preformed silo and surgical silo with delayed closure were all utilised in the African cohort. Use of the preformed silo and delayed abdominal wall closure was the strategy of choice in the Western cohort. The 30-day mortality was 23% and 1% respectively. This primary outcome measure varied considerably in the African cohort but was the same in the two Western units. CONCLUSIONS Gastroschisis in the African cohort was characterised by fewer infants presenting to a hospital and a more variable outcome when compared to the Western cohort. A detailed epidemiological study to determine the incidence of gastroschisis in African countries may provide valuable information. In addition, interventions such as prompt resuscitation, safe neonatal transfer, the use of the preformed silo and parenteral nutrition could improve outcomes in infants with gastroschisis.

Coagulation system changes associated with susceptibility to infection in trauma patients.

BACKGROUND Infection following trauma is associated with increased morbidity and mortality and is common following severe hemorrhage. There is a strong interaction between the coagulation and immunity. The objective of this study was to establish if there was an association between changes in coagulation status after hemorrhage and the subsequent incidence of infection. METHODS Prospective cohort study of adult injured patients presenting to a major trauma center during a 2-year period. Blood was drawn at 24 hours following admission and analyzed using functional thromboelastography testing and laboratory defined tests of coagulation and blood count. Patients were followed up for infectious episodes while in the hospital using Center for Disease Control definitions. RESULTS A total of 158 patients were recruited; 71 (45%) developed infection and were older (44 years vs. 32 years, p = 0.01) and more severely injured (Injury Severity Score [ISS], 25 vs.10; p < 0.01). White blood cell counts at 24 hours were normal, and there was no difference between groups (both 9.6 × 109/L). Protein C was lower in those with infection (70.2 IU/dL vs. 83.3 IU/dL, p = 0.02), with a dose-dependent increase in infection as levels of protein C decreased. Plasmin activation at 24 hours was also strongly associated with infection plasmin-antiplasmin (infection vs. no infection, 6,156 &mgr;g/L vs. 3,324 &mgr;g/L, p = 0.03). The infection cohort had overall 12% lower procoagulant levels (varied between factor VIII 6.4% and factor II 16.2%). CONCLUSION There is a strong association between the status of the coagulation system after 24 hours and the development of infection following trauma. Improved early coagulation management may decrease infection rates in this patient group. LEVEL OF EVIDENCE Prognostic prospective study, level III.

Major trauma and urban cyclists: physiological status and injury profile

Introduction Pedal cycling in cities has the potential to deliver significant health and economic benefits for individuals and society. Safety is the main concern for potential cyclists although the statistical risk of death is low. Little is known about the severity of injuries sustained by city cyclists and their outcome. Aim The aim of this study was to characterise the physiological status and injury profile of cyclists admitted to our urban major trauma centre (MTC). Methods Database analysis of cyclist casualties between 2004 and 2009. The physiological parameters examined were admission systolic blood pressure (SBP), admission base deficit and prehospital Glasgow Coma Scale. Results 265 cyclists required full trauma-team activation. 82% were injured during a collision with a motorised vehicle. The majority (73%) had collided with a car or a heavy goods vehicle (HGV). These casualties formed the cohort for further analysis. Cyclists who collided with an HGV were more severely injured and had a higher mortality rate. Low SBP and high base deficit indicate that haemorrhagic shock is a key feature of HGV casualties. Conclusion Collision with any vehicle can result in death or serious injury to a cyclist. Injury patterns vary with the type of vehicle involved. HGVs were associated with severe injuries and death as a result of uncontrollable haemorrhage. Awareness of this injury profile may aid prehospital management and expedite transfer to MTC care. Rapid haemorrhage control may salvage some, but not all, of these casualties. The need for continued collision prevention strategies and long-term outcome data collection in trauma patients is highlighted.