Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis.

INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages. METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality. RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests. CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups. LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.

PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy.

BACKGROUND: The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. METHODS: A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes 'alive and free from massive transfusion' (at least 10 units of RBCs in 24 h) and early 'normalization of coagulopathy' (defined as an international normalized ratio of 1·2 or less). RESULTS: A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. CONCLUSION: A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products.

Non-operative management and immune function after splenic injury.

BACKGROUND: There is still considerable controversy about the importance and method of preserving splenic function after trauma. Recognition of the immune function of the spleen and the risk of overwhelming postsplenectomy infection led to the development of spleen-preserving surgery and non-operative management. More recently angiographic embolization has been used to try to reduce failure of conservative management and preserve splenic function. METHODS: A literature review was performed of the changing treatment of splenic injury over the last century, focusing on whether and how to maintain splenic immune function. RESULTS: Non-operative management continues to be reported as a successful approach in haemodynamically stable patients without other indications for laparotomy, achieving high success rates in both children and adults. Except for haemodynamic instability, reported predictors of failure of conservative treatment should not be seen as absolute contraindications to this approach. Angiographic embolization is generally reported to increase success rates of non-operative management, currently approaching 95 per cent. However, the optimal use of angioembolization is still debated. Splenic immunocompetence after angioembolization remains questionable, although existing studies seem to indicate preserved splenic function. CONCLUSION: Non-operative management has become the treatment of choice to preserve splenic immune function. Current knowledge suggests that immunization is unnecessary after angiographic embolization for splenic injury. Identifying a diagnostic test of splenic function will be important for future studies. Most importantly, in efforts to preserve splenic function, care must be taken not to jeopardize patients at risk of bleeding who require early surgery and splenectomy.

Contrast-enhanced ultrasound of the injured spleen after embolization--comparison with computed tomography.

PURPOSE: The aim of this study was to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) to computed tomography (CT) in trauma patients after splenic embolization. MATERIALS AND METHODS: 22 patients (17 male and 5 female) with a mean age of 32 (15 - 57 years) were studied with ultrasound (US), CEUS and CT in 23 early follow-up examinations 5 days (range: 0 - 12 days) after intervention and 17 late follow-up examinations 69 days (range: 52 - 189 days) after intervention. Perisplenic fluid, hematoma, laceration, infarction, scars and injury grade were evaluated. US and CEUS readings were performed independently by two radiologist, blinded to the CT results. RESULTS: The sensitivity and specificity for CEUS at early follow-up were 85 % and 70 % for perisplenic fluid, 80 % and 94 % for subcapsular hematomas, 83 % and 73 % or lacerations and 75 % and 87 % for infarctions, respectively. The sensitivity and specificity at late follow-up were 60 % and 100 % for subcapsular hematomas, 91 % and 67 % for intrasplenic hematomas, 100 % and 93 % for lacerations and 89 % and 100 % for scars, respectively. The overall sensitivity and specificity for all lesions were 87 % and 88 % at early follow-up (n = 138) and 85 % and 95 % at late follow-up (n = 102), respectively. Compared to CT, CEUS underestimated the injury grade in 2 / 40 cases and overestimated the injury grade in 3/40 cases. CONCLUSION: CEUS is a useful tool for the detection of post-traumatic lesions. It is comparable to CT in follow-up after splenic embolization and may replace CT in follow-up studies.

Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations.

BACKGROUND: Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure. OBJECTIVES: The purpose of the present study was to develop a clinically relevant definition of ATC and understand the etiology of this endogenous coagulopathy. PATIENTS/METHODS: We conducted a retrospective cohort study of trauma patients admitted to five international trauma centers and corroborated our findings in a novel rat model of ATC. Coagulation status on emergency department arrival was correlated with trauma and shock severity, mortality and transfusion requirements. 3646 complete records were available for analysis. RESULTS: Patients arriving with a prothrombin time ratio (PTr) > 1.2 had significantly higher mortality and transfusion requirements than patients with a normal PTr (mortality: 22.7% vs. 7.0%; P < 0.001. Packed red blood cells: 3.5 vs. 1.2 units; P < 0.001. Fresh frozen plasma: 2.1 vs. 0.8 units; P < 0.001). The severity of ATC correlated strongly with the combined degree of injury and shock. The rat model controlled for exogenously induced coagulopathy and mirrored the clinical findings. Significant coagulopathy developed only in animals subjected to both trauma and hemorrhagic shock (PTr: 1.30. APTTr: 1.36; both P < 0.001 compared with sham controls). CONCLUSIONS: ATC develops endogenously in response to a combination of tissue damage and shock. It is associated with increased mortality and transfusion requirements in a dose-dependent manner. When defined by standard clotting times, a PTr > 1.2 should be adopted as a clinically relevant definition of ATC.