BACKGROUND: Traumatic brain injury (TBI) patients present on a spectrum from hypocoagulability to hypercoagulability, depending on the injury complexity, severity, and time since injury. Prior studies have found a unique coagulopathy associated with TBI using conventional coagulation assays such as INR; however, few studies have assessed the association of TBI and coagulopathy using viscoelastic assays that comprehensively evaluate the coagulation in whole blood. This study aims to reevaluate the TBI-specific trauma- induced coagulopathy using arrival thrombelastography. Because brain tissue is high in key procoagulant molecules, we hypothesize that isolated TBI is associated with procoagulant and hypofibrinolytic profiles compared with injuries of the torso, extremities, and polytrauma, including TBI. METHODS: Data are from the prospective Trauma Activation Protocol study. Activated clotting time (ACT), angle, maximum amplitude (MA), 30-minute percent lysis after MA (LY30), and functional fibrinogen levels (FFLEV) were recorded. Patients were categorized into isolated severe TBI (I-TBI), severe TBI with torso and extremity injuries (TBI + TORSO/EXTREMITIES), and isolated torso and extremity injuries (I-TORSO/EXTREMITIES). Poisson regression was used to adjust for multiple confounders. RESULTS: Overall, 572 patients (48 I-TBI, 45 TBI + TORSO/EXTREMITIES, 479 1-TORSO/EXTREMITIES) were included in this analysis. The groups differed in INR, ACT, angle, MA, and FFLEV but not in 30-minute percent lysis. When compared with I-Torso/Extremities, after adjustment for confounders, severe I-TBI was independently associated with ACT less than 128 seconds (relative risk [RR], 1.5; 95% confidence interval [CI], 1.1–2.2), angle less than 65 degrees (RR, 2.2; 95% CI, 1.4–3.6), FFLEV less than 356 (RR, 1.7; 95% CI, 1.2–2.4) but not MA less than 55 mm, hyperfibrinolysis, fibrinolysis shutdown, or partial thromboplastin time (PTT) greater than 30. CONCLUSION: Severe I-TBI was independently associated with a distinct coagulopathy with delayed clot formation but did not appear to be associated with fibrinolysis abnormalities. Low fibrinogen and longer ACT values associated with I-TBI suggest that early coagulation factor replacement may be indicated in I-TBI patients over empiric antifibrinolytic therapy. Mechanisms triggering coagulopathy in TBI are unique and warrant further investigation.

Background-Sex dimorphisms in coagulation have been recognized but whole blood assessment of these dimorphisms and their relationship to outcomes in trauma have not been investigated. This study characterizes the viscoelastic hemostatic profile of severely injured patients by sex and examines how sex-specific coagulation differences affect clinical outcomes, specifically massive transfusion (MT) and death. We hypothesize that severely injured females are more hypercoagulable and thus, have lower rates of MT and mortality.Study Design-Hemostatic profiles and clinical outcomes from all trauma activation patients from two Level I trauma centers were examined with sex as an experimental variable. As part of a prospective study, whole blood was collected and thrombelastography (TEG) was performed. Coagulation profiles were compared between sexes and association with MT and mortality were examined. Poisson regression with robust standard errors was performed.Results-Overall, 464 patients (23% female) were included. By TEG, females had a more hypercoagulable profile, with a higher angle (clot propagation) and maximum amplitude (MA, clot strength). Females were less likely to present with hyperfibrinolysis or prolonged activating clotting time than males. In the setting of depressed clot strength (abnormal MA), female sex

Background: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. Methods: The analysis included 1546 participants (!40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. Results: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96e0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92e0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00e1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01e1.05). Conclusions: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

BACKGROUND Females are hypercoagulable and have survival benefit in trauma-induced coagulopathy (TIC). The mechanism for this sex-specific hypercoagulability is unknown. Platelets and platelet function are central in providing hemostatic potential and are the largest contributor to clot strength. Ligands (adenosine diphosphate [ADP] and platelet-activating factor [PAF]) bind distinct platelet receptors to potentiate activation and aggregation. We hypothesize that female platelets have a differential response to ADP and PAF, resulting in greater aggregation and activation compared to males, and that estradiol pretreatment of male or female platelets enhances this activity. METHODS Platelets were collected from healthy volunteers: premenopausal/postmenopausal females (≤54 years, >54 years) and similarly aged males. Platelet aggregometry and flow cytometry (fibrinogen binding capacity) were examined. After treatment with ADP or PAF, platelet aggregation was assessed with Chronolog and activation assessed by CD41 receptor surface expression using flow cytometry. Aggregation and activation were again assessed after platelet pretreatment with estradiol. RESULTS Healthy volunteers included 12 premenopausal and 13 postmenopausal females and 18 similarly aged males. Female platelets (combined premenopausal and postmenopausal) had increased aggregation with ADP stimulation, as compared to male platelets. Male and female platelets had differential fibrinogen receptor expression, with female platelets (combined premenopausal and postmenopausal) demonstrating robust activation with ADP versus male platelets with PAF. In the presence of estradiol incubation, male platelets' activation with PAF approximated that of females (combined premenopausal and postmenopausal) and activation with PAF was enhanced in both male and female platelets. CONCLUSION Male and female platelets have differential response to stimuli, suggesting sex-dependent signaling and cellular activation. Female platelets have both increased aggregation and activation potential, and estradiol pretreatment feminizes male platelets to approximate female platelet activation with PAF. These findings offer potential explanation for sex-based differences in hemostatic potential in TIC and question whether donor sex of transfused platelets should be considered in resuscitation. Estradiol may also serve as a novel therapeutic adjunct in TIC.

Background: The 6-min walk test (6MWT) is a common means of functional assessment. Its relationship to disability-free survival (DFS) is uncertain. Methods: This sub-study of the Measurement of Exercise Tolerance for Surgery study had co-primary outcome measures: correlation of the preoperative 6MWT distance with 30 day quality of recovery (15-item quality of recovery) and 12 month WHO Disability Assessment Schedule scores. The prognostic utility of the 6MWT and other risk assessment tools for 12 month DFS was assessed with logistic regression and receiver-operating-characteristic-curve analysis. Results: Of 574 patients recruited, 567 (99%) completed the 6MWT. Twelve months after surgery, 16 (2.9%) patients had died and 444 (77%) had DFS. The 6MWT correlated weakly with 30 day 15-item quality of recovery (r¼0.14; P¼0.001) and 12 month WHO Disability Assessment Schedule (r¼e0.23; P<0.0005) scores. When the cohort was split into 6MWT distance tertiles, the adjusted odds ratio of low vs high tertiles for DFS was 3.13 [95% confidence interval (CI): 1.54e6.35]. The only independent variable predictive of DFS was the Duke Activity Status Index (DASI) score (adjusted odds ratio: 1.06; P<0.0005). The area under the receiver-operating-characteristic curve for DFS was 0.63 (95% CI: 0.57e0.70) for the 6MWT, 0.60 (95% CI: 0.53e0.67) for cardiopulmonary-exercise-testing-derived peak oxygen consumption, and 0.70 (95% CI: 0.64e0.76) for the DASI score. Conclusions: Of the risk assessment tools analysed, the DASI was the most predictive of DFS. The 6MWT was safe and comparable with cardiopulmonary exercise testing for all predictive assessments. Future research should aim to determine the optimal 6MWT distance thresholds for risk prediction.

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Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) was first described in the 1950s, but early attempts at REBOA faced several technical challenges. Subsequent advances in endovascular technologies led to renewed interest in employing REBOA for management of *

This paper discusses the pathophysiology of coagulopathy and fibrinolysis secondary to sepsis, the diagnostic tools available to identify the abnormalities, and the available treatments.