Sex dimorphisms in coagulation: Implications in trauma-induced coagulopathy and trauma resuscitation.

Trauma-induced coagulopathy (TIC) is one of the leading causes of preventable death in injured patients. Consequently, it is imperative to understand the mechanisms underlying TIC and how to mitigate this mortality. An opportunity for advancement stems from the awareness that coagulation demonstrates a strong sex-dependent effect. Females exhibit a relative hypercoagulability compared to males, which persists after injury and confers improved outcomes. The mechanisms underlying sex dimorphisms in coagulation and its protective effect after injury have yet to be elucidated. This review explores sex dimorphisms in enzymatic hemostasis, fibrinogen, platelets, and fibrinolysis, with implications for resuscitation of patients with TIC.

Using Chest X-Ray to Predict Tube Thoracostomy in Traumatic Pneumothorax: A Single-Institution Retrospective Review.

INTRODUCTION: Traumatic pneumothorax (PTX) is a common occurrence in thoracic trauma patients, with a majority requiring tube thoracostomy (TT) for management. Recently, the "35-mm" rule has advocated for observation of patients with PTX less than 35 mm on chest computed tomography (CT) scan. This rule has not been examined in chest x-ray (CXR). We hypothesize that a similar size cutoff can be determined in CXR predictive of need for tube thoracostomy. METHODS: We performed a single-institution retrospective review of patients with traumatic PTX from 2018 - 2022, excluding those who underwent TT prior to CXR. Primary outcomes were size of pneumothorax on CXR and need for TT; secondary outcome was failed observation, defined as TT more than four hours after presentation. To determine the size cutoff on CXR to predict TT need, area under the receiver operating curve (AUROC) analyses were performed and Youden's index calculated (significance at p < 0.05). Predictors of failure were calculated using logistic regression. RESULTS: There were 359 pneumothoraces in 322 patients (94.4% blunt trauma, median injury severity score 14). Of these, 82 (22.8%) had a TT placed within the first four hours. Fifty-five of observed patients (21.2%) failed, and these patients had a larger PTX on CXR (8.6 mm [5.0 - 18.0 mm] versus 0.0 mm [0.0 - 2.3 mm] (p < 0.001)). CXR PTX size correlated moderately with CT size (r = 0.31, p < 0.001) and was highly predictive of need for TT insertion (AUC 0.75, p < 0.0001), with an optimal size cutoff predicting TT need of 38 mm. CONCLUSION: CXR imaging size was predictive of need for TT, with an optimal size cutoff on CXR of 38 mm, approaching the "35-mm rule." In addition to size, failed observation was predicted by presenting lactic acidosis and need for supplemental oxygen. This demonstrates this cutoff should be considered for prospective study in CXR.Level of Evidence: III; Therapeutic/Care Management.

Surgical Apgar scores predict complications after emergency general surgery laparotomy.

BACKGROUND: The Surgical Apgar Score (SAS) is a 10-point validated score comprised of three intraoperative variables (blood loss, lowest heart rate, and lowest mean arterial pressure). Lower scores are worse and predict major postoperative complications. The SAS has not been applied in emergency general surgery (EGS) but may help guide postoperative disposition. We hypothesize that SAS can predict complications in EGS patients undergoing a laparotomy. METHODS: We performed a retrospective review of adult patients at a single, quaternary care center who underwent an exploratory laparotomy for EGS conditions within 6 hours of surgical consultation from 2015 to 2019. Patients were grouped by whether they experienced a postoperative complication (systemic, surgical, and/or death). Multivariable regression was performed to predict complications, accounting for SAS and other statistically significant variables between groups. Using this model, predicted probabilities of a complication were generated for each SAS. RESULTS: The cohort comprised 482 patients: 32.8% (n = 158) experienced a complication, while 67.2% (n = 324) did not. Patients with complications were older, frailer, more often male, had worse SAS (6 vs. 7, p < 0.0001) and American Society of Anesthesiologists scores, and higher rates of perforated hollow viscus ( p = 0.0003) and open abdomens ( p < 0.0001). On multivariable regression, an increasing SAS independently predicted less complications (adjusted odds ratio, 0.85; 95% confidence interval, 0.75-0.96; p = 0.009). An SAS ≤4 was associated with a 49.2% predicted chance of complications, greater rates of septic shock (9.7% vs. 3%, p = 0.01), respiratory failure (20.5% vs. 10.8%, p = 0.02), and death (24.1% vs. 7.5%, p < 0.0001). An SAS ≤ 4 did not correlate with surgical complications ( p = 0.1). CONCLUSION: The SAS accurately predicts postoperative complications in EGS patients undergoing urgent laparotomy, with an SAS ≤ 4 identifying patients at risk for septic shock, respiratory failure, and mortality. This tool can aid in rapidly determining postoperative disposition and resource allocation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

A metabolomic and proteomic analysis of pathologic hypercoagulability in traumatic brain injury patients after dura violation.

BACKGROUND: The coagulopathy of traumatic brain injury (TBI) remains poorly understood. Contradictory descriptions highlight the distinction between systemic and local coagulation, with descriptions of systemic hypercoagulability despite intracranial hypocoagulopathy. This perplexing coagulation profile has been hypothesized to be due to tissue factor release. The objective of this study was to assess the coagulation profile of TBI patients undergoing neurosurgical procedures. We hypothesize that dura violation is associated with higher tissue factor and conversion to a hypercoagulable profile and unique metabolomic and proteomic phenotype. METHODS: This is a prospective, observational cohort study of all adult TBI patients at an urban, Level I trauma center who underwent a neurosurgical procedure from 2019 to 2021. Whole blood samples were collected before and then 1 hour following dura violation. Citrated rapid and tissue plasminogen activator (tPA) thrombelastography (TEG) were performed, in addition to measurement of tissue factory activity, metabolomics, and proteomics. RESULTS: Overall, 57 patients were included. The majority (61%) were male, the median age was 52 years, 70% presented after blunt trauma, and the median Glasgow Coma Score was 7. Compared with pre-dura violation, post-dura violation blood demonstrated systemic hypercoagulability, with a significant increase in clot strength (maximum amplitude of 74.4 mm vs. 63.5 mm; p < 0.0001) and a significant decrease in fibrinolysis (LY30 on tPAchallenged TEG of 1.4% vs. 2.6%; p = 0.04). There were no statistically significant differences in tissue factor. Metabolomics revealed notable increases in metabolites involved in late glycolysis, cysteine, and one-carbon metabolites, and metabolites involved in endothelial dysfunction/arginine metabolism/responses to hypoxia. Proteomics revealed notable increase in proteins related to platelet activation and fibrinolysis inhibition. CONCLUSION: A systemic hypercoagulability is observed in TBI patients, characterized by increased clot strength and decreased fibrinolysis and a unique metabolomic and proteomics phenotype independent of tissue factor levels.

The Trauma Fellow's Perspective on Grit and Resilience and Its Role in Wellness.

Purpose of Review: To describe the unique stressors of surgical training and fellowship and how grit and resilience influence trainee wellness. Recent Findings: Surgical training is an intense, high-stress experience. For fellows-in-training, unique stressors are associated with this chapter of training, from financial pressors to the stress of job acquisition. Wellness is essential for surgical fellows, not just for the critical need for quality mental health of providers, but also for the patients who are also affected by provider burnout. There are various wellness programs that can be instituted nationally and institutionally to optimize fellow wellness, but one of the most high-yield foci for fellow wellness is focused mentorship, the key to assuring wellness and harnessing grit. Summary: Surgical residency and fellowship are prodigiously demanding experiences, which mandate grit and resilience. It is imperative that widespread cultural and institutional changes take place to best support surgical trainees.

Early Surgical Stabilization of Rib Fractures is Feasible in Patients With Non-Urgent Operative Pelvic Injuries.

INTRODUCTION: The feasibility of prioritizing surgical stabilization of rib fractures (SSRF) in patients with other injuries is unknown. The purpose of this study was to evaluate the timing and outcomes of SSRF between patients with and without non-urgent operative pelvic injuries. PATIENTS AND METHODS: In this retrospective observational study, all patients between 2010 and 2020 who underwent SSRF (SSRF group) and those who underwent SSRF and non-urgent operative management of pelvic fractures (SSRF + P group) were included. Demographics, injury characteristics, operative details, and outcomes were compared between the 2 groups. RESULTS: Over 11 years, 154 SSRF patients were identified, with 143 patients in the SSRF group (93%) and 11 patients in the SSRF + P group (7%). Median number of rib fractures (7 vs 9, P = .04), total number of fractures (11 vs 15, P < .01), and flail segment (54% vs 91%, P = .02) were higher in SSRF + P group. Median time to SSRF was similar (0 vs 1 day, P = .20) between the 2 groups. Median time to pelvic fixation was 3 days in SSRF + P group and 8 out of 11 patients (73%) underwent SSRF prior to pelvic fixation. Median operative time (137 vs 178 mins, P = .14) and median number of ribs plated (4 vs 5, P = .05) were higher in SSRF + P group. There was no difference in SSRF-related complications, pelvic fracture-related complications from operative positioning, rates of pneumonia, or mortality between the 2 groups. CONCLUSIONS: SSRF can be performed early in patients with non-urgent operative pelvic injuries without a difference in pelvic fracture-related complications, SSRF-related complications, pneumonia, or mortality.

Elucidating the molecular mechanisms of fibrinolytic shutdown after severe injury: The role of thrombin-activatable fibrinolysis inhibitor.

BACKGROUND: The mechanisms underlying trauma-induced coagulopathy remain elusive. Hyperfibrinolysis has been linked to increased plasminogen activation and antiprotease consumption; however, the mechanistic players in its counterpart, fibrinolysis shutdown, remain unclear. We hypothesize that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a major role in fibrinolytic shutdown after injury. METHODS: As part of this observational cohort study, whole blood was collected from trauma activation patients at a single, level 1 trauma center. Citrated rapid thrombelastography and the following enzyme-linked immunosorbent assays were conducted: thrombin, antithrombin, thrombin-antithrombin complex, TAFI, plasminogen, antiplasmin, plasmin-antiplasmin (PAP), tissue plasminogen activator, plasminogen activator inhibitor 1, and tissue plasminogen activator-plasminogen activator inhibitor 1 complex. Univariate and cluster analysis were performed. RESULTS: Overall, 56 patients (median age, 33.5 years; 70% male) were included. The majority (57%) presented after blunt mechanism and with severe injury (median New Injury Severity Score, 27). Two clusters of patients were identified: Group 1 (normal fibrinolysis, n = 21) and Group 2 (fibrinolysis shutdown, n = 35). Group 2 had significantly lower fibrinolysis with a median LY30 of 1.1% (interquartile range [IQR], 0.1-1.9%) versus 2.1% (IQR, 0.5-2.8%) in Group 1; while the median LY30 was within physiologic range, 45% of patients in Group 2 were in shutdown (vs. 24% in Group 1, p = 0.09). Compared with Group 1, Group 2 had significantly higher PAP (median, 4.7 [IQR, 1.7-9.3] vs. 1.4 [1.0-2.1] µg/mL in Group 1; p = 0.002) and higher TAFI (median, 152.5% [IQR, 110.3-190.7%] vs. 121.9% [IQR, 93.2-155.6%]; p = 0.04). There was a strong correlation between PAP and TAFI ( R2 = 0.5, p = 0.0002). CONCLUSION: The presented data characterize fibrinolytic shutdown, indicating an initial plasmin burst followed by diminished fibrinolysis, which is distinct from hypofibrinolysis (inadequate plasmin burst and fibrinolysis). After an initial thrombin and plasmin burst (increased PAP), fibrinolysis is inhibited, mediated in part by increased TAFI.

Estradiol provokes hypercoagulability and affects fibrin biology: A mechanistic exploration of sex dimorphisms in coagulation.

BACKGROUND: Sex dimorphisms in coagulation are well established, with female-specific hypercoagulability conferring a survival benefit in the setting of trauma-induced coagulopathy (TIC). The mechanism behind these phenomena remains to be elucidated. We hypothesize that estradiol provokes a hypercoagulable profile and alters clot proteomics and fibrin crosslinking. METHODS: Whole blood was collected from healthy adult volunteers (n = 30). A battery of thrombelastography (TEG) assays (native, kaolin, platelet-mapping, functional fibrinogen), whole blood thrombin generation, proteomics, and clot structure architecture (via analysis of fibrin crosslinks and fluorescent fibrinogen-visualized clots) were performed after pre-treatment of the blood with physiologic concentrations of beta-estradiol. In addition, a prospective study of coagulation through the menstrual cycle was conducted by collecting blood from women on peak and nadir estrogen days in the standard 28-day menstrual cycle. RESULTS: On TEG, in females, estradiol provoked a hypercoagulable phenotype, specifically a shorter time to clot formation and greater thrombin generation, greater rate of clot propagation and functional fibrinogen, higher clot strength, and diminished clot fibrinolysis. In both males and females, estradiol increased platelet hyperactivity. Similar changes were seen in time to clot formation and clot strength in vivo during peak estrus of the menstrual cycle. On proteomic analysis, in both males and females, estradiol was associated with increases in abundance of several procoagulant and antifibrinolytic proteins. Crosslinking mass spectrometry analysis showed addition of estradiol increased the abundance of several FXIII crosslinks within the FIBA alpha chain in both sexes. Fluorescent fibrinogen analysis revealed a trend toward increased fiber resolvability index after addition of estradiol. CONCLUSION: Estradiol provokes a hypercoagulable phenotype, affecting time to clot formation, clot propagation, clot strength, clot fibrinolysis, and clot structure. In sum, these data highlight the role of estradiol is driving female-specific hypercoagulability and highlights its potential role as a therapeutic adjunct in resuscitation of TIC.

Beyond uterine atony: characterizing postpartum hemorrhage coagulopathy.

BACKGROUND: Postpartum hemorrhage is a leading cause of morbidity and mortality worldwide, yet the associated early coagulopathy is not well defined. OBJECTIVE: We hypothesized that women who develop postpartum hemorrhage have a distinct derangement of thrombin generation and coagulation factors compared with postpartum women without postpartum hemorrhage. STUDY DESIGN: This prospective study of pregnant patients with postpartum hemorrhage was completed at a single urban hospital. Blood was drawn on postpartum hemorrhage diagnosis and 2 and 4 hours later. Assays of patients with postpartum hemorrhage included thrombelastography, whole blood thrombin generation, coagulation factor activity, tissue factor levels and activity, and tissue factor pathway inhibitor levels, which were compared with that of patients without postpartum hemorrhage. RESULTS: A total of 81 patients were included in this study. Of those patients, 66 had postpartum hemorrhage, and 15 served as controls. Compared with patients without PPH, patients with postpartum hemorrhage had lower fibrinogen levels (469.0 mg/dL vs 411.0 mg/dL; P=.02), increased tissue plasminogen activator resistance (fibrinolysis 30 minutes after maximal clot strength: 8.7% vs 4.2%; P=.02), decreased peak thrombin concentration (150.2 nM vs 40.7 nM; P=.01), and decreased maximal rate of thrombin generation (60.1 nM/minute vs 2.8 nM/minute; P=.02). Furthermore, compared with patients without postpartum hemorrhage, patients with postpartum hemorrhage had decreased tissue factor levels (444.3 pg/mL vs 267.1 pg/mL; P=.02) and increased tissue factor pathway inhibitor levels (0.6 U/mL vs 0.8 U/mL; P=.04), with decreased tissue factor pathway inhibitor ratios (624 vs 299; P=.01). CONCLUSION: PPH is not only an issue of uterine tone and mechanical bleeding but also a distinct coagulopathy that is characterized by decreased fibrinogen level, clot breakdown resistance, and markedly low thrombin generation. This pathology seemed to be driven by low tissue factor and high tissue factor pathway inhibitor levels.

Hemorrhagic shock and tissue injury provoke distinct components of trauma-induced coagulopathy in a swine model.

INTRODUCTION: Tissue injury (TI) and hemorrhagic shock (HS) are the major contributors to trauma-induced coagulopathy (TIC). However, the individual contributions of these insults are difficult to discern clinically because they typically coexist. TI has been reported to release procoagulants, while HS has been associated with bleeding. We developed a large animal model to isolate TI and HS and characterize their individual mechanistic pathways. We hypothesized that while TI and HS are both drivers of TIC, they provoke different pathways; specifically, TI reduces time to clotting, whereas, HS decreases clot strength stimulates hyperfibrinolysis. METHODS: After induction of general anesthesia, 50 kg male, Yorkshire swine underwent isolated TI (bilateral muscle cutdown of quadriceps, bilateral femur fractures) or isolated HS (controlled bleeding to a base excess target of - 5 mmol/l) and observed for 240 min. Thrombelastography (TEG), calcium levels, thrombin activatable fibrinolysis inhibitor (TAFI), protein C, plasminogen activator inhibitor 1 (PAI-1), and plasminogen activator inhibitor 1/tissue-type plasminogen activator complex (PAI-1-tPA) were analyzed at pre-selected timepoints. Linear mixed models for repeated measures were used to compare results throughout the model. RESULTS: TI resulted in elevated histone release which peaked at 120 min (p = 0.02), and this was associated with reduced time to clot formation (R time) by 240 min (p = 0.006). HS decreased clot strength at time 30 min (p = 0.003), with a significant decline in calcium (p = 0.001). At study completion, HS animals had elevated PAI-1 (p = 0.01) and PAI-1-tPA (p = 0.04), showing a trend toward hyperfibrinolysis, while TI animals had suppressed fibrinolysis. Protein C, TAFI and skeletal myosin were not different among the groups. CONCLUSION: Isolated injury in animal models can help elucidate the mechanistic pathways leading to TIC. Our results suggest that isolated TI leads to early histone release and a hypercoagulable state, with suppressed fibrinolysis. In contrast, HS promotes poor clot strength and hyperfibrinolysis resulting in hypocoagulability.

Inflate and pack! Pelvic packing combined with REBOA deployment prevents hemorrhage related deaths in unstable pelvic fractures.

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is advocated for hemorrhage control in pelvic fracture patients in shock. We evaluated REBOA in patients undergoing preperitoneal pelvic packing (PPP) for pelvic fracture-related hemorrhage. METHODS: Retrospective, single-institution study of unstable pelvic fractures (hemodynamic instability despite 2 units of red blood cells (RBCs) and fracture identified on x-ray). Management included the placement of a Zone III REBOA in the emergency department (ED) for systolic blood pressure <80 mmHg. All PPP patients were included and analyzed for injury characteristics, transfusion requirements, outcomes and complications. Additionally, patients who received REBOA (REBOA+) were compared to those that did not (REBOA-). RESULTS: During the study period (January 2015 - January 2019), 652 pelvic fracture patients were admitted; 78 consecutive patients underwent PPP. Median RBCs at PPP completion compared to 24 h post-packing were 11 versus 3 units (p<0.05). Median time to operation was 45 min. After PPP, 7 (9%) patients underwent angioembolization. Mortality was 14%. No mortalities were due to ongoing pelvic fracture hemorrhage or physiologic exhaustion; all were a withdrawal of life sustaining support, most commonly due to neurologic insults (TBI/fat emboli = 6, stroke/spinal cord injury = 3). REBOA+ patients (n = 31) had a significantly higher injury severity score (45 vs 38, p<0.01) and higher heart rate (130 vs 118 beats per minute, p = 0.04) than REBOA-. The systolic blood pressure, base deficit, and number of RBCs transfused in the ED, and time spent in the ED were similar between groups. REBOA+ had a higher median transfusion of RBCs at PPP completion (11 units vs 5 units, p<0.01) but similar RBC transfusion in the 24 h after PPP (2 vs 1 units, p = 0.27). Mortality, pelvic infection, and ICU length of stay was not different between these cohorts. CONCLUSION: PPP with REBOA was utilized in more severely injured patients with greater physiologic derangements. Although REBOA patients required greater transfusion requirements, there were no deaths due to acute pelvic hemorrhage. This suggests the combination of REBOA with PPP provides life-saving hemorrhage control in otherwise devastating injuries.

Hormones, age, and sex affect platelet responsiveness in vitro.

BACKGROUND: Female sex confers a survival advantage following severe injury in the setting of trauma-induced coagulopathy, with female platelets having heightened responsiveness likely due to estrogen. The effects of testosterone on platelet biology are unknown, and platelets express both estradiol and androgen receptors on the plasma membrane. We hypothesize testosterone decreases platelet responses in vitro, and there are baseline differences in platelet function and metabolism stratified by sex/age. STUDY DESIGN AND METHODS: Apheresis platelets were collected from: older males (OM) ≥45 years, younger males (YM) <45 years, older females (OF) ≥54 years, and younger females (YF) <54 years, and testosterone and estradiol were measured. Platelets were incubated with testosterone (5.31 ng/ml), estradiol (105 pg/ml) or vehicle and stimulated with buffer, adenosine diphosphate (20 µM), platelet activating factor (2 µM), or thrombin (0.3 U/ml). Aggregation, CD62P surface expression, fibrinogen receptor surface expression, and platelet mitochondrial metabolism were measured. RESULTS: Testosterone significantly inhibited aggregation in OF and OM (p < .05), inhibited CD41a expression in YF, YM, and OM (p < .05), and affected a few of the baseline amounts of CD62P surface expression but not platelet activation to platelet-activating factor and adenosine diphosphate, and variably changed platelet metabolism. DISCUSSION: Platelets have sex- and age-specific aggregation, receptor expression, and metabolism. Testosterone decreases platelet function dependent on the stimulus, age, and sex. Similarly, platelet metabolism has varying responses to sex hormones with baseline metabolic differences dependent upon sex and age.

Patient characteristics and diagnostic tests associated with syncopal falls: A Southwestern surgical congress multicenter study.

BACKGROUND: Patients suspected of syncope frequently undergo laboratory and imaging studies to determine the etiology of the syncope. Variability exists in these workups across institutions. The purpose of this study was to evaluate the utilization and diagnostic yield of these workups and the patient characteristics associated with syncopal falls. METHODS: A multi-institutional retrospective review was performed on adult patients admitted after a fall between 1/2017-12/2018. Syncopal falls were compared to non-syncopal falls. RESULTS: 4478 patients were included. There were 795 (18%) patients with a syncopal fall. Electrocardiogram, troponin, echocardiogram, CT angiography (CTA), and carotid ultrasound were more frequently tested in syncope patients compared to non-syncope patients. Syncope patients had higher rates of positive telemetry/Holter monitoring, CTAs, and electroencephalograms. CONCLUSION: Patients who sustain syncopal falls frequently undergo diagnostic testing without a higher yield to determine the etiology of syncope.

Developing and leading a sustainable organization for early career acute care surgeons: Lessons from the inaugural American Association for the Surgery of Trauma Associate Member Council.

ABSTRACT: The associate membership of the American Association for the Surgery of Trauma (AAST) was established in 2019 to create a defined but incorporated entity within the larger AAST for the next generation of acute care surgeons. The Associate Member Council (AMC) was subsequently established in 2020 to provide the new AM with an elected group of leaders who would represent them within the AAST. In its inaugural year, this cohort of junior faculty and surgical trainees had developed for the AM a set of bylaws, a mission statement, a strategic vision, and a succession plan. The experience of the AAST AMC is exemplary of what can be accomplished with collaboration, mentorship, innovation, and tenacity. It has the potential to serve as a template for the creation and vitalization of future professional groups. In this piece, the AMC proposes a blueprint for the successful conception of a new organization.

Apolipoprotein A-I, elevated in trauma patients, inhibits platelet activation and decreases clot strength.

Apolipoprotein A-I (ApoA-I) is elevated in the plasma of a subgroup of trauma patients with systemic hyperfibrinolysis. We hypothesize that apoA-I inhibits platelet activation and clot formation. The effects of apoA-I on human platelet activation and clot formation were assessed by whole blood thrombelastography (TEG), platelet aggregometry, P-selectin surface expression, microfluidic adhesion, and Akt phosphorylation. Mouse models of carotid artery thrombosis and pulmonary embolism were used to assess the effects of apoA-I in vivo. The ApoA-1 receptor was investigated with transgenic mice knockouts (KO) for the scavenger receptor class B member 1 (SR-BI). Compared to controls, exogenous human apoA-I inhibited arachidonic acid and collagen-mediated human and mouse platelet aggregation, decreased P-selectin surface expression and Akt activation, resulting in diminished clot strength and increased clot lysis by TEG. ApoA-I also decreased platelet aggregate size formed on a collagen surface under flow. In vivo, apoA-I delayed vessel occlusion in an arterial thrombosis model and conferred a survival advantage in a pulmonary embolism model. SR-BI KO mice significantly reduced apoA-I inhibition of platelet aggregation versus wild-type platelets. Exogenous human apoA-I inhibits platelet activation, decreases clot strength and stability, and protects mice from arterial and venous thrombosis via the SR-BI receptor.