Antithrombin III Levels and Outcomes Among Patients With Trauma.

Importance: Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma. Objective: To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma. Design, Setting, and Participants: This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024. Main Outcomes and Measures: The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality. Results: The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT. Conclusions and Relevance: In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

Digital twin mathematical models suggest individualized hemorrhagic shock resuscitation strategies.

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting. METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation. RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well as the outcome and time of death in the PROMMTT cohort. Model simulation suggests that resuscitation with plasma and red blood cells outperformed resuscitation with crystalloid or plasma alone, and that earlier plasma resuscitation reduced injury severity and increased survival time. CONCLUSIONS: This workflow may serve as a translational bridge from pre-clinical to clinical studies in trauma-associated hemorrhagic shock and other complex disease settings.

Research to improve survival in patients with severe bleeding after major trauma presents many challenges. Here, we created a computer model to simulate the effects of severe bleeding. We refined this model using data from existing animal studies to ensure our simulations were accurate. We also used patient data to further refine the simulations to accurately predict which patients would live and which would not. We studied the effects of different treatment protocols on these simulated patients and show that treatment with plasma (the fluid portion of blood that helps form blood clots) and red blood cells jointly, gave better results than treatment with intravenous fluid or plasma alone. Early treatment with plasma reduced injury severity and increased survival time. This modelling approach may improve our ability to evaluate new treatments for trauma-associated bleeding and other acute conditions.

Extreme γ' fibrinogen levels in COVID-19 patients.

COVID-19 disease progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.

Implementing thrombelastography: Experiences from a level I trauma institution.

Viscoelastic hemostatic assays such as thrombelastography (TEG) and rotational thrombelastometry have proven to be important point-of-care tools in the management of acute traumatic hemorrhage. Despite the availability of prospective studies that have confirmed the utility of TEG in reducing transfusion requirements and mortality in bleeding patients when compared to conventional coagulation tests, many institutions run into barriers implementing these viscoelastic hemostatic assays due to concerns regarding cost and benefit. At our academic Level 1 trauma institution, the Division of Trauma, Critical Care, and Acute Care Surgery advocated for the addition of TEG to the clinical armamentarium of providers caring for injured patients and thus spearheaded the clinical implementation of TEG. With the approval of the central laboratory, the Division developed an extensive and well-trained team to run and interpret TEGs as well as perform machine validation and upkeep. The Division continues to perform point-of-care testing throughout the hospital today.

Use of bilobed partial resuscitative endovascular balloon occlusion of the aorta is logistically superior in prolonged management of a highly lethal aortic injury.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable technique for management of noncompressible torso hemorrhage. The major limitation of the current unilobed fully occlusive REBOA catheters is below-the-balloon ischemia-reperfusion complications. We hypothesized that partial aortic occlusion with a novel bilobed partial (p)REBOA-PRO would result in the need for less intraaortic balloon adjustments to maintain a distal goal perfusion pressure as compared with currently available unilobed ER-REBOA. METHODS: Anesthetized (40-50 kg) swine randomized to control (no intervention), ER-REBOA, or pREBOA-PRO underwent supraceliac aortic injury. The REBOA groups underwent catheter placement into zone 1 with initial balloon inflation to full occlusion for 10 minutes followed by gradual deflation to achieve and subsequently maintain half of the baseline below-the-balloon mean arterial pressure (MAP). Physiologic data and blood samples were collected at baseline and then hourly. At 4 hours, the animals were euthanized, total blood loss and urine output were recorded, and tissue samples were collected. RESULTS: Baseline physiologic data and basic laboratories were similar between groups. Compared with control, interventions similarly prolonged survival from a median of 18 minutes to over 240 minutes with comparable mortality trends. Blood loss was similar between partial ER-REBOA (41%) and pREBOA-PRO (51%). Partial pREBOA-PRO required a significantly lower number of intraaortic balloon adjustments (10 ER-REBOA vs. 3 pREBOA-PRO, p < 0.05) to maintain the target below-the-balloon MAP. The partial ER-REBOA group developed significantly increased hypercapnia, fibrin clot formation on TEG, liver inflammation, and IL-10 expression compared with pREBOA-PRO. CONCLUSION: In this highly lethal aortic injury model, use of bilobed pREBOA-PRO for a 4-hour partial aortic occlusion was logistically superior to unilobed ER-REBOA. It required less intraaortic balloon adjustments to maintain target MAP and resulted in less inflammation.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

BACKGROUND: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients. METHODS: Two hundred forty-three trauma patients at five Level I trauma centers who required RBC transfusion were randomized to receive one to two units of liquid packed RBCs (LPRBCs) or CPRBCs. Demographics, injury severity, StO2, outcomes, and biomarkers of RBC function were compared in nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) patients. StO2 was also compared between obese patients with BMI of 30 to 34.9 and BMI ≥ 35. StO2 was normalized and expressed as % change after RBC transfusion. A p value less than 0.05 indicated significance. RESULTS: Patients with BMI less than 30 (n = 141) and BMI of 30 or greater (n = 102) had similar Injury Severity Score, Glasgow Coma Scale, and baseline StO2. Plasma levels of free hemoglobin, an index of RBC lysis, were lower in obese patients after CPRBC (125 [72-259] µg/mL) versus LPRBC transfusion (230 [178-388] µg/mL; p < 0.05). StO2 was similar in nonobese patients regardless of transfusion type, but improved in obese patients who received CPRBCs (104 ± 1%) versus LPRPCs (99 ± 1%, p < 0.05; 8 hours after transfusion). Subanalysis showed improved StO2 after CPRBC transfusion was specific to BMI of 35 or greater, starting 5 hours after transfusion (p < 0.05 vs. LPRBCs). CPRBCs did not improve clinical outcomes in either group. CONCLUSION: CPRBC transfusion is associated with increased StO2 and lower free hemoglobin levels in obese trauma patients, but did not improve clinical outcomes. Future studies are needed to determine if CPRBC transfusion in obese patients attenuates hemolysis to improve StO2. LEVEL OF EVIDENCE: Therapeutic, level IV.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial.

OBJECTIVES: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.

Splenectomy is associated with hypercoagulable thrombelastography values and increased risk of thromboembolism.

BACKGROUND: Previous investigators have demonstrated that postinjury thrombocytosis is associated with an increase in thromboembolic (TE) risk. Increased rates of thrombocytosis have been found specifically in patients after splenectomy for trauma. We hypothesized that patients undergoing splenectomy (1) would demonstrate a more hypercoagulable profile during their hospital stay and (2) that this hypercoagulable state would be associated with increased TE events. METHODS: This was a 14-month, prospective, observational trial evaluating serial rapid thrombelastography (rTEG) at 3 American College of Surgeons-verified, level 1 trauma centers. Inclusion criteria were highest-level trauma activation and arrival within 6 hours of injury. Exclusion criteria were <18 years of age, incarcerated, and burns>20% total body surface area. Serial rTEG (activated clotting time, k-time, α-angle, MA, lysis) and traditional coagulation testing (prothrombin time, partial thromboplastin time, fibrinogen and platelet count) were obtained at admission and then at 3, 6, 12, 24, 48, 72, 96, and 120 hours. Thromboembolic complications were defined as the development of deep-vein thrombosis, pulmonary embolism, acute myocardial infarction, or ischemic stroke during hospitalization. Patients were stratified into splenectomy versus nonsplenectomy cohorts. Univariate analysis was then conducted followed by longitudinal analysis using generalized estimating equations to evaluate the effects of time, splenectomy, and group-time interactions on changes in rTEG and traditional coagulation testing. We used an adjusted generalized estimating equation model to control for age, sex, ISS, admission blood pressure, base deficit, and hemoglobin. RESULTS: A total of 1,242 patients were enrolled; 795 had serial rTEG data. Of these, 605 had serial values >24 hours and made up the study population. Splenectomy patients were younger, more hypotensive, and in shock on arrival. Although there was no difference in 24-hour or 30-day mortality, splenectomy patients were more likely to develop TE events. Using the GEE model, we found that α-angle and MA in splenectomy patients were lesser (more hypocoagulable) within the first 6 hours; however, they became substantially greater (more hypercoagulable) at 48, 72, 96, and 120 hours; all P < .05. In addition, platelet counts were greater in the splenectomy group beginning at 72 hours and continuing through 120 hours; P < .05. CONCLUSION: This multicenter, prospective study demonstrates that patients undergoing splenectomy have a more hypercoagulable state than other trauma patients. This hypercoagulable state (identified by greater α-angle and mA values) begins at approximately 48 hours after injury and continues through at least day 5. Moreover, this hypercoagulable state is associated with increased risk of TE complications.

Moderate elevations in international normalized ratio should not lead to delays in neurosurgical intervention in patients with traumatic brain injury.

BACKGROUND: The management of severe traumatic brain injury (TBI) frequently involves invasive intracranial monitoring or cranial surgery. In our institution, intracranial procedures are often deferred until an international normalized ratio (INR) of less than 1.4 is achieved. There is no evidence that a moderately elevated INR is associated with increased risk of bleeding in patients undergoing neurosurgical intervention (NI). Thrombelastography (TEG) provides a functional assessment of clotting and has been shown to better predict clinically relevant coagulopathy compared with INR. We hypothesized that in patients with TBI, an elevated INR would result in increased time to NI and would not be associated with coagulation abnormalities based on TEG. METHODS: A secondary analysis of prospectively collected data was performed in trauma patients with intracranial hemorrhage that underwent NI (defined as cranial surgery or intracranial pressure monitoring) within 24 hours of arrival. Time from admission to NI was recorded. TEG and routine coagulation assays were obtained at admission. Patients were considered hypocoagulable based on INR if their admission INR was greater than 1.4 (high INR). Manufacturer-specified values were used to determine hypocoagulability for each TEG variable. RESULTS: Sixty-one patients (median head Abbreviated Injury Scale [AIS] score, 5) met entry criteria, of whom 16% had high INR. Demographic, physiologic, and injury scoring data were similar between groups. The median time to NI was longer in patients with high INR (358 minutes vs. 184 minutes, p = 0.027). High-INR patients were transfused more plasma than patients with an INR of 1.4 or less (2 U vs. 0 U, p = 0.01). There was no association between an elevated INR and hypocoagulability based on TEG. CONCLUSION: TBI patients with an admission INR of greater than 1.4 had a longer time to NI. The use of plasma transfusion to decrease the INR may have contributed to this delay. A moderately elevated INR was not associated with coagulation abnormalities based on TEG. Routine plasma transfusion to correct a moderately elevated INR before NI should be reexamined. LEVEL OF EVIDENCE: Diagnostic study, level III.

Cryopreserved red blood cells are superior to standard liquid red blood cells.

BACKGROUND: Liquid preserved packed red blood cell (LPRBC) transfusions are used to treat anemia and increase end-organ perfusion. Throughout their storage duration, LPRBCs undergo biochemical and structural changes collectively known as the storage lesion. These changes adversely affect perfusion and oxygen off-loading. Cryopreserved RBCs (CPRBC) can be stored for up to 10 years and potentially minimize the associated storage lesion. We hypothesized that CPRBCs maintain a superior biochemical profile compared with LPRBCs. METHODS: This was a prospective, randomized, double-blinded study. Adult trauma patients with an Injury Severity Score (ISS) greater than 4 and an anticipated 1-U to 2-U transfusion of PRBCs were eligible. Enrolled patients were randomized to receive either CPRBCs or LPRBCs. Serum proteins (haptoglobin, serum amyloid P, and C-reactive protein), proinflammatory and anti-inflammatory cytokines, d-dimer, nitric oxide, and 2,3-DPG concentrations were analyzed. Mann-Whitney U-test and Wilcoxon rank sum test were used to assess significance (p < 0.05). RESULTS: Fifty-seven patients were enrolled (CPRBC, n = 22; LPRBC, n = 35). The LPRBC group's final interleukin 8, tumor necrosis factor α, and d-dimer concentrations were elevated compared with their pretransfusion values (p < 0.05). After the second transfused units, 2,3-DPG was higher in the patients receiving CPRBCs (p < 0.05); this difference persisted throughout the study. Finally, serum protein concentrations were decreased in the transfused CPRBC units compared with LPRBC (p < 0.01). CONCLUSION: CPRBC transfusions have a superior biochemical profile: an absent inflammatory response, attenuated fibrinolytic state, and increased 2,3-DPG. A blood banking system using both storage techniques will offer the highest-quality products to critically injured patients virtually independent of periodic changes in donor availability and transfusion needs. LEVEL OF EVIDENCE: Therapeutic study, level II.

The international normalized ratio overestimates coagulopathy in patients after major hepatectomy.

BACKGROUND: The International Normalized Ratio (INR) is commonly used to guide therapy after hepatectomy. We hypothesized that the use of thrombelastography (TEG) would demonstrate a decreased incidence of hypocoagulability in this patient population. METHODS: Seventy-eight patients were prospectively enrolled before undergoing hepatectomy. INR, TEG, and coagulation factors were drawn before incision, postoperatively, and on postoperative days 1, 3, and 5. RESULTS: Patients demonstrated an elevated INR at all postoperative time points. However, TEG demonstrated a decreased R value postoperatively, with subsequent normalization. Other TEG measurements were equivalent to preoperative values. All procoagulant factors save factor VIII decreased postoperatively, with a simultaneous decrease in protein C. CONCLUSIONS: TEG demonstrated a brief hypercoagulable state after major hepatectomy, with coagulation subsequently normalizing. The INR significantly overestimates hypocoagulability after hepatectomy and these data call into question current practices using the INR to guide therapy in this patient population.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

BACKGROUND: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. METHODS: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. RESULTS: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. CONCLUSION: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

Correlation of missed doses of enoxaparin with increased incidence of deep vein thrombosis in trauma and general surgery patients.

IMPORTANCE: Enoxaparin sodium is widely used for deep vein thrombosis (DVT) prophylaxis, yet DVT rates remain high in the trauma and general surgery populations. Missed doses during hospitalization are common. OBJECTIVE: To determine if missed doses of enoxaparin correlate with DVT formation. DESIGN, SETTING, AND PARTICIPANTS: Data were prospectively collected among 202 trauma and general surgery patients admitted to a level I trauma center. MAIN OUTCOMES AND MEASURES: Deep vein thrombosis screening was performed using a rigorous standardized protocol. RESULTS: The overall incidence of DVT was 15.8%. In total, 58.9% of patients missed at least 1 dose of enoxaparin. The DVTs occurred in 23.5% of patients who missed at least 1 dose and in 4.8% of patients who did not (P < .01). On univariate analysis, the need for mechanical ventilation (71.8% vs 44.1%), the performance of more than 1 operation (59.3% vs 40.0%), and male sex (75% vs 56%) were associated with DVT formation (P < .05 for all). A bivariate logistic regression was then performed, which revealed age 50 years or older and interrupted enoxaparin therapy as the only independent risk factors for DVT formation. The DVT rate did not differ between trauma and general surgery populations or in patients receiving once-daily vs twice-daily dosing regimens. CONCLUSIONS AND RELEVANCE: Interrupted enoxaparin therapy and age 50 years or older are associated with DVT formation among trauma and general surgery patients. Missed doses occur commonly and are the only identified risk factor for DVT that can be ameliorated by physicians. Efforts to minimize interrupted enoxaparin prophylaxis in patients at risk for DVT should be optimized.

Prehospital intravenous fluid is associated with increased survival in trauma patients.

BACKGROUND: Delivery of intravenous crystalloid fluids (IVF) remains a tradition-based priority during prehospital resuscitation of trauma patients. Hypotensive and targeted resuscitation algorithms have been shown to improve patient outcomes. We hypothesized that receiving any prehospital IVF is associated with increased survival in trauma patients compared with receiving no prehospital IVF. METHODS: Prospective data from 10 Level 1 trauma centers were collected. Patient demographics, prehospital IVF volume, prehospital and emergency department vital signs, lifesaving interventions, laboratory values, outcomes, and complications were collected and analyzed. Patients who did or did not receive prehospital IVF were compared. Tests for nonparametric data were used to assess significant differences between groups (p ≤ 0.05). Cox regression analyses were performed to determine the independent influence of IVF on outcome and complications. RESULTS: The study population consisted of 1,245 trauma patients; 45 were excluded owing to incomplete data; 84% (n = 1,009) received prehospital IVF, and 16% (n = 191) did not. There was no difference between the groups with respect to sex, age, and Injury Severity Score (ISS). The on-scene systolic blood pressure was lower in the IVF group (110 mm Hg vs. 100 mm Hg, p < 0.04) and did not change significantly after IVF, measured at emergency department admission (110 mm Hg vs. 105 mm Hg, p = 0.05). Hematocrit/hemoglobin, fibrinogen, and platelets were lower (p < 0.05), and prothrombin time/international normalized ratio and partial thromboplastin time were higher (p < 0.001) in the IVF group. The IVF group received a median fluid volume of 700 mL (interquartile range, 300-1,300). The Cox regression revealed that prehospital fluid administration was associated with increased survival (hazard ratio, 0.84; 95% confidence interval, 0.72-0.98; p = 0.03). Site differences in ISS and fluid volumes were demonstrated (p < 0.001). CONCLUSION: Prehospital IVF volumes commonly used by PRospective Observational Multicenter Massive Transfusion Study (PROMMTT) investigators do not result in increased systolic blood pressure but are associated with decreased in-hospital mortality in trauma patients compared with patients who did not receive prehospital IVF.

Correlation of conventional thrombelastography and rapid thrombelastography in trauma.

BACKGROUND: Conventional thrombelastography has been in use for over 6 decades and provides a functional assay of coagulation. Rapid thrombelastography was developed to provide more rapid comprehensive analysis of coagulation status in an emergency setting. The purpose of this study was to determine the correlation of rapid thrombelastographic values with conventional thrombelastographic values in trauma patients. METHODS: We performed a prospective study on trauma patients at a university level 1 trauma center. Conventional thrombelastography and rapid thrombelastography were performed on 190 consecutive major trauma patients upon admission between 2010 and 2012. Conventional thrombelastographic and rapid thrombelastographic parameters were analyzed using bivariate analysis with Pearson correlation. Group comparisons were performed using the Mann-Whitney U test. RESULTS: Patients were predominantly male (71.6%, P < .05) with a median Injury Severity Score of 17 (range 10 to 29) and a median age of 43 years (range 29 to 53 years). There were significantly more patients with blunt trauma than penetrating trauma (72% vs 28%, P < .05). There was a strong correlation between the rapid thrombelastographic and conventional thrombelastographic maximal amplitude value, which represents platelet function (r = .80). There was a moderate correlation between the G (overall clot strength, r = .70), k (speed of clot formation, r = .66), and α-angle (r = .38), which reflects the degree of fibrin cross-linking. Lysis at 30 minutes correlated poorly (r = .19). CONCLUSIONS: Overall, there is a strong correlation between rapid thrombelastography and conventional thrombelastography in terms of overall clot strength and platelet function. There is a moderate correlation in assessing the degree of fibrin cross-linking and a poor correlation in evaluating thrombolysis. These correlations should be considered when evaluating coagulation status using rapid thrombelastography.

Coagulopathy after a liver resection: is it over diagnosed and over treated?

BACKGROUND: Prothrombin time-international normalized ratio (PT-INR) is widely utilized to guide plasma therapy and initiation of thromboprophylaxis after a hepatectomy. Thrombelastography (TEG) monitors shear elasticity, which is sensitive to cellular and plasma components in blood, allowing for functional assessment of the life of the clot. The objective of this study was to prospectively compare PT-INR and TEG in liver resection patients. METHODS: Forty patients were enrolled before undergoing an elective hepatectomy. Patients underwent a liver resection utilizing a low central venous pressure (CVP) anaesthetic technique and intermittent Pringle manoeuver. PT-INR and TEG were drawn prior to incision, post-operatively, and post-operative days 1, 3 and 5. RESULTS: All post-operative PT-INR values increased significantly when compared with pre-operative PT-INR (P < 0.01). The time of onset to clot (R-value) decreased significantly at the post-operative time point (P = 0.04), consistent with a relative hypercoagulability. Subsequent R-values were not different compared with the pre-operative R-value. The strength of the clot (maximum amplitude, MA) was unchanged when comparing pre- and post-operative time points. DISCUSSION: In spite of an elevation in PT-INR, patients undergoing a liver resection demonstrated a brief hypercoagulable state, followed by normal coagulation function based on TEG. These data call into question the practice of utilizing PT-INR to guide plasma transfusion and timing of prophylactic anticoagulation after a liver resection.

Cryopreserved deglycerolized blood is safe and achieves superior tissue oxygenation compared with refrigerated red blood cells: a prospective randomized pilot study.

BACKGROUND: During preservation, donated liquid red blood cells (RBCs) experience multiple functional and structural changes known as the storage lesion. Increased RBC age is associated with increased infection rates, organ failure, and mortality. METHODS: This prospective, randomized, double-blinded pilot study enrolled stable trauma patients who required RBC transfusion. Patients were randomly assigned to receive standard or cryopreserved RBCs. Continuous tissue oxygenation (StO2) monitoring was performed during the peritransfusion period. Hematocrit and thrombelastography before and after transfusion were evaluated. Patients were monitored for transfusion reactions and clinical outcomes. RESULTS: Fifty-seven patients were randomized, and groups were well matched for demographics and Injury Severity Score (ISS). No statistically significant differences were noted in hematocrit change, thrombelastography parameters, transfusion reactions, or clinical outcomes. StO2 was found to be higher in the cryopreserved group. CONCLUSION: Cryopreserved RBCs are equally safe and efficacious to refrigerated RBCs. This storage technique extends the life span of RBCs to 10 years, potentially preserving a precious resource and preventing the storage lesion. StO2 was superior in patients receiving cryopreserved RBCs. This finding has the potential to drive a paradigm shift in transfusion practices. LEVEL OF EVIDENCE: Therapeutic study, level II.

The effects of location and low-molecular-weight heparin administration on deep vein thrombosis outcomes in trauma patients.

BACKGROUND: Deep vein thrombosis (DVT) is common after trauma. Pulmonary embolism (PE) is a feared complication of DVT. Standard doses of low-molecular-weight heparin (LMWH) are commonly used to prevent and treat DVT and PE. There is variable bioavailability of LMWH with standard therapy. The traditional concept that below-knee DVT is associated with a lower risk of subsequent PE may result in less aggressive therapy. The purposes of this study were to assess the rates of PE in above-knee versus below-knee DVT and longitudinally evaluate outcomes of DVT treated with LMWH therapy. METHODS: This was a retrospective review of patients at a university Level I trauma center during the years 2005 through 2010. Patients diagnosed with lower-extremity DVT were included in this study. Patients were classified by location of lower-extremity DVT and type of LMWH therapy received. All high-risk trauma patients were evaluated with weekly duplex Doppler ultrasonography. All duplex studies were reviewed for DVT resolution or improvement. Symptomatic patients were evaluated with computed tomographic angiography to rule out PE. Demographics, total length of hospital stay, length of intensive care unit stay, and Injury Severity Score (ISS) were collected. RESULTS: Three-hundred eight trauma patients with lower-extremity DVT were included. More patients developed below-knee DVT (65.6%) compared with above-knee DVT (34.4%). Increased length of hospital stay, intensive care unit stay, and higher ISS were noted in patients with above-knee DVT. More patients had below-knee DVT in the prophylactic dosing group. With LMWH therapy, three PEs occurred in patients in the prophylactic dosing group with below-knee DVT, and no PEs occurred in the therapeutic treatment group. The incidence of PE between patients with below-knee DVT compared with above-knee DVT overall was not different (3.3% and 4.7%, p = 0.59). To assess DVT outcomes, 157 of the 308 patients had serial duplex studies following diagnosis of lower-extremity DVT. The number of patients receiving either therapeutic or prophylactic LMWH was similar (51% and 49%). There was no difference in rates of resolution or improvement between LMWH dosing groups or location of DVT. CONCLUSION: In screened trauma patients, below-knee DVT is more common than above-knee DVT. There was no difference in the incidence of PE between groups. Standard prophylactic and therapeutic dosing of LMWH does not affect the rates of resolution or improvement of lower-extremity DVT. Rates of resolution and improvement of DVT is not dependent of location of lower-extremity DVT. LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemiologic study, level III.

Management of the open abdomen during the global war on terror.

OBJECTIVE: To evaluate factors that are predictive of delayed abdominal closure in patients injured during military conflict. DESIGN, SETTING, AND PATIENTS: Seventy-one patients managed with an open abdomen were identified from records at Landstuhl Regional Medical Center from 2005 and 2006. Follow-up data were available from Walter Reed Army Medical Center. Records were reviewed through all echelons of care. Ordinal logistic regression was used to predict delayed abdominal closure. RESULTS: Patients sustained injury from blunt (n = 2), penetrating (n = 30), and blast (n = 39) mechanisms. The median Injury Severity Score was 25 (interquartile range, 17-34). Abdominal injury was observed in 85% of patients, and 48% underwent a massive transfusion. The median time to transfer to the United States was 5.3 days (interquartile range, 4.3-6.8 days). Abdomens were definitively closed downrange (11%), at Landstuhl Regional Medical Center (33%), or at Walter Reed Army Medical Center (56%). The median time until abdominal closure was 13 days (interquartile range, 4-40 days) in 2005 compared with 4 days (interquartile range, 1-14.5 days) in 2006 (P = .02). The multivariate model identified massive transfusion (odds ratio, 3.9), presence of complications (odds ratio, 5.1), and an injury date in 2005 (odds ratio, 3.4) as independently predictive variables for later abdominal closure. CONCLUSIONS: Massive transfusion, occurrence of complications, and earlier injury date were predictive of delayed abdominal closure in casualties managed with an open abdomen. These data suggest an evolving approach to the management of severely injured combat casualties that involves earlier abdominal closure.

Trauma induces a hypercoagulable state that is resistant to hypothermia as measured by thrombelastogram.

BACKGROUND: The aim of this study was to test the hypothesis that severely injured trauma patients would be hypercoagulable compared with controls measured by thromboelastography and that this hypercoagulability would persist over a broad range of temperatures. METHODS: A prospective study evaluating the effects of temperature on coagulation in trauma patients with Injury Severity Scores ≥ 15 and controls was completed. Thromboelastography was performed 24 hours after admission at 4 temperatures ranging from 32°C to 38°C. RESULTS: Ninety-two subjects (46 patients) were analyzed. Patients had a median Injury Severity Score of 20 (interquartile range, 16­26). Time to clot formation increased (P < .001) and fibrin cross-linking decreased (P < .01) in both groups as temperature decreased. Between groups, time to clot formation, fibrin cross-linking, and clot strength were significantly different at each temperature (P < .01), with patients being more hypercoagulable. Time to clot formation and fibrin cross-linking were more affected by temperature in controls compared with patients (P < .02). CONCLUSIONS: Severely injured patients are more hypercoagulable than controls throughout a broad range of temperature. Decreasing temperature has a greater effect on coagulation in controls compared with patients.