Sarah A. Eidelson

INCREASED RISK OF FIBRINOLYSIS SHUTDOWN AMONG SEVERELY INJURED TRAUMA PATIENTS RECEIVING TRANEXAMIC ACID

BACKGROUND The association between tranexamic acid (TXA) and fibrinolysis shutdown is unknown. We hypothesize that TXA is associated with fibrinolysis shutdown in critically injured trauma patients. METHODS Two hundred eighteen critically injured adults admitted to the intensive care unit at an urban Level I trauma center from August 2011 to January 2015 who had thromboelastography performed upon intensive care unit admission were reviewed. Groups were stratified based on fibrinolysis shutdown, which was defined as LY30 of 0.8% or less. Continuous variables were expressed as mean ± standard deviation or median (interquartile range). Poisson regression analysis was used to determine predictors of shutdown. RESULTS Patients were age 46 ± 18 years, 81% male, 75% blunt trauma, Injury Severity Score of 28 ± 13, 16% received TXA, 64% developed fibrinolysis shutdown, and mortality was 15%. In the first 24 hours, 4 (2–9) units packed red blood cells and 2 (0–6) units fresh frozen plasma were administered. Those with shutdown had worse initial systolic blood pressure (114 ± 38 mm Hg vs. 129 ± 43 mm Hg, p = 0.006) and base deficit (−5 ± 6 mEq/L vs −3 ± 5 mEq/L, p = 0.013); received more packed red blood cells [6 (2–11) vs. 2 (1–5) units, p < 0.0001], and fresh frozen plasma [3 (0–8) vs. 0 (0–4) units, p < 0.0001]; and more often received TXA (23% vs. 4%, p <0.0001). After controlling for confounders, TXA (relative risk, 1.35; 95% confidence interval, 1.10–1.64; p = 0.004) and cryoprecipitate transfusion (relative risk, 1.29; 95% confidence interval, 1.07–1.56; p = 0.007) were independently associated with fibrinolysis shutdown. CONCLUSION Patients who received TXA were at increased risk of fibrinolysis shutdown compared with patients who did not receive TXA. We recommend that administration of TXA be limited to severely injured patients with evidence of hyperfibrinolysis and recommend caution in those with evidence of fibrinolysis shutdown. LEVEL OF EVIDENCE Therapeutic, level III.

Association of Anti–Factor Xa–Guided Dosing of Enoxaparin With Venous Thromboembolism After Trauma

Importance The efficacy of anti–factor Xa (anti-Xa)–guided dosing of thromboprophylaxis after trauma remains controversial. Objective To assess whether dosing of enoxaparin sodium based on peak anti-Xa levels is associated with the venous thromboembolism (VTE) rate after trauma. Design, Setting, and Participants Retrospective review of 950 consecutive adults admitted to a single level I trauma intensive care unit for more than 48 hours from December 1, 2014, through March 31, 2017. Within 24 hours of admission, these trauma patients were screened with the Greenfield Risk Assessment Profile (RAP) (possible score range, 0-46). Patients younger than 18 years and those with VTE on admission were excluded, resulting in a study population of 792 patients. Exposures The control group received fixed doses of either heparin sodium, 5000 U 3 times a day, or enoxaparin sodium, 30 mg twice a day. The adjustment cohort initially received enoxaparin sodium, 30 mg twice a day. A peak anti-Xa level was drawn 4 hours after the third dose. If the anti-Xa level was 0.2 IU/mL or higher, no adjustment was made. If the anti-Xa level was less than 0.2 IU/mL, each dose was increased by 10 mg. The process was repeated up to a maximum dose of 60 mg twice a day. Main Outcomes and Measures Rates of VTE were measured. Venous duplex ultrasonography and computed tomographic angiography were used for diagnosis. Results The study population comprised 792 patients with a mean (SD) age of 46 (19) years and was composed of 598 men (75.5%). The control group comprised 570 patients, was older, and had a longer time to thromboprophylaxis initiation. The adjustment group consisted of 222 patients, was more severely injured, and had a longer hospital length of stay. The mean (SD) RAP scores were 9 (4) for the control group and 9 (5) for the adjustment group (P = .28). The VTE rates were similar for both groups (34 patients [6.0%] vs 15 [6.8%]; P = .68). Prophylactic anti-Xa levels were reached in 119 patients (53.6%) in the adjustment group. No difference in VTE rates was observed between those who became prophylactic and those who did not (7 patients [5.9%] vs 8 [7.8%]; P = .58). To control for confounders, 132 patients receiving standard fixed-dose enoxaparin were propensity matched to 84 patients receiving dose-adjusted enoxaparin. The VTE rates remained similar between the control and adjustment groups (3 patients [2.3%] vs 3 [3.6%]; P = .57). Conclusions and Relevance Rates of VTE were not reduced with anti-Xa–guided dosing, and almost half of the patients never reached prophylactic anti-Xa levels; achieving those levels did not decrease VTE rates. Thus, other targets, such as platelets, may be necessary to optimize thromboprophylaxis after trauma.

Relation of antifactor-Xa peak levels and venous thromboembolism after trauma

BACKGROUND No previous studies have established the optimal antifactor Xa (anti-Xa) level to guide thromboprophylaxis (TPX) dosing with enoxaparin in trauma patients. We hypothesize that achieving 0.2–0.4 IU/mL anti-Xa will decrease venous thromboembolism (VTE) rates after trauma. METHODS This was a retrospective review of 194 intensive care unit patients sustaining blunt or penetrating trauma from January 2015 to March 2017. All received initial enoxaparin (30 mg BID subcutaneous) and mechanical devices for TPX. Peak anti-Xa levels were drawn after each third dose. The enoxaparin dose was adjusted up to a maximum of 60 mg BID subcutaneous until a peak level of 0.2–0.4 IU/mL was achieved. Data are expressed as mean ± SD if parametric or median (IQR) if not. RESULTS The Greenfield Risk Assessment Profile score was 9 ± 4, Injury Severity Score 23 ± 14, and hospital length of stay 19 (11–38) days. The overall VTE rate was 7.2% (n = 14), with 10 deep venous thromboses (DVT) and 5 pulmonary emboli (PE). One patient had both a DVT and PE. The median time to VTE diagnosis was 14 (7–17) days. In those diagnosed with a VTE, 50.0% (n = 7) never reached 0.2–0.4 IU/mL anti-Xa and 42.8% (n = 6) were diagnosed with a VTE after achieving these levels. Prophylactic levels were achieved initially in 64 (33.0%) patients, and achieved later in 38 (19.6%) additional patients, giving an overall prophylactic rate of 52.6% (n = 102). There were no differences in VTE (6.9% vs. 7.6%, p = 0.841), DVT (3.9% vs. 6.5%, p = 0.413), or PE (3.9% vs. 1.1%, p = 0.213) rates between those who became prophylactic and those who did not. CONCLUSIONS There was no difference in VTE incidence between those achieving anti-Xa peak levels of 0.2–0.4 IU/mL and those who did not. Furthermore, these levels were never achieved in some trauma patients despite repeated dosing over a >10-day period. LEVEL OF EVIDENCE Therapeutic study, level IV.

1529: MECHANISM OF INJURY INFLUENCES TIMING OF VENOUS THROMBOEMBOLISM AFTER TRAUMA

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) coagulopathic bleeding. Anesthetized normothermic rabbits were hemodiluted 50– 60% by phased blood withdrawal and infusion of hydroxyethyl starch (HES) and erythrocytes. Bleeding was precipitated by a standardized kidney incision directly after (4F-PCC, 3F-PCC, aPCC, rFVIIa) or shortly before test item administration (4F-PCC). Results:Hemodilution resulted in coagulopathy (>1.5 fold prolongation of prothrombin time (PT), activated partial thromboplastin time (aPTT), whole blood clotting time (WBCT), and the rotational thromboelastography parameters EXTEM-CT and EXTEM-CFT, together with a reductions in FIBTEM-MCF to <2 mm). A significant increase in blood loss and time to hemostasis was observed following subsequent kidney incision. 4F-PCC treatment dose-dependently reduced bleeding signals and achieved maximum hemostatic control at dose levels of 25 IU/ kg in comparison to placebo treatment, independent of the timepoint of 4F-PCC administration (preor post injury). The efficacy of 4F-PCC was shown to be comparable to FEIBA (50U/kg) and improved as compared to 3F-PCCs (25IU/kg) or rFVIIa (90μg/kg). Conclusions: In summary, the in vivo rabbit model of coagulopathy and incision injury support the favorable efficacy profile of 4F-PCC.