Abstract

BACKGROUND No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE Diagnostic test, level III.

Abstract

BACKGROUND No FDA-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS Data were extracted from a placebo-controlled clinical trial in which patients ≥15 years old with TBI (Glascow Coma Scale 3-12) and systolic blood pressure ≥90 mmHg were randomized prehospital to receive placebo bolus/placebo infusion (Placebo), 1 gram (g) TXA bolus/1g TXA infusion (Bolus Maintenance [BM]); or 2g TXA bolus/placebo infusion (Bolus Only [BO]). TEG was performed and coagulation measures including prothrombin time (PT), activated partial thromboplastin time (aPTT), international ratio (INR), fibrinogen, D-dimer, plasmin anti-plasmin (PAP), thrombin anti-thrombin (TAT), tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were quantified at admission and six hours later. RESULTS Of 966 patients receiving study drug, 700 had labs drawn at admission and six hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p>0.05). No differences between PT, aPTT, INR, fibrinogen, TAT, tPA, and PAI-1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at six hours (p<0.001). Concentrations of PAP were less in TXA treatment groups than placebo on admission (p<0.001) and six hours (p=0.02). No differences in D-dimer and PAP were observed between BM and BO. CONCLUSION While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared to placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and six hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE III; Diagnostic.

Abstract

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] mug/mL) versus LPRBC transfusion (230 [178-388] mug/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.

Abstract

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 alpha2-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.