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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. [ABSTRACT FROM AUTHOR]

Introduction: Evidence supports the use of plasma‐first resuscitation in the treatment of trauma‐induced coagulopathy (TIC). While thawed plasma (TP) has logistical benefits, the ability of plasma proteins to attenuate fibrinolysis and correct TIC remain unknown. We hypothesize that TP retains the ability to inhibit tissue plasminogen activator(tPA)‐induced fibrinolysis at 28‐day storage. Methods: Healthy volunteers underwent blood draws followed by 50% dilution of whole blood (WB) with TP at 28‐, 21‐, 14‐, 7‐, 5‐, and, 0‐day storage, normal saline (NS), and WB control. Samples underwent citrated tPA‐challenge (75 ng/ml) thromboelastography (TEG). Plasminogen activator inhibitor‐1 (PAI‐1) and α2‐antiplasmin (α2‐AP) concentrations in thawed or stored plasma were determined. Results: In the presence of tPA, 28‐day TP inhibited tPA‐induced coagulopathy as effectively as WB. 28‐day TP had a similar R‐time, MA, and fibrinolysis (P > 0·05 for all) compared to WB, while angle was enhanced (P = 0·02) compared to WB. Significant correlations were present between storage time and clot strength (P = 0·04) and storage time and fibrinolysis (P = 0·0029). Active PAI‐1 levels in thawed plasma were 1·10 ± 0·54 ng/mL while total PAI‐1 levels were 4·79 ± 1·41 ng/mL. There was no difference of α2‐AP levels in FFP (40·45 ± 3·5 μg/mL) compared to plasma thawed for 14 (36·78 ± 5·39 μg/mL, P = 0·65) or 28 days (45·16 ± 5·61 μg/mL, P = 0·51). Discussion: Thawed plasma retained the ability to inhibit tPA‐induced fibrinolysis over 28‐day storage at 1–4°C. α2‐AP levels were maintained in plasma thawed for 28 days and FFP. These in vitro results suggest consideration should be made to increasing the storage life of TP. [ABSTRACT FROM AUTHOR]

Antifibrinolytics, such as tranexamic acid (TXA), have been shown to improve outcomes in postinjury haemorrhagic shock.[[1]] However, several studies failed to confirm their benefit,[[3]] and several investigations suggest association with macro- and micro-thrombotic events (e.g. venous thromboembolic events (VTE) and acute lung injury (ALI)).[[2], [5], [7]] These data raised concerns over TXA's pre-emptive use without viscoelastic coagulation assays' (VCA) guidance. GLO:HWR/01apr20:ans15499-fig-0001.jpg PHOTO (COLOR): Predicted probability of fibrinolysis shutdown (with 95% confidence intervals) over hours postinjury in propensity score matched tranexamic acid (TXA) recipients and non-recipients. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. [Extracted from the article]