Gender Differences in Hypothermia-associated Coagulopathy in Alpine Multiple Trauma Patients – Combined epidemiological and experimental prospective in-vitro Study

Introduction:

Hypothermia with acidosis and coagulopathy is part of the lethal triad in trauma and accounts for the high mortality in multiple trauma patients in mountain and remote environments. Gender differences in coagulation are prominent in fibrinogen synthesis and in the function of platelets. The detrimental effects of hypothermia on coagulation are exerted by inhibition of the mobility, aggregation of platelets and a decreases clot formation and clot firmness. The aim of this combined clinical and experimental study was to identify the impact of hypothermia on various components of the coagulation system.

Methods:

The International Alpine Trauma Registry (IATR) is a prospective multi-centre data base which records data of multiple trauma patients rescued from mountain and remote areas. An exploratory data analysis included multinomial logistic regression and One-way ANOVA. Secondly, we performed an in-vitro analysis of blood samples from 18 healthy volunteers, cooled to five different temperatures, ROTEM- and Multiplate-analysis was performed at each stage.

Results:

104 patients (15.4% female) were included, core temperature was 31.0°C±5.3°C. 32 patients (58.2%) were hypothermic (=35.0°C). Hypothermia compared to normothermia was associated with an INR>1.3 (82.4% vs 17.6% p=0.025). Women were less severely traumatized (p=0.01) and experienced a shorter pre-hospital time (p=0.01). The in-vitro data of nine females and nine males revealed in ExTEM a prolonged CT (CT_37.0°C 67.3±2.8sec; CT_13.7°C 134.1±8.8sec) and in FibTEM a reduced MCF (MCF_37.0°C 17.0±1.2mm; MCF_13.7°C 11.8±0.8mm). In females i) fibrinogen function was increased (MCF_female 19.0±1.6mm; MCF_male 14.2±0.9mm) and ii) platelet count lower. In profound hypothermia Multiplate revealed complete loss of platelet function (AUC_13.7°C and AUC_18.0°C 0%).

Conclusion:

Gender-specific differences were shown in the alpine multiple trauma with lower ISS and but greater risk of prehospital heat-loss despite shorter prehospital times. The in-vitro-study showed an impairment of cellular and humoral coagulation in ROTEM and Multiplate. While women start with high levels of fibrinogen but lower platelet counts we were not able to detect significant differences in the reaction to hypothermia. In the treatment of multiple trauma, a greater emphasis must be put on Gender-specific differences and treatment must be adapted accordingly.