The effect of shock duration on trauma-induced coagulopathy in a murine model

Background Trauma-induced coagulopathy (TIC) is a life-threatening condition associated with high morbidity and mortality. TIC can present with different coagulation defects. In this study, the aim was to determine the effect of shock duration on TIC characteristics. We hypothesized that longer duration of shock leads to a more hypocoagulable rotational thromboelastometry (ROTEM) profile compared to a shorter duration of shock. Methods Male B57BL/6J(c) mice (n = 5–10 per group) were sedated and mechanically ventilated. Trauma was induced by bilateral lower limb fractures and crush injuries to the liver and small intestine. Shock was induced by blood withdrawals until a mean arterial pressure of 25–30 mmHg was achieved. Groups reflected trauma and shock for 30 min (TS30) and trauma and shock for 90 min (TS90). Control groups included ventilation only (V90) and trauma only (T90). Results Mice in the TS90 group had significantly increased base deficit compared to the V90 group. Mortality was 10% in the TS30 group and 30% in the TS90 group. ROTEM profile was more hypocoagulable, as shown by significantly lower maximum clot firmness (MCF) in the TS30 group (43.5 [37.5–46.8] mm) compared to the TS90 group (52.0 [47.0–53.0] mm, p = 0.04). ROTEM clotting time and parameters of clot build-up did not significantly differ between groups. Conclusions TIC characteristics change with shock duration. Contrary to the hypothesis, a shorter duration of shock was associated with decreased maximum clotting amplitudes compared to a longer duration of shock. The effect of shock duration on TIC should be further assessed in trauma patients.

Personalized modulation of coagulation factors using a thrombin dynamics model to treat trauma-induced coagulopathy

Current trauma-induced coagulopathy resuscitation protocols use slow laboratory measurements, rules-of-thumb, and clinician gestalt to administer large volumes of uncharacterized, non-tailored blood products. These one-size-fits-all treatment approaches have high mortality. Here, we provide significant evidence that trauma patient survival 24 h after hospital admission occurs if and only if blood protein coagulation factor concentrations equilibrate at a normal value, either from inadvertent plasma-based modulation or from innate compensation. This result motivates quantitatively guiding trauma patient coagulation factor levels while accounting for protein interactions. Toward such treatment, we develop a Goal-oriented Coagulation Management (GCM) algorithm, a personalized and automated ordered sequence of operations to compute and specify coagulation factor concentrations that rectify clotting. This novel GCM algorithm also integrates new control-oriented advancements that we make in this work: an improvement of a prior thrombin dynamics model that captures the coagulation process to control, a use of rapidly-measurable concentrations to help predict patient state, and an accounting of patient-specific effects and limitations when adding coagulation factors to remedy coagulopathy. Validation of the GCM algorithm’s guidance shows superior performance over clinical practice in attaining normal coagulation factor concentrations and normal clotting profiles simultaneously.

Trauma-induced coagulopathy: prospective observation study

Coagulopathy remains the leading cause of illness and death in people with severe trauma. The aim was to study the indicators of vascular-platelet hemostasis in severe trauma and to establish changes in the main pathophysiological mechanisms of primary hemostasis that occur in patients with trauma-induced coagulopathy, compared with almost healthy individuals of the same age. Materials and methods. The study included 44 patients aged 19 to 55 years (36.1 [28.7; 43.2] years). The control group included 20 patients of the therapeutic department without preconditions for changes in the hemostasis system, and the main group - 24 patients with diagnosis of “severe trauma” who were treated in the anesthesiology and intensive care department. Results and discussion. We studied indicators of intravascular platelet activation. Patients had a normal number of platelets in the venous blood, but the level of spherocytes and spheroechinocytes increased. On the 3rd day after the injury, number of platelets in the venous blood was normal, however the level of discocytes decreased, and the level of discochinocytes, spheroechinocytes and the sum of active forms of platelets increased. On the fifth day, the level of discochinocytes and active forms of platelets, significantly higher (p<0.05) among patients of the main group, and spherocytes, spheroechinocytes and platelets involved in the aggregates, were significantly lower than in the control group of patients (p<0.05). Conclusions. Indicators of vascular-platelet hemostasis in patients with polytrauma had significant differences from those of the control group. This may be evidence of activation of the vascular-platelet system of the hemostasis system and may be a prerequisite for late thrombotic complications in patients with polytrauma