No abstract

Background Acute coagulopathy is a well-known predictor of poor outcomes in patients with severe trauma. However, using coagulation and fibrinolytic markers, how one can best predict mortality to find out potential candidates for treatment of coagulopathy remains unclear. This study aimed to determine preferential markers and their optimal cut-off values for mortality prediction. Methods We conducted a retrospective observational study of patients with severe blunt trauma (injury severity score ≥ 16) transferred directly from the scene to emergency departments at two trauma centres in Japan from January 2013 to December 2015. We investigated the impact and optimal cut-off values of initial coagulation (platelet counts, fibrinogen and prothrombin time-international normalised ratio) and a fibrinolytic marker (D-dimer) on 28-day mortality via classification and regression tree (CART) analysis. Multivariate logistic regression analysis confirmed the importance of these markers. Receiver operating characteristic curve analyses were used to examine the prediction accuracy for mortality. Results Totally 666 patients with severe blunt trauma were analysed. CART analysis revealed that the initial discriminator was fibrinogen (cut-off, 130 mg/dL) and the second discriminator was D-dimer (cut-off, 110 μg/mL in the lower fibrinogen subgroup; 118 μg/mL in the higher fibrinogen subgroup). The 28-day mortality was 90.0% (lower fibrinogen, higher D-dimer), 27.8% (lower fibrinogen, lower D-dimer), 27.7% (higher fibrinogen, higher D-dimer) and 3.4% (higher fibrinogen, lower D-dimer). Multivariate logistic regression demonstrated that fibrinogen levels < 130 mg/dL (adjusted odds ratio [aOR], 9.55; 95% confidence interval [CI], 4.50–22.60) and D-dimer ≥110 μg/mL (aOR, 5.89; 95% CI, 2.78–12.70) were independently associated with 28-day mortality after adjusting for probability of survival by the trauma and injury severity score (TRISS Ps). Compared with the TRISS Ps alone (0.900; 95% CI, 0.870–0.931), TRISS Ps with fibrinogen and D-dimer yielded a significantly higher area under the curve (0.942; 95% CI, 0.920–0.964; p < 0.001). Conclusions Fibrinogen and D-dimer were the principal markers for stratification of mortality in patients with severe blunt trauma. These markers could function as therapeutic targets because they were significant predictors of mortality, independent from severity of injury.

Hypothermia and acidosis are secondary causes of trauma-related coagulopathy. Here we report the case of a 72-year-old patient with severe trauma who suffered near-severe hypothermia despite the initiation of standard warming measures and was successfully managed with active intravascular rewarming. The patient was involved in a road traffic accident and was transported to a hospital. He was diagnosed with massive right-sided hemothorax, blunt aortic injury, burst fractures of the eighth and ninth thoracic vertebrae, and open fracture of the right tibia. He was referred to our hospital, where emergency surgery was performed to control bleeding from the right hemothorax. During surgery, the patient demonstrated progressive heat loss despite standard rewarming measures, and his temperature decreased to 32.4°C. Severe acidosis was also observed. A Cool Line® catheter was inserted into the right femoral vein and lodged in the inferior vena cava, and an intravascular balloon catheter system was utilized for aggressive rewarming. The automated target core temperature was set at 37°C, and the maximum flow rate was used. His core temperature reached 36.0°C after 125 min of intravascular rewarming. The severe acidosis was also resolved. The main active bleeding site was not identified, and coagulation hemostasis as well as rewarming enabled us to control bleeding from the vertebral bodies, lung parenchyma, and pleura. The total volume of intraoperative bleeding was 5,150 mL, and 20 units of red cell concentrate and 16 units of fresh frozen plasma were transfused. After surgery, he was transferred to the intensive care unit under endotracheal intubation and mechanical ventilation. His hemodynamic condition stabilized after surgery. The rewarming catheter was removed on day 2 of admission, and no bleeding, infection, or thrombosis associated with catheter placement was observed. Extubation was performed on day 40, and his subsequent clinical course was uneventful. He recovered well following rehabilitation and was discharged on day 46. These findings suggest that active intravascular rewarming should be considered as an aggressive, additional rewarming technique in patients with near-severe hypothermia associated with traumatic injury.

BACKGROUND:Heparin administration can induce the production of anti-platelet factor 4 (PF4)/heparin antibodies with platelet-activating properties, causing heparin-induced thrombocytopenia (HIT). Previous studies have suggested that trauma severity influences HIT immune responses, but their relationship has not been fully explained. This study aimed to clarify this association by multicenter prospective observational study. METHODS:Trauma patients who met the criteria of age 18 years or older and Injury Severity Scores (ISSs) of ≥9 from March 2018 to February 2019 were included. Patients who did not receive any heparin and those who received it as flushes or for treatment were also included. Patients were divided into three groups based on trauma severity (to mild , moderate , and severe injury groups [ISS ≥25]) and were compared by the seroconversion time and rate, as well as the disappearance rate of antibodies on day 30. RESULTS:A total of 184 patients were included: 55, 62, and 67 patients were classified into the mild, moderate, and severe injury groups, respectively. Overall, the seroconversion rates of anti-PF4/heparin immunoglobulin G (IgG) and HIT antibodies by washed platelet activation assay were 26.6% and 16.3%, respectively. There was a significant difference in the seroconversion rates of anti-PF4/ heparin IgG ( p = 0.016) and HIT antibodies ( p = 0.046) among the groups. Seroconversion rates in both assays increased with increasing trauma severity. The time required to achieve seroconversion was similar (between 5 and 10 days of trauma onset) regardless of heparin administration. Anti-PF4/heparin IgG and HIT antibodies were no longer detected on day 30 in 28.6% and 60.9% of seroconverted patients, respectively. CONCLUSION:Development of HIT antibodies was observed commonly in severely injured trauma patients. Heparin-induced thrombocytopenia antibody development may be related to trauma severity, with a high disappearance frequency on day 30.

BACKground: Heparin administration can induce the production of anti-platelet factor 4 (PF4)/heparin antibodies with platelet-activating properties, causing heparin-induced thrombocytopenia (HIT). Previous studies have suggested that trauma severity influences HIT immune responses, but their relationship has not been fully explained. This study aimed to clarify this association by multicenter prospective observational study.methods: Trauma patients who met the criteria of age ≥18 years and Injury Severity Scores (ISS) ≥ 9 from March 2018 to February 2019 were included. Patients who did not receive any heparin and those who received it as flushes or for treatment were also included. A total of 184 patients were divided into three groups based on trauma severity (mild (9 ≤ ISS ≤ 15), moderate (16 ≤ ISS ≤ 24), severe (25 ≤ ISS)), and were compared by the seroconversion time and rate, as well as the disappearance rate of antibodies on day 30. RESULTS: Overall, the seroconversion rates of anti-PF4/heparin IgG and HIT antibodies by washed platelet activation assay were 26.6% and 16.3%, respectively. There was a significant difference in the seroconversion rates of anti-PF4/heparin IgG (p = 0.016) and HIT antibodies (p = 0.046) among the groups. Seroconversion rates in both assays increased with increasing trauma severity. The time required to achieve seroconversion was similar (between 5 and 10 days of trauma onset) regardless of heparin administration. Anti-PF4/heparin IgG and HIT antibodies were no longer detected on day 30 in 28.6% and 60.9% of seroconverted patients, respectively.Conclusions: Development of HIT antibodies was observed commonly in severely injured trauma patients. HIT antibody development may related to trauma severity, with high disappearance rate on day 30. HIT should be considered as a differential diagnosis in patients with thrombocytopenia or thromboembolism between 5 and 10 days after trauma.