Hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion: a retrospective observational multicentre study

Abstract

BackgroundHyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/fibrinogen degradation product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI.MethodsWe conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score ≥ 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head ≥ 4 and an extra-cranial AIS < 2. The non-TBI group included patients with an extra-cranial AIS ≥ 3 and head AIS < 2. Hyperfibrinolysis was defined as a D-dimer level ≥ 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients.ResultsWe enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group.ConclusionsHyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1811-1) contains supplementary material, which is available to authorized users.

Probability of Soluble Tissue Factor Release Lead to the Elevation of D-dimer as a Biomarker for Traumatic Brain Injury

“…There are three major hypotheses for the mechanism of coagulopathy after trauma: that massive transfusion and infusion in initial treatment after trauma dilute the blood, resulting in a shortage of blood coagulation factors; 11,12) that hypotension induces protein C activation, which activates fibrinolysis; 13) and that tissue factors are released from TBI-damaged brain tissues into the blood, and the coagulation cascade is then activated by these factors. 14) We have shown a relationship of brain injury with D-dimer levels in mild isolated TBI in previous studies, 7,8) and patients without blood dilution due to massive transfusion and infusion or hypotension during treatment still have abnormalities in the coagulation and fibrinolytic system 21) that are not associated with the mechanism of coagulation disorder after TBI. The results of this study suggest that sTF is involved in the mechanism of coagulopathy after TBI.…”

Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis

“…Furthermore, on sub-group analysis of patients with severe brain injury, although there were no significant differences, we observed that early FC administration tended to improve the survival rate of the patients. In patients with severe brain injury, hyperfibrinolysis is frequently observed at admission to the ED [43,44]; this contributes to enlargement of intracranial haematomas, trauma-induced coagulopathy, and poor outcomes [43,[45][46][47]. In this context, FC may help restore haemostasis by complementing plasma fibrinogen, which deteriorates owing to hyperfibrinolysis in patients with severe brain injury.…”

Restrictive transfusion strategy for critically injured patients (RESTRIC) trial: a study protocol for a cluster-randomised, crossover non-inferiority trial

“…TRALI is defined according to the Toronto definition, 17 and sepsis is defined according to sepsis-3. 18 Sample size In our previous retrospective multicentre observational study, wherein data were collected from 796 patients with severe trauma from 15 hospitals during a 1-year period, [19][20][21][22][23][24][25][26] 241 patients received RBC concentrates during the first 24 hours after arrival at the ED and 25% of the patients transfused with RBC concentrates died within 28 days after arrival at the ED. Based on these results, we assumed a mortality rate of 25% at 28 days after arrival in the ED among patients receiving a liberal RBC transfusion strategy.…”