Correlation between factor (F)XIa, FIXa and tissue factor and trauma severity

Abstract

BACKGROUND It has been observed that trauma patients often display elevated procoagulant activity that could be caused, in part, by tissue factor (TF). We previously observed that trauma patients with thermal, blunt and penetrating injuries have active FIXa and FXIa in their plasma. In the current study we evaluated the effect of injury severity, with or without accompanying shock, on the frequency and concentration of TF, FIXa and FXIa in plasma from trauma patients. METHODS Eighty trauma patients were enrolled and divided equally into 4 groups based on their injury severity score (ISS) and base deficit (BD): Group 1: Non-severe injury, no shock Group 2: Non-severe injury, with shock Group 3: Severe injury, no shock Group 4: Severe injury, with shock Blood was collected at a 0 time-point (first blood draw upon arrival at hospital) and citrate plasma was prepared, frozen and stored at −80C. FXIa, FIXa and TF activity assays were based on a response of thrombin generation to corresponding monoclonal inhibitory antibodies. RESULTS The frequency and median concentrations of TF were relatively low in non-severe injury groups (17.5 % and 0 pM respectively) but were higher in those with severe injury (65% and 0.5 pM, respectively). While FXIa was observed in 91% of samples and was high across all 4 groups, median concentrations were highest (by approximately 4-fold) in groups with shock. FIXa was observed in 80% of plasma samples and concentrations varied in a relatively narrow range between all 4 groups. No endogenous activity was observed in plasma from healthy individuals. CONCLUSIONS 1) Frequency and concentration of TF is higher in patients with a higher trauma severity; 2) Concentration of FXIa is higher in patients with shock; 3) For the first time reported, the vast majority of plasma samples from trauma patients contain active FIXa and FXIa. LEVEL of EVIDENCE Diagnostic Tests or Criteria, level I. Diagnostic Tests.

Endogenous Procoagulant Activity in Trauma Patients and Its Relationship to Trauma Severity

“…Indeed, we observed in a previous study that the majority of trauma patients have both TF and FXIa present in plasma. 15 Similar results related to FXIa and TF activity were also obtained for patients with inflammatory bowel disease 16 and various cardiovascular diseases, 17 18 19 especially those with acute coronary syndrome, which have active FXIa in their plasma for which the concentrations correlates with markers of inflammation and thrombin generation. 17 A significant fraction of those patients also had detectable TF activity, which, most likely, could be assigned to TF presented on microparticles.…”

Continuous thrombin generation in whole blood: New applications for assessing activators and inhibitors of coagulation

“…In several previously published studies we observed an endogenous procoagulant activity present in plasma of cardiovascular and trauma patients and in plasma of patients with inflammatory diseases (10, 18, 33–35). This activity is caused by the presence of either functional TF or active FXIa or FIXa, or by any combination of these 3 proteins.…”

“…CTI, an inhibitor of FXIIa (20), efficiently prevents thrombin generation in PCPS-containing plasma from healthy individuals in the absence of TF (10) because TG is triggered by the contact pathway. Based on the previously published data (16) and on the data of this study, CTI inhibits thrombin generation in whole blood as well.…”

“…This experiment is a modification of previously published assays in plasma (10) and is based on the response of the lag phase of thrombin generation in CTI-treated fresh whole blood to the addition of inhibitory monoclonal antibodies to FXIa, FIXa and TF. Blood was collected from a trauma patient at the University of Vermont Medical Center (UVMMC) into 3.2% sodium citrate, CTI was added to collected blood to achieve 0.1 mg/mL and the blood was kept at room temp.…”

“…In addition to these functions, thrombin increases clot stability by activating factor XIII and thrombin activatable fibrinolysis inhibitor. So, it is not surprising that a decreased thrombin potential correlates with bleeding tendencies (hemophilia) (5, 7) and an elevated potential correlates with a prothrombotic phenotype related to cardiovascular diseases (8, 9), trauma-induced coagulopathy (10), cancer (11), etc . To better evaluate hemostatic potential, new tests measuring thrombin generation in native or “synthetic” plasma were developed (12, 13).…”