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Background: Coagulopathic bleeding is frequently present after major trauma. However, trauma-induced coagulopathy (TIC) remains incompletely understood. This laboratory analysis of blood samples derived from our completed trial on fibrinogen in the initial resuscitation of severe trauma (FiiRST) was conducted to evaluate TIC and associated responses to fibrinogen replacement.Study Design and Methods: We conducted a retrospective evaluation of TIC in 45 FiiRST trial patients based on rotational thromboelastometry (ROTEM), international normalized ratio (INR), and biomarkers for hemostasis and endotheliopathy. Whole blood was analyzed by ROTEM. Plasma was analyzed for INR and biomarkers.Results: Overall, 19.0% and 30.0% of the FiiRST trial patients were coagulopathic on admission defined by EXTEM maximum clot firmness out of the range of 40-71 mm and INR >1.2, respectively. The FiiRST patients showed lower fibrinogen, factor II and V levels, protein C and antiplasmin activities, higher activated protein C, tissue plasminogen activator, d-dimer, and thrombomodulin concentrations at admission than healthy controls. Most of the biomarkers changed their activities during 48-h hospitalization, but were at abnormal levels even 48-h after admission. The fibrinogen treatment reduced hypofibrinogenemia and increased factor XIII level, but had no significant effects on other biomarkers levels. Limited development of endotheliopathy was indicated by syndean-1, thrombomodulin, and sE-selectin.Conclusions: About 19%-30% of the trauma patients in the FiiRST trial were coagulopathic on hospital admission depending on the definition of TIC. Analyses of the TIC biomarkers demonstrated that hemostasis would not return to normal after 48-h hospitalization, and fibrinogen replacement improved hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

Introduction: Canadian Armed Forces adopted fibrinogen concentrate (RiaSTAP) for hemostatic resuscitation in the far-forward combat setting, given its potential benefits of reducing blood loss, blood transfusion and mortality, and its long storage stability and high portability. The current guidance recommends that RiaSTAP should be administered within 8 hours after reconstitution when stored at room temperature. However, little information about its stability is available. There is also a need to investigate the stability and efficacy of RiaSTAP after reconstitution and exposure to extreme temperatures in which our forces may operate.Materials and Methods: RiaSTAP was reconstituted as per manufacturer's instruction and stored at specific temperatures (-20°C, 4°C, 22°C, 35°C, 42°C, or 50°C) for up to 6 months. Reconstituted RiaSTAP was also oscillated on a rocker at 18 rpm under 22°C and 50°C. Its hemostatic function was measured using rotational thromboelastometry performed with RiaSTAP-spiked whole blood. Fibrinogen concentrations were measured by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Gel electrophoresis was also conducted for initial and stored samples.Results: We found no change to the hemostatic function of reconstituted RiaSTAP after storage at -20°C for 6 months. At 4°C, no obvious changes to the hemostatic effect of reconstituted RiaSTAP relative to 0 hours were seen until 1,680 hours. At 22°C, a remarkable decrease began after storage for 168 hours. Storage at 35°C significantly decreased the hemostatic effect after 144 hours, while the storage at 42°C resulted in decreased hemostatic function after 72 hours. Finally, storage at 50°C for 8 hours resulted in complete loss of hemostatic function. Compared to the hemostatic activity, the fibrinogen concentration for reconstituted RiaSTAP showed less change over time. No apparent decline in fibrinogen concentration was seen after storage at -20°C for 6 months and at 4°C for 1,680 hours. At 22°C, there were no clear alterations until 792 hours. There was a decline in fibrinogen concentration at 35°C and 42°C after 672 and 600 hours of storage, respectively. At 50°C, little amount of fibrinogen was detected by ELISA at 8 hours. Similar changes in the hemostatic effect and fibrinogen concentration over time were observed under the rocking condition in comparison with the static condition at the same temperature. The gel electrophoresis confirmed fibrinogen degradation which increased with storage temperature and time.Conclusions: The stability of reconstituted RiaSTAP decreases with increasing storage temperature. The hemostatic function deteriorated before fibrinogen concentration and integrity were significantly altered at all temperatures for the study period except at 50°C where there was a rapid decline in both hemostatic function and fibrinogen concentration. Sample oscillation did not significantly affect its stability. The shelf life of reconstituted RiaSTAP may, therefore, be recommended accordingly when stored at different temperatures and extended to 6 days at room temperature provided that sterility is maintained. [ABSTRACT FROM AUTHOR]

Both thrombelastography (TEG) and rotational thromboelastometry (ROTEM) have been investigated for diagnosis of coagulopathy and guidance of resuscitation in trauma and surgery. Given similarities between the two systems, it is important to determine whether one is superior to the other and how comparable they are to conventional coagulation tests (CCTs). Therefore, we conducted a comparative study of functional fibrinogen and coagulation assays using TEG and ROTEM and CCTs to determine their capability to monitor coagulation profiles, diagnose coagulopathy and predict blood transfusion requirements in trauma patients. Blood samples were collected from 45 patients at admission and during 48-h hospitalization as part of a randomized control trial on early fibrinogen replacement in trauma. Functional fibrinogen (FF) TEG, ROTEM FIBTEM and EXTEM, and CCTs were performed and compared. We found significant differences between the placebo and fibrinogen groups over hospitalization time in FF TEG MA, ROTEM CT, MCF and LI30. FF TEG MA and ROTEM FIBTEM MCF mirrored plasma fibrinogen profiles, reached a maximum difference between the two groups 1–3 h after fibrinogen administration. In comparison, CCTs detected minimal hemostatic changes by fibrinogen treatment. TEG and ROTEM showed various degrees of correlations with CCTs. TEG MA and ROTEM MCF provided better predictions for plasma and RBC transfusions than CCTs, but poor accuracy for cryoprecipitate transfusion. Both TEG and ROTEM well predicted hypofibrinogenemia (fibrinogen concentration < 1 g/L), but poorly detected coagulopathy (INR ≥ 1.2). TEG and ROTEM detected increases in clot strength following early use of fibrinogen. ROTEM also detected changes in coagulation time and clot lysis. Both were better than CCTs for monitoring coagulation profiles and predicting transfusion requirements. • TEG and ROTEM play an important role in monitoring and guiding transfusion decisions in trauma. • TEG and ROTEM fibrinogen assays were compared with conventional coagulation tests (CCTs) in trauma patients. • TEG and ROTEM were superior to INR and PTT to detect the effects of fibrinogen replacement on hemostasis. • ROTEM FIBTEM detected more changes in parameters than functional fibrinogen TEG. • TEG and ROTEM fibrinogen assays provided better predictions for RBC and plasma transfusions than CCTs. [ABSTRACT FROM AUTHOR]

Fibrinogen is crucial for the formation of blood clot and clinical outcomes in major bleeding. Both Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) have been increasingly used to diagnose fibrinogen deficiency and guide fibrinogen transfusion in trauma and surgical bleeding patients. We conducted a comprehensive and comparative review on the technologies and clinical applications of two typical functional fibrinogen assays using TEG (FF TEG) and ROTEM (FIBTEM) for assessment of fibrinogen level and deficiency, and prediction of transfusion requirement. Clot strength and firmness of FF TEG and ROTEM FIBTEM were the most used parameters, and their associations with fibrinogen levels as measured by Clauss method ranged from 0 to 0.9 for FF TEG and 0.27 to 0.94 for FIBTEM. A comparison of the interchangeability and clinical performance of the functional fibrinogen assays using the two systems showed that the results were correlated, but are not interchangeable between the two systems. It appears that ROTEM FIBTEM showed better associations with the Clauss method and more clinical use for monitoring fibrinogen deficiency and predicting transfusion requirements including fibrinogen replacement than FF TEG. TEG and ROTEM functional fibrinogen tests play important roles in the diagnosis of fibrinogen-related coagulopathy and guidance of transfusion requirements. Despite the fact that high-quality evidence is still needed, the two systems are likely to remain popular for the hemostatic management of bleeding patients. [ABSTRACT FROM AUTHOR]

Background:The impact of combining plasma fibrinogen levels with Epstein-Barr Virus DNA (EBV DNA) levels on the prognosis for patients with nasopharyngeal carcinoma (NPC) was evaluated.Methods:In this observational study, 2563 patients with non-metastatic NPC were evaluated for the effects of circulating plasma fibrinogen and EBV DNA levels on disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS).Results:Compared with the bottom biomarker tertiles, TNM stage-adjusted hazard ratios (HR, 95% confidence intervals (CIs)) for predicting DFS in fibrinogen tertiles 2 to 3 were 1.26 (1.00 to 1.60) and 1.81 (1.45 to 2.26), respectively; HR for EBV DNA tertiles 2 to 3 were 1.49 (1.12 to 1.98) and 4.24 (3.27 to 5.49), respectively. After additional adjustment for established risk factors, both biomarkers were still associated (P for trend <0.001) with reduced DFS (HR: 1.79, 95% CI, 1.43 to 2.25 for top fibrinogen tertiles; HR: 4.04, 95% CI: 3.10 to 5.27 for top EBV DNA tertiles compared with the bottom tertiles). For patients with advanced-stage disease, those with high fibrinogen levels (⩾3.34 g l−1) presented with worse DFS, regardless of EBV DNA ⩾4000 or <4000 copies ml−1 subgroup. Similar findings were observed for DMFS and OS.Conclusions:Circulating fibrinogen and EBV DNA significantly correlate with NPC patients survival. Combined fibrinogen and EBV DNA data lead to improved prognostic prediction in advanced-stage disease. [ABSTRACT FROM AUTHOR]