Early administration of fibrinogen concentrate in severe trauma patients

Does early administration of fibrinogen concentrate improve the survival of severe trauma patients?

Itagaki Y, Hayakawa M, Maekawa K, Saito T, Kodate A, Honma Y et al. Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis. World J Emerg Surg. 2020;15:7. doi:10.1186/s13017-020-0291-9.

Uncontrolled bleeding during the early phases of major trauma remains a primary cause of death (Kauvar et al., 2005; Naghavi et al., 2017). Fibrinogen plays an important role in regulating haemostasis and clot formation during trauma, and is one of the first coagulants to fall to critically low levels, which is associated with poor outcomes (Sawamura et al., 2009; Rourke et al., 2012; Hayakawa et al., 2015; Nakamura et al., 2017). Several reports indicate that treatment with fibrinogen concentrate may improve outcome for patients with severe trauma; however, possible differences related to the timing of fibrinogen concentrate administration remain to be addressed (Schöchl et al., 2010; Wafaisade et al., 2013; Innerhofer et al., 2017; Akbari et al., 2018).

In this single-centre, retrospective study, Itagaki and colleagues used propensity score-matching (n = 31 matched pairs) to show that fibrinogen concentrate administration within 1 hour of emergency department admission is associated with a favourable survival outcome in severe trauma patients (Figure 1).

Figure 1: Study design, in-hospital survival rate for severe trauma patients treated with early fibrinogen concentrate, and number of patients requiring transfusion. *p<0.05. FC, fibrinogen concentrate; FFP, fresh frozen plasma; PC, platelet concentrate; RBC, red blood cell.

The study included adult severe trauma patients (≥18 years and injury severity score ≥16) who did or did not receive fibrinogen concentrate within 1 hour of arrival to the emergency department. Propensity score-matching identified 31 patient pairs and was based on the trauma and injury severity score (TRISS), heart rate at emergency department admission, and age (c-statistic of 0.734). Patients who received early fibrinogen concentrate (median dose not reported) had a higher in-hospital survival rate compared to those who did not (log rank p=0.013), and a lower 28-day in-hospital mortality rate (19.3% versus 45%, p=0.03). It is important to point out that 61.2% of patients (19/31) who did not receive fibrinogen concentrate within the first hour ultimately received fibrinogen concentrate within the next 23 hours. However, this delayed administration of fibrinogen concentrate was not associated with the same improvement in severe trauma outcomes.

Interestingly, the fibrinogen group received significantly more red blood cells and fresh frozen plasma within the first 6 hours of admission to the emergency department. In this retrospective study, the decision to administer fibrinogen concentrate was made at the discretion of the attending physician, and most imbalanced variables were more severe in the fibrinogen concentrate group. This may explain the differences in transfusion volumes between the two groups. Other limitations to the study include small patient numbers and its single-centre retrospective study design.

This study suggests that early fibrinogen administration, within 1 hour of emergency department admission, may improve survival outcome for severe trauma patients; however, a larger randomised controlled trial is needed to confirm this.

Visit our learning zone section on the key clinical data for fibrinogen concentrate in treating patients who experience excessive bleeding during severe trauma.

References

Akbari E, Safari S, Hatamabadi H. The effect of fibrinogen concentrate and fresh frozen plasma on the outcome of patients with acute traumatic coagulopathy: a quasi-experimental study. Am J Emerg Med. 2018;36:1947–50.

Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A. Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study. Semin Thromb Hemost. 2015;41:35–42.

Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T et al. Reversal of traumainduced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017;4:e258–e271.

Kauvar DS, Wade CE. The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. Crit Care. 2005;9(Suppl 5):S1–9.

Naghavi M, Abajobir AA, Abbafati C, Abbas KM, Abd-Allah F, Abera SF et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1151–210.

Nakamura Y, Ishikura H, Kushimoto S, Kiyomi F, Kato H, Sasaki J et al. Fibrinogen level on admission is a predictor for massive transfusion in patients with severe blunt trauma: analyses of a retrospective multicentre observational study. Injury. 2017;48:674–9.

Rourke C, Curry N, Khan S, Taylor R, Raza I, Davenport R et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10:1342–51.

Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res. 2009;124:608–13.

Schöchl H, Forster L, Woidke R, Solomon C, Voelckel W. Use of rotation thromboelastometry (ROTEM) to achieve successful treatment of polytrauma with fibrinogen concentrate and prothrombin complex concentrate. Anaesthesia. 2010;65:199–203.

Wafaisade A, Lefering R, Maegele M, Brockamp T, Mutschler M, Lendemans S et al. Trauma Registry of DGU: Administration of fibrinogen concentrate in exsanguinating trauma patients is associated with improved survival at 6hours but not at discharge. J Trauma Acute Care Surg. 2013;74:387–3; discussion 393–385.