The efficacy of coagulation factor concentrates in the management of patients with trauma- induced coagulopathy: a systematic review and meta-analysis
Authors: Itagaki Yuki , Hayakawa Mineji , Takahashi Yuki , Kushimoto Shigeki , Sakamoto Yuichiro , Seki Yoshinobu , Okamoto Kohji 
Published: January 2024

Abstract
Introduction: Uncontrolled bleeding during the early phase of trauma is primarily attributable to death, which is exacerbated by Trauma-induced coagulopathy (TIC). Several randomized controlled trials (RCTs) have investigated interventions of supplementation for transfusion, coagulation factors, and tranexamic acid for hemostasis of trauma. Although several systematic reviews and meta-analyses have been conducted, no systematic review and meta-analysis has focused on the TIC. Therefore, a comprehensive synthesis of the available evidence on interventions for TIC is needed.
Methods and analysis: We conducted a systematic review and meta-analysis of blood component products and tranexamic acid administrations for severe trauma patients with TIC. TIC was defined as abnormalities of coagulo-fibrinolytic laboratory markers or clinically evident bleeding tendency during the resuscitation phase. We included randomized controlled trials and non-randomized controlled trials. The study population included in this review was patients who required transfusion with any coagulopathy associated with trauma and a detailed definition in each included study. The intervention was the administration of blood component products and tranexamic acid. The control group was administered with ordinal transfusion or placebo. The primary outcome of the study is mortality due to all causes and the quantity of the transfusion. We searched electronic databases such as MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Two reviewers independently screened the title and abstract, retrieved the full text of the selected articles, and extracted the essential data. We applied uniform criteria for evaluating the risk of bias associated with individual RCTs and non-randomized trials based on the Cochrane risk of bias tool. Values of the risk ratio were expressed as a point estimate with 95% confidence intervals (CIs). Data of continuous variables were expressed as the mean difference along with their 95% CIs and P values. We assessed the strength of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
Results: Four RCTs and seven observational studies were included in the qualitative synthesis. Fibrinogen concentrate (FC) administrations may reduce mortality with very low certainty of evidence. Prothrombin coagulation cofactors (PCC) administrations may result in a large reduction in in-hospital mortality with low certainty of evidence. Combination administrations of FC and PCC (FC + PCC) probably result in an increase in mortality with moderate certainty of evidence. Recombinant activated factor VII (rFⅦa) administrations may have increased in-hospital mortality with very low certainty of evidence. FC administrations may reduce amounts of red blood cell (RBC) transfusion with very low certainty of evidence. PCC administrations result in a large reduction of RBC transfusion. FC + PCC administrations result in a large reduction in RBC with high certainty of evidence. FC and FC + PCC administrations tend to reduce multiple organ failure with very low to moderate certainty of this evidence.
Conclusions:
The present study indicates that FC and/or PCC administrations tend to reduce mortality and transfusion amounts in patients with coagulopathy-associated trauma. Furthermore, complications were reduced by FC and PCC administration. As our systematic review and metanalysis did not reveal high certainty of evidence, blood component products, such as FC and PCC supplementation for TIC should be investigated in more well-constructed trials.
This study protocol has been funded through a protocol registry. The registry number is UMIN000050170, Registered 29 January 2023.