High-dose Factor XIII administration induces effective hemostasis for trauma-associated coagulopathy (TAC) both in vitro and in rat hemorrhagic shock in vivo models

Abstract

Human in vitro and rat in vivo experimental study.

Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study

“…The use of albumin for hemodilution might explain these opposing results, because albumin is known to impair coagulation to a higher degree than other colloids [ 15 , 36 ]. In summary, these findings support the hypothesis that during massive transfusion, next to fibrinogen, an ultra-high dosage of FXIII is needed for the effective therapy of dilutional coagulopathy [ 22 , 23 , 34 ].…”

“…This observational study was performed in order to identify the potential benefit of a combined fibrinogen/FXIII therapy for the treatment of dilutional coagulopathy by the use of an in-vitro massive transfusion model. In contrast to previous studies, this investigation was based on reconstituted blood in order to simulate massive transfusion rather than to dilute the blood of healthy donors [ 16 , 17 , 22 , 23 , 24 , 25 ]. The study was able to show the negative effect of hemodilution by identifying alterations of the thrombelastography, which were unsurprisingly more severe in the samples diluted by 40%.…”

“…For this reason, we assumed that a dosage of 75 IU/kg should be sufficient for the treatment of FXIII deficiency in patients suffering from a major hemorrhage. The varying success rate of FXIII therapy might be explainable by the study of Nagashima et al, which showed that only ultra-high dosages of FXIII were able to improve clot firmness in an in-vitro hyperfibrinolysis model [ 23 ]. However, this study did not include the substitution of fibrinogen, which might be a reason why lower FXIII dosages did not result in improvement of MCF.…”

“…The result was independent of the degree of dilution. Previous studies suggest that ultra-high dosages of FXIII might be necessary for improved clot stability [ 22 , 23 , 34 ]. However, these studies used healthy blood samples, which are hardly representative of major hemorrhage.…”

Bad blood: A coagulopathy associated with trauma and massive transfusion review

“…Currently, this is not standard treatment, but other groups have found better results in combining them with FFP than FFP alone . A recent intriguing study from Japan also noted a therapeutic effect of high‐dose factor XIII in a human in vitro and rat in vivo model …”