Abstract
The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3–7.8) mm; 20% dilution fibrinogen: 13.5 (13–17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3–18.8) mm; 40% dilution: 3 (2–3.8) mm; 40% dilution fibrinogen: 8 (7–11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3–11.8) mm; all p < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.
Highlights
Severe hemorrhage following major trauma represents a common cause of death and continues to be associated with high mortality [1,2]
Since the clot of mm strength (CFT), contrary to the CT, is highly dependent on sufficient platelet aggregation, these results indicate that hemodilution might have affected the concentration of platelets and their function [21,32]
It has to be emphasized that factor XIII (FXIII) activity was within the normal range prior to the beginning of the experiments indicating that the lacking therapeutic effect of combined fibrinogen/FXIII
Summary
Severe hemorrhage following major trauma represents a common cause of death and continues to be associated with high mortality [1,2]. Even though the treatment of trauma-induced coagulopathy (TIC) can be started at the site of the incident, the sole presence of TIC correlates with an increase in mortality [1,6,7,8,9]. This is caused by the complex pathophysiological reactions that are connected to TIC [9,10]. The disbalance of increased levels of tissue plasminogen activator (t-PA) and simultaneous reduction of plasminogen activator-inhibitor 1 (PAI-1) displays the driving force of hyperfibrinolysis, which concludes into a disseminated intravascular coagulopathy (DIC)
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