The effect of fibrinogen and prothrombin complex concentrate on dilutional coagulopathy in a porcine model of uncontrolled hemorrhagic shock

Purpose

Dilutional coagulopathy is a common complication in severely injured patients and a consequence of blood loss, administration of synthetic colloids and red blood cell concentrates to compensate huge blood losses. This study was conducted to assess whether substituting the combination of fibrinogen and pro-thrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy, and whether this treatment leads to a reduction in further blood loss and mortality.

Methods

Anesthetized pigs (n = 20) were instrumented for blood sampling and hemodynamic monitoring. About 66% of the calculated blood volume was withdrawn and replaced with hydroxyethylstarch (130 HES 0.4). Then, pigs were randomized to receive either 200 mg/kg fibrinogen and 35 IE/kg PCC (n = 10) or placebo (n = 10). Thereafter, a standard liver laceration was performed to induce uncontrolled hemorrhage. Modified thrombelastography was used to assess the dynamics and quality of clot formation.

Results

After hemodilution both groups showed statistically significant increased clotting times (CT), clot formation times (CFT), and decreased maximum clot firmnesses (MCF). After fibrinogen and PCC administration, CT and CFT decreased whereas MCF increased statistically significantly. Median blood loss after liver injury was significantly smaller in the animals treated with clotting factor concentrates versus the placebo group: 240.0 ml (50.0–830.0) vs 1.800 ml (1.500–2.500) (P < 0.0001). All animals, treated with fibrinogen and PCC survived, whereas 80% of the placebo group died after liver laceration (P < 0.0001).

Conclusion

During hemodilution, substitution of fibrinogen and PCC leads to an enhancement in coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolemia during huge blood losses.