Defining a fibrinogen-to-factor XIII replacement ratio in an in-vitro model of dilutional coagulopathy

Massive blood loss during surgery or trauma leads to dilutional coagulopathy. While fibrinogen is typically the first factor to reach critical levels, factor XIII (FXIII) also decreases proportionally, further impairing clot stability. Routine coagulation tests are insensitive to FXIII, leading to unrecognised deficiency during acute bleeding. This study aimed to define an optimal fibrinogen-to-FXIII replacement ratio to empirically restore adequate haemostasis.

In an in-vitro haemodilution model using blood from 20 healthy volunteers, we simulated a 70% loss of circulating blood volume. Five incremental combinations of fibrinogen (0-200 mg/kg) and FXIII (0-50 IU/kg) were tested. Coagulation status was analyzed via standard laboratory parameters, viscoelastic testing and confocal microscopy.

Haemodilution reduced fibrinogen from a median of 294 to 73 mg/dL and FXIII activity from a median of 130 to 31%. Fibrinogen monotherapy at 50 mg/kg restored fibrinogen target levels (≥ 150 mg/dL) but failed to reach FXIII targets (>60%). The lowest combination of fibrinogen and FXIII to achieve both therapeutic goals was 50 mg/kg and 25 IU/kg, respectively. FXIII demonstrated a strong synergistic effect on clot firmness (FIBtest MCF); when combined with 25 IU/kg FXIII, half the fibrinogen dose was needed to reach functional thresholds. Confocal imaging showed best interconnected fibrin networks with combined therapy.

Our data indicate that a fibrinogen-to-FXIII replacement ratio of approximately 2:1 (mg/kg to IU/kg) effectively restores clot stability in dilutional coagulopathy. This ratio may provide a practical framework for empirical therapy when rapid FXIII assessment is unavailable.