The fibrinogen but not the F actor VIII content of transfused plasma determines its effectiveness at reducing bleeding in coagulopathic mice

Background The evidence supporting plasma transfusion as a means to restore hemostatic control and prevent or treat bleeding is weak, leading to uncertainties as to which proteins affect the therapeutic quality of plasma. Some regulators focus on coagulation F actor ( F ) VIII activity, but whether this measure reflects overall transfusable plasma efficacy is questionable. We developed a mouse model of coagulopathy in which bleeding outcomes were responsive to plasma transfusion and addressed the relative contributions of FVIII and fibrinogen ( Fg ) to plasma quality. Study Design and Methods Anesthetized mice were rendered coagulopathic by four rounds of exchange of whole blood for washed red blood cells ( RBC s) in 5% human albumin solution ( HAS ), which reduced RBC s, platelets, and plasma protein levels by 55, 66, and 80% of starting levels, in a blood exchange‐induced coagulopathy approach ( BECA ). Before tail vein transection, BECA mice were transfused with HAS , wild‐type murine fresh‐frozen plasma ( WT mFFP ), or mFFP from FVIII −/− or Fg −/− knockout mice. BECA mice were also subjected to laser‐induced arteriolar injury and thrombus formation quantified by intravital microscopy. Results Transfusion of WT or FVIII −/− mFFP reduced blood loss by fourfold in BECA mice relative to HAS ; Fg −/− mFFP had no effect. WT or FVIII −/− mFFP transfusion, but not that of Fg −/− mFFP , increased thrombus size in laser‐injured BECA mice arterioles. Extended refrigerated storage of mFFP did not reduce its antihemorrhagic effects. Conclusions The content of Fg , but not FVIII , determined the efficacy of plasma transfusion in coagulopathic mice.