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
Factor ( F) VIIIactivity, 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 FVIIIand 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 (
RBCs) in 5% human albumin solution ( HAS), which reduced RBCs, 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, BECAmice were transfused with HAS, wild‐type murine fresh‐frozen plasma ( WT mFFP), or mFFPfrom FVIII−/− or Fg−/− knockout mice. BECAmice were also subjected to laser‐induced arteriolar injury and thrombus formation quantified by intravital microscopy. Results
WTor FVIII−/− mFFPreduced blood loss by fourfold in BECAmice relative to HAS; Fg−/− mFFPhad no effect. WTor FVIII−/− mFFPtransfusion, but not that of Fg−/− mFFP, increased thrombus size in laser‐injured BECAmice arterioles. Extended refrigerated storage of mFFPdid not reduce its antihemorrhagic effects. Conclusions
The content of
Fg, but not FVIII, determined the efficacy of plasma transfusion in coagulopathic mice.