In vitro comparative study of hemostatic components in warfarin-treated and fibrinogen-deficient plasma

Objective: The authors hypothesized that various hemostatic products may differently affect viscoelastic clot formation depending on their respective procoagulant activity and fibrinogen content.

Design: In vitro coagulopathy modeling using warfarin-treated plasma (international normalized ratio, 2.8-3.8) and fibrinogen-deficient plasma evaluated by rotational thromboelastometry (ROTEM; Pentapharm, Munich, Germany).

Setting: A university laboratory.

Intervention: Different volumes of cryoprecipitate, fresh frozen plasma (FFP), fibrinogen concentrate, and platelet concentrate were mixed with each abnormal plasma to simulate the in vivo transfusions of 250 mL to 1,000 mL. Three thromboelastometric variables that reflect the rate and extent of clot growth were measured: (1) coagulation time (CT), (2) angle, and (3) maximal clot firmness (MCF).

Measurements and main results: In warfarin-treated plasma, the addition of FFP, cryoprecipitate, and platelets led to a dose-dependent improvement of CT and angle, whereas MCF increased with cryoprecipitate or platelets only. The addition of fibrinogen concentrate improved MCF and angle but not CT. In fibrinogen-deficient plasma, the addition of cryoprecipitate, platelets, and fibrinogen concentrate led to a dose-dependent improvement of ROTEM variables, whereas the addition of FFP resulted in significantly longer CT and lower MCF values compared with other hemostatic products. The addition of platelets in the presence of cytochalasin D (a platelet inhibitor) resulted in improvements of ROTEM variables that were similar to when FFP was added to warfarin-treated and fibrinogen-deficient plasma.

Conclusions: Cryoprecipitate supports clot formation on ROTEM more efficiently than FFP because of the high fibrinogen content. Improved ROTEM variables after platelet addition are presumably caused by increased interaction among thrombin-activated platelets and fibrinogen.