Blood Journal

RESULTS

A. Effects of recombinant Factor 8 (rFVIII) on Rotation Thromboelastometry (ROTEM) Parameters

The addition of recombinant Factor 8 in vitro to the whole blood of two patients positive for Type 3 Von Willebrand Disease significantly reduced the Clotting time and Clot-Formation Time. These thromboelastometric changes are dose dependent and clinically significant. The in vitro results indicated that the addition of rFVIII supported procoagulant activity.

Intravenous administration of rFVIII in both patients with type 3 VWD also significantly decreased the CT and CFT and increased the velocity of clot formation. The Maximum clot firmness decreased but the change was not statistically significant.

B. Effects of rFVIII on Agonist-Induced Platelet Aggregation in PRP

The type 3 VWD native PRP responded well to collagen and was slightly affected by the addition of rFVIII. In thrombin-induced aggregation in vitro, however, a weak response was seen in native PRP, and this response was enhanced by rFVIII addition. When the weakly responding native PRP is given a final rFVIII concentration of 2.0 U/mL, this will mediate maximum aggregation. On the other hand, the addition of ristocetin to patient’s platelets with type 3 VWD mediated a slight response both before and after the addition of rFVIII.

Recombinant Factor 8 replacement potentiated thrombin-induced platelet aggregation to an extent comparable with normal aggregation but did not improve ristocetin-induced platelet aggregation.

C. Effects of rFVIII on Shear-Induced Platelet Aggregation (SIPA)

In vitro addition of rFVIII to type 3 VWD PRP had little effect on curves of shear-induced aggregation. Almost no aggregation was seen under high-shear conditions, and only slight aggregation was observed under low-shear conditions, both in the presence and absence of rFVIII.

Intravenous Infusion of rFVIII, improved the significant aggregation induced by low shear, whereas minute platelet...