Comparison between two concentrates with factor VIII inhibitor bypassing activity

Area of Science:

• Biochemistry
• Hematology
• Pharmacology

Background:

• Activated prothrombin complex concentrates (aPCCs) are used to treat bleeding disorders.
• Feiba and Autoplex are two commonly used aPCCs.
• Understanding their comparative clotting activities and thrombogenicity is crucial for clinical application.

Purpose of the Study:

• To compare the clotting activities and thrombogenicity of Feiba and Autoplex in a rabbit model.
• To elucidate the specific factor differences contributing to potential variations in hemostatic efficacy and safety.

Main Methods:

• In vitro assays were used to measure clotting factor concentrations, including factor VII, activated serine proteases (VIIa, IXa), and factors Xa and IIa.
• The influence of calcium chloride, factor VIII, phospholipid, and antithrombin III on clotting factor activity was assessed.
• In vivo thrombogenicity was evaluated in rabbits using the Wessler test.

Main Results:

• Autoplex exhibited higher concentrations of factor VII, VIIa, and IXa compared to Feiba.
• Both concentrates generated low levels of Xa and IIa upon calcium chloride incubation, with a more pronounced increase in Autoplex when factor VIII and phospholipid were added.
• Antithrombin III rapidly diminished Xa and IIa activities, but Factor IXa clearance was slower from Autoplex.
• Thrombogenicity in rabbits was significantly higher for Autoplex than for Feiba, with an average factor of 12.8–17.8.

Conclusions:

• Autoplex possesses higher prothrombinase activities and exhibits significantly greater thrombogenicity in rabbits compared to Feiba.
• These findings highlight important differences in the hemostatic potential and potential risks associated with these two aPCCs.
• Further clinical studies are warranted to correlate these preclinical findings with patient outcomes.