Comparison of platelet-derived and plasma factor VIII efficacy using a novel native whole blood thrombin generation assay.

摘要: SummaryBackground We have recently developed a successful gene therapy approach for hemophilia A in which factor VIII (FVIII) expression is targeted to platelets by the αIIb promoter. Levels of platelet-expressed FVIII (2bF8) achieved may vary between individuals due differences ex vivo transduction and efficiency. Accurate assays evaluate 2bF8 efficacy are desirable. Objective To compare hemostatic with replacement over wide therapeutic dose range. Methods Efficacy was assessed using new transgenic mouse model expressing high levels (LV18tg). Blood from LV18tg mice or FVIIInull infused recombinant mixed blood at different ratios achieve several concentrations plasma FVIII. Samples were evaluated novel native whole thrombin generation assay that uses recalcified without addition tissue initiate coagulation. Results FVIII dependency observed all five parameters. While total amount generated similar, significantly accelerated compared Remarkably, 10-fold lower than (0.2% vs. 2%) shortened onset peak blood. Conclusion Using model, we showed established here can be used monitor platelet therapy. The higher seemed acceleration generation.