Procoagulant Microparticle Interactions Due to P-sel-Ig in Hemophilia A Patients

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Congenital hemophilia is a hereditary, X-linked blood-clotting disease that involves insufficient clotting factors VIII and IX. There are two types of hemophilia, Hemophilia A and Hemophilia B. Hemophilia A is the most common form of hemophilia affecting individuals. Current treatment options include recombinant or concentrated plasma procoagulant. However, immunity to these treatment options as well as high treatment cost is common. This research models a treatment option involving P-selectin. P-selectin is a known precursor to tissue clotting factors already present in the body, and therefore can minimize the issue of immunity to treatment. The purpose of this research is to optimize the delivery of a P-selectin precursor in order to minimize clotting time and reduce immunity to drug therapy for hemophilia patients. In order to simulate this treatment, the drug P-sel-Ig was assumed to have been injected and reacted within the vein to produce an initial steadystate microparticle concentration. In COMSOL, as mass transport through a cylindrical vessel with fluid flow. This model measures the time it takes to accumulate enough fibrin to fully clot the wound. The model also optimizes microparticle concentration to minimize the time taken to clot the wound. The model can be adjusted for varying wound size, location, and time of formation. This model was validated in optimizing microparticle concentration for promoting the clotting of wounds. The literature value for wound clotting time is approximately 4.5 minutes. In order to achieve a complete wound clot, the clotting time from the model was approximately 35 minutes, which is within an order of magnitude from the literature value. This research defines clotting time as the number of minutes necessary to reach a 90% threshold fibrin density packing ratio. The optimal initial microparticle concentration was 2.66×10 5 mol/m 3 . In addition, the model showed that as wound size increases, the time necessary to close the wound also increases. The computation model demonstrated a range of initial microparticle concentrations necessary to provide adequate fibrin clot formation in response to the wound. The results of this model can potentially be used in optimizing the design of a regularly administered drug therapy for hemophilia patients to facilitate efficient clotting. This drug therapy would be cheaper treatment option because of its longer halflife. It would also prevent the formation of antibodies, which reduces the effectiveness of current treatment options.

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Procoagulant Microparticle Interaction; P-sel-Ig; Hemophilia A


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