This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: Following dosing of recombinant Factor Vila 90 mcg/kg in hemophiliacs, platelet contractile force (PC F), clot elastic modulus (CEM) and thrombin generation time (TGT) normalize. These parameters will change comparably to the following established clotting parameters: Thromboelastography (TEG), Rotational Thromboelastography (ROTEG), in vitro thrombin generation, thrombin-antithrombin complex, Prothrombin Fragment 1.2, Factor VII activity and D-dimer.
Specific Aims : a. Document baseline TGT, PCF and CEM abnormalities in hemophiliacs with and without spontaneous factor VIII inhibitors. Secondly, document clotting deficiencies utilizing the TEG4!>and ROTEG4!>clotting parameters as well as assays detecting thrombin generation, TAT, Prothrombin Fragment 1.2, Factor 7 activity and D-dimer. b. Establish the extent by which TGT, PCF and CEM normalize in the above patients following the administration of rFVlla 90 mcg/kg. Secondly, document the extent by which clotting deficiencies normalize utilizing the TEG4!>and ROTEG4!>clotting parameters, as well as assays detecting thrombin generation, TAT, Prothrombin Fragment 1.2, Factor 7 activity and D-dimer.
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