Hemophilic Dog Model For Evaluating Hemostatic Efetcacy Of Plasma Protein Fractions

About 15% of patients with hemophilia A develop inhibitors to Factor VIII. Because in many cases the inhibitor renders the patient refractory to treatment with Factor VIII, plasma protein fractions designed to bypass the inhibitor have been developed. In the USA these are referred to genetically as Anti Inhibitor Ccrplex Concentrates (AICCs). Development of AICCs has been hampered by lack of a suitable irodelin which to judge hemostatic efficacy. Similarly, lack pf a model has impeded research on the mechanism of action Of AICCs. Therefore, we chose to evaluate AICCs in dogs with hemophilia A, reasoning that a material capable of bypassing & Factor VIII inhibitor should be effective in Factor VIII deficient recipients with or without inhibitors. Under local anesthesia a standardized gingival biopsy was performed losing a flexible plastic template and a modified scalpel handle holding two #11 Bard-Parker blades. The parallel time is ions were 5 mm long, 2 nm apart, and 1.5 mm deep. The tissue block thus defined was removed by sharp dissection. In normal dogs, bleeding from this wound ceased in 5 ± 2min, the wound was filled with concave clot, and bleeding did not recur. In contrast, hemophilic dogs formed an abnormal (very large) clot, and rebled for several days if untreated. The hematocrit usually dropped by 2-10 percentage points in 24 hr of uncontrolled bleeding. An experimental AICC fraction under development by Cutter Laboratories was evaluated in 5 dogs, and shown to be hemostatically effective. The dose required to achieve hemostasis was 25-75 units/kg; in some dogs a second dose was required 6 hr after the first dose to maintain hemostasis. A single dog with a low titer inhibitor to Factor VIII was successfully treated with 39 u/kg, followed by a repeat dose of 39 u/kg 6 hr after the first dose. We conclude that this AICC preparation brings about nemostasis in Factor VIII deficient individuals with or without inhibitors to Factor VIII.