Mixing studies: Immediate mixing and repeat PTT aPTT after 1 hour Factor VIII
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12.5 seconds (reference range, 10.5 to 12.4)
67.6 seconds (reference range, <40) 39.6 seconds
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This patient's family history is helpful in eliminating a congenital hemostatic defect as a source of her hematuria. She has had successful surgery events in the past but now suffers with hematuria and deep bruising. An elevated aPTT value can be seen in anticoagulant therapy, particularly heparin, in clotting factor defects, and if a circulating inhibitor is present. Mixing studies in this patient show variable results with initial correction of the patient's aPTT and then subsequent prolongation upon incubation. A factor VIII inhibitor was considered as a likely explanation for the laboratory results and the low factor VIII assay value. Inhibitors or autoantibodies against factor VIII may develop in populations other than the hemophilia A population, where 10% to 30% develop these type of inhibitors. These inhibitors are directed against a portion of the factor VIII molecule and are time and temperature dependent. Once identified, the inhibitor should be quantitated using the Bethesda titer. In this procedure, equal volumes of pooled normal plasma that is platelet poor are mixed with patient platelet poor plasma at pH 7.4. The mixture is incubated for 2 hours and the PTT is repeated. If the patient plasma has anti-factor VIII activity, then some of the active factor VIII in the normal plasma will be affected. The level of inhibitor is seen as a percentage of the normal activity of the factor when compared to the control plasma. One Bethesda unit is equivalent to the inhibitor in which 50% factor activity will remain.
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