Improved Factor VIII Inhibitor Evaluation

Study Overview
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Brief Summary
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Commercial one and two-stage factor VIII assays may not detect some clinically significant inhibitor antibodies. The purpose of the proposed study is to standardize and validate a platelet-based factor VIII activity assay with greater sensitivity to clinically important inhibitory antibodies. Investigators will evaluate the platelet-dependent inhibitory activity vs. conventional inhibitory activity in stored patient plasmas and correlate to bleeding histories

Detailed Description
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Factor VIII activity assays are used to diagnose hemophilia A, to monitor treatment of these patients, to determine when inhibitory antibodies against factor VIII have developed, and to evaluate the activity of engineered pharmaceutical factor VIII products. Factor VIII activity has been measured with one and two-stage assays for more than fifty years. However, all existing assays have major shortcomings that are recognized by the FDA, the International Society for Thrombosis and Haemostasis, and pharmaceutical companies. The major deficiencies that have been identified are: 1) Factor VIII activity levels do not predict the risk of bleeding in patients with inhibitory antibodies. The degree of inhibition in these assays is less than required to explain patient bleeding. 2) The assays are only accurate over a range of 1 - 100% of normal factor VIII activity, while values of 0.1 - 1% are also clinically important. 3) The different approved assays give discrepant values for recombinant pharmaceutical factor VIII products, with a range of 2-fold difference between assays. This can lead to clinically important differences in dosing of factor VIII products from one region to another with corresponding risk of thrombosis or bleeding. The preliminary data identify an additional deficiency of commercial assays that has not been anticipated. Commercial one and two-stage assays may not detect some clinically significant inhibitor antibodies. Thus, the purpose of the proposed studies is to standardize and validate a platelet-based factor VIII activity assay with greater sensitivity to clinically important inhibitory antibodies.

Official Title
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Improved Factor VIII Inhibitor Evaluation

Conditions
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Hemophilia, Hemophilia A

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hemophilia A presence of inhibitory antibodies Exclusion Criteria: none
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Emory University<br>Samples obtained at and shipped from Emory University | |
| University of Michigan<br>Samples obtained at and shipped from University of Michigan | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding exceeds risk predicted by factor VIII assay | annual bleeding rate exceeds the rate predicted from the residual factor VIII activity | 1 year | 
| Bleeding is in accord with the risk assigned by platelet-dependent factor VIII activity | annual bleeding rate is within the predicted range from residual factor VIII activity | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor VIII, inhibitor, assay