Abstract
Background: The available methods for measuring factor VIII (FVIII) activity suffer reportedly from lack of sensitivity and precision in the <1 IU dL(-1) range. This precludes correlation of clinical phenotype with FVIII levels. Objectives: To study a possible association between clinical phenotype in patients with FVIII levels <1 IU dL(-1). Methods/Results: The FIXa-driven FVIII assay (FVIII-CAT) has a detection limit of 0.05 IU dL(-1). For the range of 0-2 IU dL(-1) FVIII, the intra-assay coefficient of variation (CV) is around 2% and the inter-assay CV is about 8%. We tested 30 hemophiliacs with FVIII: C between <1 and 6 IU dL(-1) as measured in the one-stage clotting assay using the FVIII-CAT assay. For genetic defects related to moderate hemophilia, the FVIII-CAT test finds FVIII levels that are in good agreement with those determined with the one-stage assay. Of the 21 hemophilic patients with FVIII <1 IU dL(-1), four patients exhibited a mild bleeding phenotype. When we applied TF-initiated thrombin generation, patients with a mild clinical phenotype showed significantly higher endogenous thrombin potentials. Conclusion: The novel developed FVIII assay measures accurately FVIII levels below 1 IU dL(-1). Its application demonstrated that the clinical heterogeneity in individuals with <1 IU dL(-1) FVIII is not associated with their FVIII level.
Original language | English |
---|---|
Pages (from-to) | 1549-1555 |
Journal | Journal of Thrombosis and Haemostasis |
Volume | 9 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2011 |
Keywords
- factor IXa-driven thrombin generation
- FVIII-assay
- hemophilia A