Discrepant Hemophilia A: An Underdiagnosed Disease Entity.

Objectives: The term discrepant hemophilia A (DHA) denotes the discrepancy between factor VIII activity (FVIII:C) measured by different assay methodologies in patients with nonsevere hemophilia A (HA). The objective was to review the characteristics and the current understanding of mechanisms contributing to assay discrepancy in DHA.

Methods: Characteristics of the DHA patients treated were examined by retrospective chart review. In addition, a literature review was performed to determine the current understanding of DHA.

Results: Three cases of DHA were diagnosed based on bleeding phenotype: 2 cases represented missed diagnoses of HA, and 1 represented misclassification of hemophilia severity. The revised diagnosis and classification of hemophilia directly affected clinical management. Review of the literature identified 18 articles with an estimated pooled prevalence of 36% (95% CI, 23%-56%; I2 = 85%; P < .01) among nonsevere HA. Furthermore, literature indicated that DHA is a feature of how different FVIII gene mutations affect FVIII:C activity within different assay methodologies.

Conclusions: Our experience and literature review suggested that DHA is not only a laboratory phenomenon-it can affect clinical management in a subset of patients. A high index of suspicion for DHA is necessary while evaluating bleeding patients and/or classifying nonsevere HA.