Discrepant Hemophilia A: An Underdiagnosed Disease Entity

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.

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.

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.

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.