The Role of Race and Ethnicity in the Clinical Outcomes of Severe Hemophilia A Patients with Inhibitors.

Background: Repeatedly, it has been observed that inhibitors to factor VIII are more frequent in African American (AA) and Hispanic (H) patients with severe congenital hemophilia A than in Caucasian (C) patients. Large retrospective reviews have shown that the mortality rates between African American and Caucasian patients with hemophilia have been similar, although non-whites had significantly more bleeding complications, need for hospitalizations and joint limitations. One possible explanation suggested that whites were more likely to receive aggressive treatment strategies such as home infusion. In none of the above reviews were patients stratified by inhibitor status. Few non-white patients have been included in large studies of inhibitor development and natural history. The purpose of this study was to evaluate the impact of race and ethnicity on the clinical characteristics and outcomes of inhibitors in patients with severe hemophilia A.

Methods: This is a retrospective review of the repository database of the Hemophilia and Thrombosis Research Society (HTRS). Due to skewed distributions, non-parametric Kruskal-Wallis tests were used to test for racial differences.

Results: The HTRS database captured data from 658 hemophilia patients since January 2000. Within the HTRS registry, there were 562 patients with severe hemophilia A: 68.1% (n=383) Caucasian, 21.0% (n=118) African American, and 10.9% (n=61) Hispanic. In comparison to Caucasians, Hispanics had a higher age at hemophilia diagnosis (p-value <0.01), while there was not a significant difference with African-Americans (p-value =0.53). Amongst those subjects with a prior history of inhibitors, African-Americans and Hispanics had a higher family history of inhibitor development: 13.7% of C, 26.3% of AA (pwhite = 0.02), and 41.2% of H (pwhite = <0.01). In patients with a history of inhibitors, Caucasians reported the lowest prevalence of a history of Intracranial Hemorrhage (ICH): 15.8% of C, 29.8% of AA (pwhite = 0.03), and 20.6% of H (pwhite = 0.52). African-Americans reported the lowest rate of receiving ITT (64.9%), followed 76.5% in Hispanics and 84.9% in Caucasians. African-Americans also had the lowest success rate of ITT, 30.4% as compared to 35.3% in Hispanics and 60.3% in Caucasians. In comparison to African-Americans, Caucasians did not have a significantly higher rate of unrestricted function (p=0.13), while the rate was significantly higher in Hispanics (p=0.02).

Conclusion: While the HTRS database did not assess overall bleeding complications, it did show a significantly higher incidence of ICH in African-Americans versus Caucasian inhibitor patients, which could not be confirmed in non-inhibitor patients. It also appears, that fewer African-Americans and Hispanics are receiving immune tolerance therapy and that they have a lower success rate than Caucasians. However, there were insufficient patients studied to reach statistically significant conclusions. Hispanics did report significantly higher level of function. However, the HTRS survey does not use a very intricate, detailed tool to assess function. The above data proposes further investigation of bleeding risk across race/ethnicity in inhibitor vs. non-inhibitor populations. It also prompts us to look at larger databases to assess use and outcome of immune tolerance across races. Thirdly, it poses the question, whether there is a racial/ethnic difference in functional status and whether there could be variation in severity and outcome of bleeds.