Surveillance of Hemophilia in Indiana: A Preliminary Report

Background and objectives: Hemophilia is a rare heritable bleeding disorder resulting from missing or deficient levels of factor VIII or factor IX. Hemophilia related complications result in high utilization of health care resources and include severe, debilitating chronic joint disease. In 1998, Soucie et al. published the results of a six-year surveillance study investigating the incidence and prevalence of hemophilia in six U.S. states. The study also described the relationship between mortality and morbidity and each patient's primary source of hematologic care (i.e. whether each patient had visited a federally designated hemophilia treatment center (HTC)). The Indiana Hemophilia Surveillance Project (IHSP) aims to identify all persons with hemophilia who resided in Indiana in 2011-2013, to calculate the prevalence and incidence of hemophilia in Indiana, and to determine the percentage of patients cared for at a federally recognized HTC. The IHSP further aims to compare morbidity and mortality data to the results of the Soucie et al. study.

Methods: A hemophilia case in this study is defined as a male with physician-diagnosed hemophilia A or B and a measured baseline factor VIII or IX activity level less than 50%. A retrospective review of medical charts and other records was conducted to identify hemophilia cases during the surveillance years from 2011-2013. Case finding methods involved obtaining medical information from a variety of medical care resources including: HTCs in Indiana and surrounding states, hospitals, vital records, Indiana's birth defects registry, hospital and administrative claims data from the Regenstrief Institute, Medicaid claims data, clinical laboratories, specialty pharmacies, hematology/oncology clinics, and primary care physicians. Demographic and clinical data were collected on all identified cases. Data collected included: demographic information, clinical characteristics, joint health assessments, insurance status, clotting factor product utilization and cost, source of hemophilia care, hospitalizations and emergency room visits, and mortality information. Associations between clinical characteristics were assessed for statistical significance using chi-square and fisher's exact tests. Incidence was calculated by using the number of births from prevalent cases during the three surveillance years as the numerator and the number of live male births in Indiana for each year as the denominator.

Results: 704 hemophilia cases were identified in Indiana in 2011-2013. Of those cases, 456 (64.8%) had factor VIII deficiency and 248 (35.2%) had factor IX deficiency. The median age of the population was 25 years. 453 cases (64.3%) were adult patients and 251 cases (35.7%) were pediatric patients under 18 years. Among those with known severity levels (n=685), 233 (33.1%) were severe, 185 (26.3%) were moderate, and 267 (37.9%) were mild. Overall, 81.7% of the hemophilia patients identified visited an HTC at least once during the three year study period, which was the minimum requirement for being considered a patient of an HTC. Age-adjusted prevalence was 21.8 cases per 100,000 males; 14.3 per 100,000 for factor VIII and 7.5 per 100,000 for factor IX. Mean incidence of hemophilia over the three year study period was 1:4059 live male births in Indiana. 24 cases (3.4%) died within the study period; 4.2% of the deaths occurred in HIV positive patients. Of those with a known cost of clotting factor (n=184), the average and median cost of factor over the three year period was $375,532 and $71,525 respectively.

Conclusions: There was a significantly higher percentage of patients seen at an HTC (81.7%) as compared to the results of the Soucie et al. study (67%; p =<0.001). Indiana has a 62% higher prevalence and 24% higher incidence of hemophilia than in the Soucie et al. study. A high frequency of factor IX deficiency associated with a founder mutation in the Amish community contributes to the higher incidence of factor IX deficiency in Indiana, with a 64% higher percentage of factor IX deficiency among hemophilia cases. The higher prevalence likely reflects improved survival and increased utilization of HTCs in the past two decades. This report is the first follow-up study of the original Soucie et al. report using the same systematic approach. Further analysis on mortality and morbidity complications in this population will be completed and reported in future reports.