Methods
The ethical committees of participating HTCs authorized enrollment in the ATHNdataset. The parents or guardians of eligible children either opted in or provided informed consent to share their child’s health information. Core data elements, including demographics, primary diagnosis, baseline factor activity levels, prescribed medications, inhibitor status, and insurance are submitted by each HTC.1 The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool Bleeding Score (ISTH-BAT BLS), factor activity level, and genotype were collected for participants in the My Life Our Future (MLOF ) genotype initiative. Additional data elements such as bleeding events, including detailed menstrual bleeding, medication usage, and joint range of motion could also be submitted. Core data elements are audited by ATHN for consistency. Many other data element’s collection and submission are left to the discretion of participating HTCs and are not audited. Because data elements such as bleeding events, medication usage, or detailed menstrual bleeding are likely underreported, this type of data was not subjected to further analysis.
The ATHNdataset was queried in June 2022 for hemophilia carriers under 18 years of age. Collected data included age, race, ethnicity, type of hemophilia (A or B), baseline factor activity level, genotype, and ISTH-BAT BLS. The ISTH-BAT BLS has been validated for use in children, and normal ranges are established for adults and children.5 An ISTH-BAT BLS of 3 or higher was determined to be abnormal for children under 18 years of age by Elbatarny et al.5 Although Elbatarny et al. initially established an ISTH-BAT score of 6 or higher as abnormal in adult women, subsequent analysis has shown a ISTH-BAT score of 5 or higher was abnormal for women aged 18-30.6 Since adolescents are biologically more similar to women age 18-30 (menstruating and at risk for post-partum hemorrhage) than children, we felt the revised definition of an abnormal ISTH-BAT score was more appropriate to use in adolescents aged 11-17. Doherty et al. did not revise the abnormal BLS for adolescents due to sample size limitations.6Additional support for this methodology is found in Jain et al.7 This study showed that a BLS of 5 or higher in adolescent girls was predictive of having a bleeding disorder. As previously described, we defined a BLS of 5 or higher as abnormal for adolescents and 3 or higher as abnormal for children.1The participant’s age at the time of BLS determination was used to determine if the score was abnormal or not. For subjects with multiple reported ISTH-BAT BLS we selected the earliest record. The one-stage factor activity level is the predominant methodology used to determine factor activity levels in the United States, and factor activity levels reported in this study were presumed to be from a one-stage assay. For subjects submitting more than one factor activity level, the lowest reported level (baseline) was used. The proportion of subjects who had a genotype determined was collected to describe the population. A detailed analysis of genetic information was beyond the scope of this study. Because this updated query covered a different timeline than prior studies of hemophilia carriers using the ATHNdataset, sample size differences were expected.
Descriptive statistics were used to define the population. Data sets with a sample size less than 50 were considered to be too small for valid statistical comparisons. Pearson’s Chi squared test, Fisher’s exact test, Wilcoxon rank sum and Welch Two Sample t-tests were used for group comparisons. When able to be measured, a p value of less than 0.05 was considered statistically significant. The original, de-identified data can be obtained by contacting ATHN at support@athn.org.