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.