Discussion
Although hemophilia is thought to occur in about 1 in 3500–5000 male
births without major geographic or ethnic
differences,1,2 the actual number of affected patients
reported from low-income countries (LIC) is significantly lower than
expected. For example, Uganda with a current population of 45 million
and 1.7 million births yearly reported a total of only 221 individuals
living with hemophilia in 2018.3 This wide disparity
between the expected number and the actual number of individuals living
with haemophilia in Uganda is most likely due to a high number of
undiagnosed patients combined with premature death due to bleeding. Data
from the World Federation of Hemophilia (WFH) show a consistent
relationship between the economic status of individual countries and the
prevalence of hemophilia.4 As a group, countries with
a gross national product lower than $2000 report only about one third
of the expected total number of individuals with
hemophilia.4
While almost all patients with severe hemophilia (defined as
<1 percent factor VIII or IX activity) in high-income
countries (HIC), are diagnosed during the first few months of
life,5,6 diagnosis is often delayed in LIC due to a
dearth of hematologists, basic knowledge about bleeding disorders, and
hematology laboratory infrastructure. Our patient bled for two weeks
after circumcision, was hospitalized to evacuate a hematoma, and was not
diagnosed with hemophilia until he presented to the hematology clinic.
We diagnosed our patient with congenital severe hemophilia A with milder
than expected clinical phenotype. Milder-than-expected severity of
hemophilia as we found likely results from differences in the specific
causal hemophilia mutation, as well as innate differences in the genetic
factors that control each individual’s anticoagulant and fibrinolytic
systems.7,8 Similar to our patient, Shapiro et al.
diagnosed severe congenital hemophilia in a 33-year-old enlisted US
Marine with 10 years of active service when he presented with bleeding
after routine shoulder surgery.9
Though the absence of a family history of bleeding in our patient
suggests sporadic haemophilia due to a spontaneous mutation, we were
unable to perform genetic testing of the patient and his mother, or to
obtain a reliable history of the patient’s grandparents, plus their
siblings and the descendants of those siblings. Considering these
factors plus the possibility that familial severe hemophilia A may be
similarly mild in our patient’s asymptomatic brothers, we advised them
to be screened with an aPTT test.
An alternative explanation for bleeding with isolated prolonged aPTT and
low factor VIII activity such as acquired hemophilia A from the
development of autoantibodies against endogenous factor VIII was
considered. However, this was ruled out based on the patient’s excellent
general health, relatively young age, and full correction of his aPTT
when mixed 1:1 with normal plasma.
This case highlights the need to improve general knowledge about
bleeding disorders among health workers and the community, and upgrade
the quality of hematology laboratory infrastructure in LIC. This patient
bled for 2 weeks before he was diagnosed with severe hemophilia. One way
to accomplish these objectives is by building collaborative
relationships between medical organizations in LIC and their
counterparts in HIC. As an example, the hematology clinic where this
patient was diagnosed is the only one in Western Uganda – a region with
a population of 10 million. It would not exist but for collaboration
between Makerere University in Uganda and Baylor College of Medicine in
Texas, United States to train haematologists in sub-Saharan Africa
(SSA). This Global Hematology-Oncology Pediatric Excellence (Global
HOPE) initiative from the Texas Children’s Cancer and Hematology
Centers, in partnership with Makerere University College of Health
Sciences, the affiliated Mulago National Referral Hospital, and Uganda
Ministry of Health has graduated three sets of fellows from its 2-year
training program and currently enrolls 10 trainees from five SSA
countries.10 More opportunities for training like this
one will facilitate the comprehensive care of individuals with
hemophilia and secondarily stimulate the growth of organizations that
support individuals with hemophilia plus improve awareness in the
general population of LIC.