Concomitant X chromosome disorders, such as Turner syndrome and Klinefelter syndrome, can worsen bleeding symptoms in patients with hemophilia, according to a series of case studies published in Pediatric Blood & Cancer.
Hemophilia is an X-linked recessive disorder characterized by deficiencies in coagulation factors,, resulting spontaneous and/or trauma-induced bleeding that can lead to severe morbidity. To treat this disease holistically, physicians need to be aware of how other comorbidities may impact the bleeding phenotype.
The authors of this study described the case of a female patient who was diagnosed with hemophilia A at 10 months of age. Her initial presenting symptom was a large hematoma on her chest; further history-taking revealed multiple family members who were previously diagnosed with hemophilia A.
A test of factor VIII (FVIII) activity revealed that she had moderate-to-severe hemophilia A; her FVIII:C levels were found to be fluctuating between less than 1% and 4%. This patient was also found to have the 46, XX karyotype (skewed X-inactivation), which could be a contributory cause to her low FVIII:C levels.
Read more about hemophilia etiology
Upon follow-up, it was clear that the patient continued to have a severe bleeding phenotype, including significant muscle hematomas and hemarthroses. Her physicians prescribed factor prophylaxis with recombinant FVIII 3 times a week.
Upon the onset of menarche, the patient experienced heavy menstrual bleeding; however, this was well-controlled with the initiation of progestin-only pills. Her bleeding phenotype decreased in intensity as she got older; by late adolescence, she only needed infusions of factor prophylaxis once or twice weekly, depending on her clinical condition.
In 2 other case reports described by the authors, patients with Turner syndrome (45, X) and Klinefelter syndrome (47, XXY) appeared to experience a heavier bleeding phenotype than normal. The researchers also highlighted the fact that females with hemophilia are traditionally underrecognized or misdiagnosed.
“Although rare occurrences, education of pediatricians and emergency care providers on the occurrence of hemophilia in females and individuals with aberrant X chromosome copy number or expression in the diagnostic evaluation for hemophilia is critical, as these providers are often the first point of contact with bleeding concerns,” they said.
Soffer E, Coleman K, Batsuli G. The impact of concurrent X chromosome anomalies on diagnosis and bleeding phenotype in children with hemophilia: a single-institution case series. Pediatr Blood Cancer. Published online May 2, 2023. doi:10.1002/pbc.30400