Compared to individuals with severe hemophilia, diagnosis may prove more challenging in those with mild-to-moderate disease, and there can be significant heterogeneity in symptoms and management needs. However, there is a dearth of research focused on treatment options and outcomes in these patients, according to a paper published in Haemophilia by Rajpurkar et al.1 Many patients have shifted from severe to mild hemophilia phenotype due to treatment advances in recent years, further highlighting the need to understand the unique needs of individuals with mild to moderate hemophilia A and hemophilia B in order to optimize care and quality of life.
Because of substantial variability in factor FVIII (FVIII) levels and bleeding symptoms in these patients, normal screening results may obscure the diagnosis. “In contrast to patients with severe hemophilia, patients with mild to moderate hemophilia usually do not suffer from spontaneous joint bleeds in childhood – therefore, diagnosis may occur later in life during surgery or trauma,” Annette Von Drygalski, MD, PharmD, hematologist, professor of medicine at the University of California, San Diego, School of Medicine, and director of the Hemophilia and Thrombosis Treatment Center at UC San Diego Health, told us in an interview.
“Since the diagnosis is not known at the time of these events, they may suffer from undue or dangerous bleeding until a diagnosis is made later,” she said. In an example from her practice, she described a 58-year-old male patient undergoing knee surgery with undiagnosed mild hemophilia A. He had severe unanticipated bleeding with large hemarthrosis and hematomas involving the leg and requiring blood transfusions. Clotting assays were performed, and results were abnormal with a FVIII level of 6% (normal above 100%). The patient received large amounts of FVIII concentrates and developed an inhibitor against FVIII, which resulted in further bleeding complications.
Rajpurkar et al. noted that while the results of 1-stage and chromogenic factor assays generally indicate concordant FVIII levels in patients with moderate and severe hemophilia A, there may be a discrepancy between assays (with one showing higher FVII levels than the other) in approximately 30% of those with mild hemophilia A. Accordingly, the “use of both assays for the measurement of FVIII levels in all patients with mild haemophilia A is recommended,” they wrote.1 Additionally, genetic screening is important in confirming the diagnosis and distinguishing between bleeding disorders.
Because bleeding episodes may be less frequent or pronounced in patients with mild-to-moderate hemophilia, they may lack knowledge about their disease and how to self-administer factor concentrates, potentially leading to delays in the management of bleeding episodes. “These delays can lead to musculoskeletal complications, including haemophilic arthropathy, leading to pain and decreased range of motion in the affected joints, even after a single bleeding episode in some cases,” wrote Rajpurkar et al.