People living with inherited bleeding disorders (including those with mild and moderate hemophilia and females affected by hemophilia) face persistent unmet needs that are often overlooked in clinical research and treatment guidelines. About twenty percent of mild hemophilia cases experience serious bleeding episodes, challenging current assumptions of their benign course.
Unmet needs
Diagnosis and awareness: Patients with mild and moderate hemophilia often face a delayed or missed diagnosis, leading to unrecognized and untreated bleeding episodes. The classic view that hemophilia severely affects only males perpetuates underdiagnosis, especially in females, where symptoms may be minimized or disregarded by clinicians, resulting in inappropriate care and impaired quality of life.
Education: There is a significant lack of education for both patients and health care providers; individuals may not recognize their bleeding risks or the need for prompt treatment, while many clinicians lack awareness about hemophilia’s impact in women and people with non-severe disease.
Underdiagnosed and misclassified
Women and girls with non-deletional or carrier status can have symptoms like men with mild hemophilia but are often misdiagnosed or labeled merely as “carriers.” The outdated terminology fails to reflect their clinical realities. Males are typically diagnosed at birth or early infancy, whereas females with comparable clinical symptoms are diagnosed much later, sometimes decades into life.
Lack of inclusion in clinical trials
Women and mild-to-moderate hemophilia patients are frequently excluded from clinical studies and registry data. This exclusion perpetuates gaps in evidence and limits generalizability of treatment guidelines.
Absent in treatment guidelines
Major hemophilia guidelines (e.g., WFH) currently focus predominantly on severe hemophilia, overlooking mild and female presentations. Women’s specific bleeding risks and nuanced pathophysiology remain underrepresented.
Women face unique hemorrhagic challenges: menstruation, childbirth, and hormonal fluctuations are rarely addressed in protocols.
Clinical engagement: Mild and moderate patients (and especially women) often remain less engaged with specialized treatment centers and the wider bleeding disorder community, missing out on optimal care and peer support.
Quality of life: Despite advances in therapy, many still experience bleeding episodes, joint damage, absenteeism from school/work, and difficulties in personal relationships.
Guideline limitations: Traditional clinical guidelines and eligibility criteria for both novel and established therapies skew toward severe hemophilia and male patients, systematically excluding those with mild/moderate disease and many females from receiving new treatments or even prophylaxis regimens.
Clinical trial exclusion: Historically, clinical trials for promising new therapies (such as gene therapy, non-factor products, or rebalancing agents) have excluded individuals with mild/moderate disease and female patients. As a result, evidence guiding optimal management for these populations is lacking, perpetuating therapeutic inequities.
Making the case for expanded access
Equity in care: As novel therapies are transforming outcomes for severe hemophilia and male patients, equity demands expanding access to include mild/moderate cases and females. These populations also suffer from bleeding episodes, joint damage, and impaired life quality, which new treatments can ameliorate.
Diagnostic update: Modern definitions now recognize symptomatic females and the full spectrum of disease severity; thus, therapies should be considered based on clinical need rather than traditional classification or gender norms.
Health outcomes: Offering appropriate prophylaxis and new agents to these disadvantaged groups can reduce bleeding, preserve joint health, and improve participation in school, work, and social life.
Stakeholder engagement: Guideline committees, regulators, and industry must redesign trials and policies to include these populations, with dedicated research to define optimal dosing, efficacy, and safety for all people with inherited bleeding disorders.
Education and advocacy: Enhanced patient and provider education, community engagement programs, and targeted screening are essential to address diagnostic gaps and facilitate access.
Conclusion
For too long, people with mild and moderate hemophilia and females with bleeding symptoms have been excluded from the benefits of therapeutic advances. Closing this gap requires updating diagnostic criteria, educating health care providers, and ensuring that current and novel therapies (including gene therapies and non-factor agents) are accessible and studied in these underserved populations. This is a critical advance toward true health equity in bleeding disorder management.
Akshat Jain is a pediatric hematology-oncology physician.
