Current State of Moderate Congenital Haemophilia A and the Need for Preventive Treatment.

INTRODUCTION: The severity of haemophilia A is classified by the degree of factor VIII (FVIII) deficiency, rather than by clinical manifestations. However, FVIII activity alone does not necessarily accurately reflect clinical severity such as bleeding tendency, and patients with mild-to-moderate haemophilia A can experience significant disease burden. AIM: This narrative review explores the clinical relevance of non-severe haemophilia A (focusing on moderate disease), and examines the profile of patients with, and the evidence supporting the use of prophylaxis to manage, this disease form. METHODS: A PubMed search was conducted (no language/date limits), using terms including 'hemophilia' or 'haemophilia', and 'moderate', 'nonsevere' or 'non-severe', with the names of prophylactic agents. RESULTS: Some patients with moderate haemophilia A experience significant disease burden (in terms of bleeding frequency and joint damage), diminished health-related quality of life and marked economic impact. In addition, variation in bleeding phenotype across disease severity levels has been recognised, such that patients with moderate disease may have a severe phenotype and experience more frequent spontaneous bleeds than those with a mild phenotype. Few studies have specifically assessed outcomes associated with prophylaxis in patients with moderate haemophilia A. However, available data suggest that prophylaxis with FVIII concentrates and non-factor treatments (i.e. emicizumab) provides beneficial effects in terms of bleeding frequency and joint health. CONCLUSION: Severity classification alone is insufficient to predict bleeding tendency, and joint bleeding and joint injury are observed in patients with moderate disease. As such, routine prophylaxis may be recommended for some patients with moderate haemophilia A.