What is the primary management for Haemophilia A (Hemophilia A)?

Primary Management of Hemophilia A

Prophylaxis with Factor VIII (FVIII) replacement products is the standard of care for patients with severe Hemophilia A, requiring regular intravenous infusions at least once per week to prevent spontaneous bleeding and progressive joint destruction. 1

Standard Treatment Approach

First-Line Therapy: FVIII Replacement

• Regular prophylactic FVIII infusions are the cornerstone of management for severe Hemophilia A (factor VIII activity <1% of normal), administered intravenously at least weekly to maintain hemostasis and prevent spontaneous bleeding episodes 1
• Both plasma-derived and recombinant FVIII concentrates are effective options, with recombinant products including standard half-life and extended half-life (EHL) formulations 1, 2
• Extended half-life FVIII molecules allow for less frequent dosing while maintaining effective prophylaxis, improving treatment adherence and reducing burden 2

Alternative Prophylactic Option: Emicizumab

• Emicizumab (a subcutaneous FVIII-mimetic bispecific monoclonal antibody) is approved for prophylaxis in Hemophilia A patients with or without inhibitors, administered every 1-2 weeks 1
• Despite less frequent dosing, FVIII replacement is still required for breakthrough bleeding episodes or surgical procedures when using emicizumab 1

Treatment Algorithm by Severity

Severe Hemophilia A (Factor VIII <1%)

• Primary prophylaxis should be initiated after the first joint bleed and/or before age 2 years to prevent progressive joint deterioration and hemophilic arthropathy 3
• Dosing frequency: At least once weekly for standard half-life products; extended intervals possible with EHL products 1, 2

Moderate Hemophilia A (Factor VIII 1-5%)

• Patients may have bleeding phenotype similar to severe disease and should be managed accordingly 1
• Episodic or prophylactic replacement based on individual bleeding pattern 1

Mild Hemophilia A (Factor VIII 5-40%)

• On-demand treatment for bleeding episodes or before procedures 1
• Desmopressin (DDAVP) can be used in patients with factor VIII levels >5% to maintain hemostasis during surgical procedures or reduce bleeding with spontaneous/traumatic injuries 4

Management of Inhibitor Development

Critical Complication

• 20-35% of severe Hemophilia A patients develop neutralizing alloantibodies (inhibitors) against infused FVIII, representing the most serious treatment complication 1, 5
• Prior to initiating treatment, verify factor VIII coagulant activity levels are >5% and exclude presence of factor VIII autoantibodies 4

Treatment for Patients with Inhibitors

• Bypassing agents (recombinant activated Factor VII or activated prothrombin complex concentrate) are used when bleeding does not respond to FVIII replacement 1, 5
• Immune tolerance induction (ITI) with regular FVIII infusions is the standard approach to eradicate inhibitors, successful in approximately 70% of patients 1, 5
• Emicizumab prophylaxis is an effective alternative for patients with inhibitors 5

Emerging Therapies

Gene Therapy

• AAV-based gene therapy (such as valoctocogene roxaparvovec) uses recombinant adeno-associated virus vectors to transfer functional F8 genetic information into hepatocytes, enabling long-term endogenous FVIII production after a single IV infusion 1
• This represents a potentially curative approach but requires careful monitoring for hepatotoxicity and immune responses 1

Critical Monitoring Requirements

Before Treatment Initiation

• Verify factor VIII coagulant activity levels and exclude inhibitor presence 4
• Assess serum sodium (particularly important if considering desmopressin) 4

During Treatment

• Monitor for breakthrough bleeding episodes, particularly when FVIII levels are at trough 1
• Serial monitoring of factor VIII levels, especially during surgical procedures or acute bleeding 4
• Early prophylaxis may prevent inhibitor development, as multiple genetic and environmental factors are involved 3

Common Pitfalls to Avoid

• Do not rely on on-demand treatment alone for severe Hemophilia A, as this does not prevent progressive joint deterioration leading to crippling arthropathy 3
• Do not use desmopressin in patients with factor VIII levels <5% or in those with severe disease, as it is ineffective 4
• Do not delay inhibitor screening in patients with poor response to FVIII replacement, as early detection and ITI initiation improves outcomes 5
• Ensure adequate venous access for prophylaxis in young children, though central venous catheters carry risks of infection and thrombosis 6