What is the recommended treatment for individuals with hemophilia?

Recommended Treatment for Hemophilia

For individuals with severe and moderately severe hemophilia A without inhibitors, prophylaxis with factor VIII concentrates or emicizumab is strongly recommended over episodic (on-demand) treatment to prevent bleeding and joint damage. 1

Treatment Algorithm for Hemophilia A Without Inhibitors

Primary Treatment Strategy: Prophylaxis

Prophylaxis should be initiated as first-line therapy in all patients with severe hemophilia A (factor VIII <1 IU/dL) and moderately severe hemophilia A, as it provides large reductions in bleeding risk with minimal adverse events compared to treating bleeds as they occur. 1

Choice of Prophylactic Agent:

Either factor VIII concentrates or emicizumab can be used for prophylaxis, with selection based on availability, resources, patient preference, and treatment burden considerations. 1

• Factor VIII concentrate dosing: Standard prophylaxis uses 15-40 IU/kg body weight 2-3 times per week of plasma-derived or recombinant factor VIII. 1

  • Specific effective regimens include 25 IU/kg every other day or 30-40 IU/kg 3 times per week. 1
  • Extended half-life recombinant factor VIII concentrates allow less frequent dosing. 1

• Emicizumab: Administered subcutaneously on a weekly, biweekly, or every 4-week schedule, offering lower treatment burden. 1, 2

  • Provides similar bleeding rate reductions compared to factor VIII concentrates. 1
  • Particularly valuable for patients with difficult venous access or adherence challenges. 2
  • Long-term safety data remains limited, which influenced the conditional recommendation. 1

Resource-Limited Settings:

Low-dose prophylaxis with 10 IU/kg plasma-derived factor VIII 2-3 times per week is an effective alternative when standard-dose options are unavailable, as it still prevents joint bleeds and damage compared to episodic treatment. 1

Timing of Prophylaxis Initiation:

Primary prophylaxis should begin at 1-2 years of age, ideally before the first joint bleed or within the first 50 exposure days to factor VIII. 1, 3

Product Selection Considerations:

For previously untreated patients, plasma-derived factor VIII may be preferred over standard half-life recombinant factor VIII during initial prophylaxis, as recombinant products are associated with increased inhibitor development risk (26-31% vs lower rates with plasma-derived). 1

Treatment Algorithm for Hemophilia A With Inhibitors

Prophylaxis Strategy:

Emicizumab is suggested over bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate) for prophylaxis in patients with inhibitors, offering greater effectiveness, lower cost, and reduced treatment burden. 1

Prophylaxis is recommended over episodic treatment even in patients with inhibitors. 1

Acute Bleeding Management:

For breakthrough bleeding on emicizumab, use recombinant factor VIIa (eptacog alfa) rather than activated prothrombin complex concentrate due to thrombotic risk when combined with emicizumab. 1, 2

For invasive procedures in inhibitor patients, either recombinant factor VIIa or activated prothrombin complex concentrate can be used, though recombinant factor VIIa requires more frequent administration. 1

Inhibitor Eradication:

Immune tolerance induction should be attempted in patients with high-responding inhibitors, using either low-dose (50 IU/kg 3 times per week) or high-dose (200 IU/kg daily) factor VIII regimens. 1

Treatment Algorithm for Hemophilia B

Prophylaxis with extended half-life recombinant factor IX concentrates administered once every 1-2 weeks is recommended over episodic treatment for severe and moderately severe hemophilia B. 1

Standard prophylaxis dosing is 20-60 IU/kg twice per week for hemophilia B. 1

Surgical Management

For major invasive procedures in hemophilia A without inhibitors, either continuous infusion or bolus dosing of factor VIII concentrates can be used, with continuous infusion consuming lower amounts of concentrate. 1

Adjunctive Therapy

Tranexamic acid 10 mg/kg intravenously can be used for 2-8 days to reduce hemorrhage and factor replacement needs during and after dental extractions in hemophilia patients. 4

Critical Pitfalls to Avoid

• Never combine emicizumab with activated prothrombin complex concentrate due to high thrombotic microangiopathy and thromboembolic event risk. 2
• Avoid episodic (on-demand) treatment as primary strategy in severe hemophilia, as it fails to prevent progressive joint destruction leading to crippling arthropathy. 1
• Do not delay prophylaxis initiation in children, as early primary prophylaxis prevents joint damage and may reduce inhibitor development risk. 1, 3
• Infuse factor VIII no faster than 1 mL/minute to avoid hypotension. 4