What is the treatment for acquired hemophilia?

Treatment of Acquired Hemophilia A

All patients with acquired hemophilia A require immediate dual-track therapy: bypassing agents (recombinant activated factor VII or activated prothrombin complex concentrates) for acute bleeding control, and immunosuppressive therapy initiated immediately upon diagnosis to eradicate the autoantibody. 1

Acute Bleeding Management

First-Line Hemostatic Therapy

Initiate anti-hemorrhagic treatment in all patients with active severe bleeding, regardless of inhibitor titer or residual FVIII activity. 1

Bypassing agents are the standard of care:

• Recombinant activated factor VII (rFVIIa): 90 μg/kg bolus every 2-3 hours until hemostasis is achieved 1, 2

  • For acquired hemophilia specifically, 70-90 μg/kg every 2-3 hours is effective 2
  • Continue until bleeding stops, typically 24-72 hours depending on severity and location 1
  • Efficacy rate of 90% when used as first-line therapy 1

• Activated prothrombin complex concentrates (aPCC): 50-100 IU/kg bolus every 8-12 hours, maximum 200 IU/kg/day 1

Neither agent is universally superior; choice depends on availability, patient comorbidities, and thrombotic risk profile. 1 The elderly population with acquired hemophilia often has cardiovascular risk factors (smoking, hypertension, diabetes, atherosclerosis), making thrombotic complications a significant concern with rFVIIa (7.2% incidence in one series). 1

Alternative Hemostatic Options (Only if Bypassing Agents Unavailable)

• Human FVIII concentrates or desmopressin: Only use when bypassing therapy is unavailable and inhibitor titer is very low 1
• If first-line bypassing agent fails: Switch to the alternative bypassing agent 1
• Prophylactic bypassing agents: Required before any minor or major invasive procedures 1

Critical Pitfall

Do NOT combine rFVIIa and aPCC except in life- or limb-threatening bleeds due to thrombotic risk. 1 Tranexamic acid is contraindicated with aPCC. 1

Immunosuppressive Therapy for Inhibitor Eradication

Immediate Initiation Required

Begin immunosuppressive therapy immediately upon diagnosis in all patients, even those without active bleeding. 1 Mortality without treatment is 41%, reduced to 20% with immunosuppression (11% directly inhibitor-related). 1

First-Line Immunosuppression

Corticosteroids alone or combined with cyclophosphamide:

• Prednisone: 1 mg/kg/day PO for 4-6 weeks 1

  • Monotherapy achieves 60-70% complete response 1

• Combination therapy (prednisone + cyclophosphamide): For patients already on steroids for other conditions or with high-titer inhibitors 1

  • Cyclophosphamide: 1.5-2 mg/kg/day for maximum 6 weeks 1
  • Combination achieves 70-80% response rate 1
  • One randomized trial (n=31) showed 84% complete response with combination therapy 1

Second-Line Immunosuppression

Rituximab: Use if first-line therapy fails after 4-6 weeks, is contraindicated, or in very elderly patients (>75 years) who may not tolerate steroids/cyclophosphamide 1, 3

• Rituximab has been used successfully in refractory cases, high-titer inhibitors, relapses, and life-threatening bleeds 3
• Consider as first-line in the very elderly given better tolerability profile 3

Therapies NOT Recommended

High-dose intravenous immunoglobulin is NOT recommended for inhibitor eradication. 1

Immunoabsorption/plasmapheresis: Reserve only for life-threatening bleeds or clinical research settings 1

Monitoring and Follow-Up

After achieving complete sustained response:

• Months 1-6: Monitor aPTT and FVIII:C monthly 1
• Months 6-12: Every 2-3 months 1
• Year 2 and beyond: Every 6 months 1

Relapse occurs in approximately 33% of patients, often within 6 months of starting treatment. 3 All relapses can be successfully retreated. 3

Special Considerations

Thromboprophylaxis Post-Remission

Following inhibitor eradication and sustained response, implement thromboprophylaxis according to ACCP guidelines, especially in patients with very elevated FVIII:C levels. 1 The rebound hypercoagulability after autoantibody clearance poses thrombotic risk.

Prevention of Iatrogenic Bleeding

• Avoid central venous access when possible; even peripheral venous access can cause significant bleeding 1
• Delay elective surgery until inhibitor eradication 1
• Cover all invasive procedures with prophylactic bypassing agents 1

Prognostic Factors

Advanced age (>75 years) and lack of treatment predict poor survival. 3 Overall mortality is 25%, with most deaths occurring in untreated patients. 3 The 83% response rate to immunosuppression in treated patients emphasizes the importance of immediate therapy initiation. 3