From the Guidelines
Acquired hemophilia A with concurrent low fibrinogen activity is a rare but serious coagulation disorder requiring prompt diagnosis and treatment, and management should focus on controlling bleeding with bypassing agents and fibrinogen replacement, while eliminating the inhibitor with immunosuppression. This condition typically presents as acquired hemophilia A (caused by autoantibodies against factor VIII) alongside hypofibrinogenemia. The most common etiologies include:
- Autoimmune disorders (such as systemic lupus erythematosus, rheumatoid arthritis)
- Malignancies (particularly lymphoproliferative disorders and solid tumors)
- Medications (penicillins, sulfonamides, interferon)
- Pregnancy/postpartum state
- Idiopathic causes (approximately 50% of cases) 1. The mechanism involves autoantibodies targeting factor VIII, impairing the intrinsic coagulation pathway, while hypofibrinogenemia may result from increased consumption (disseminated intravascular coagulation), decreased production (liver disease), or antibodies against fibrinogen.
Management requires a dual approach:
- Controlling bleeding with bypassing agents (recombinant factor VIIa 90 μg/kg every 2-3 hours or activated prothrombin complex concentrate 50-100 U/kg every 8-12 hours) 1
- Fibrinogen replacement (cryoprecipitate or fibrinogen concentrate 4 g initially, then as needed to maintain levels >100 mg/dL)
- Simultaneously eliminating the inhibitor with immunosuppression (prednisone 1 mg/kg/day with cyclophosphamide 1-2 mg/kg/day for 6-8 weeks, or rituximab 375 mg/m² weekly for 4 weeks) 1. Monitoring should include factor VIII levels, inhibitor titers, fibrinogen levels, and surveillance for underlying conditions, as treating the primary cause often helps resolve the coagulation abnormalities.
From the Research
Acquired Haemophilia A and Low Fibrinogen Activity
- Acquired haemophilia A (AHA) is a rare disorder characterized by the presence of autoantibodies against coagulation factor VIII (FVIII) 2, 3.
- The incidence of AHA is approximately 1 per million per year, with a high mortality rate of more than 20% 2.
- AHA may be associated with various conditions, including pregnancy, autoimmune diseases, malignancy, infections, or medication, but approximately 50% of cases remain idiopathic 2, 4.
Possible Aetiologies
- Autoimmune disorders, such as rheumatoid arthritis or lupus, may be associated with AHA 2, 4.
- Malignancies, including lymphoma or cancer, may also be linked to AHA 2, 4.
- Infections, such as HIV or hepatitis, may trigger the development of AHA 4.
- Medications, including penicillin or sulfa drugs, may also be associated with AHA 2.
Mechanisms
- The autoantibodies against FVIII neutralize its procoagulant function, resulting in severe bleeding complications 2, 3.
- The diagnosis of AHA is based on the isolated prolongation of activated partial thromboplastin time (APTT) and reduced FVIII levels 2, 3.
- Treatment of AHA involves two aspects: eradication of antibodies and maintenance of effective hemostasis during bleeding episodes 2, 3.
- Bypassing agents, such as recombinant activated factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC), are used to control acute bleeding episodes 3, 5.
- Immunosuppressive therapy, including corticosteroids, cyclophosphamide, and rituximab, is used to eradicate the autoantibodies 2, 3, 6.
Low Fibrinogen Activity
- There is limited information available on the specific relationship between acquired haemophilia A and low fibrinogen activity.
- However, it is known that fibrinogen plays a crucial role in blood coagulation, and low fibrinogen levels can increase the risk of bleeding complications 6.
- Further research is needed to fully understand the relationship between acquired haemophilia A and low fibrinogen activity.