'Separate treatment protocols needed for acquired and congenital hemophilia A'

Hemophilia A encompasses two distinct conditions. One is congenital hemophilia A, where individuals are born with a genetic predisposition to bleeding. The other is acquired hemophilia A, which develops when the body produces autoantibodies that attack normally functioning blood clotting factors.

While both are bleeding disorders caused by a factor VIII deficiency, they differ significantly in pathogenesis, clinical presentation, and treatment strategies.

“Acquired hemophilia A is a completely different disease pathophysiologically,” said Han Jae-joon, professor of hematology at Ewha Womans University Mokdong Hospital.

The bleeding patterns also differ. Congenital hemophilia A typically involves intra-articular bleeding, whereas acquired hemophilia A presents more atypically, with muscle or intra-abdominal hematomas and bleeding from the skin and mucous membranes.

The challenge, however, is that these distinctions are not fully accounted for in current diagnostic frameworks or insurance reimbursement criteria.

Due to its rarity, acquired hemophilia A is poorly recognized, increasing the risk of limited access to appropriate treatment -- especially in emergencies -- when care is guided by criteria designed for congenital cases. Antibody levels and severity thresholds are still based on those of congenital hemophilia A, which can delay timely treatment for acquired patients.

Lack of awareness and testing limitations hinder timely diagnosis

Acquired hemophilia A is often diagnosed late due to its rarity and nonspecific symptoms. Patients typically don’t suspect the condition, and healthcare providers tend to rule out more common causes of bleeding first.

Factor VIII and autoantibody tests—which are essential for diagnosis—are not routinely performed, and when they are, results can take a considerable amount of time to return. This delay often leads to missed opportunities for early intervention. In some cases, patients are only diagnosed after undergoing treatments such as blood transfusions or embolization.

Further complicating diagnosis, few hospitals are equipped to treat the condition, often necessitating patient transfers. The variability and uncertainty of clotting time tests also present barriers.

"The time to diagnosis varies widely from patient to patient, but it can take more than a month," says Dr. Jae-joon Han. "Even when the disease is identified, patients with acquired hemophilia A have neutralizing antibodies that render factor VIII ineffective, making it difficult to achieve hemostasis with standard factor VIII treatments."

Congenital vs. Acquired Hemophilia A

Congenital hemophilia A is a hereditary deficiency of factor VIII caused by a gene mutation. Patients are born with a lifelong risk of bleeding, most commonly into joints, often leading to chronic arthropathy.

Acquired hemophilia A, by contrast, results from the development of autoimmune antibodies against previously functioning factor VIII. It typically affects older adults and presents with tumor-like hematomas or atypical, unpredictable bleeding in muscles, the abdomen, mucous membranes, and other sites.

Although both conditions involve a deficiency in factor VIII, their treatment approaches differ significantly. In congenital hemophilia A, the primary strategy is to replace the missing factor VIII. However, in acquired hemophilia A, autoantibodies neutralize the administered factor, making simple replacement ineffective. As a result, treatment must focus on bypassing or suppressing the antibodies.

“Treating acquired hemophilia A is challenging for two main reasons,” Han said. “First, we must control acute bleeding quickly. Second, we need to address the underlying autoimmune response driving antibody production. Managing both aspects simultaneously is the defining therapeutic challenge of this disease.”

Limitations of bypassing agents and the emergence of Obizur

Bypassing agents remain the mainstay of treatment for acquired hemophilia A. These drugs promote hemostasis by bypassing the need for factor VIII and directly activating the coagulation cascade. Common examples include recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC).

However, bypassing agents have notable limitations. Their hemostatic effect is difficult to measure quantitatively, and they carry a risk—albeit rare—of thrombotic complications.

Obizur, a porcine-derived recombinant factor VIII, has emerged as an alternative that addresses several of these issues. Unlike human factor VIII, Obizur is less likely to be neutralized by autoantibodies, restoring clotting function even in patients with high inhibitor titers.

A key advantage of Obizur over bypassing agents is the ability to directly measure factor VIII activity. This allows clinicians to monitor treatment response and adjust dosing with precision.

“Even in patients with high antibody titers, we were able to observe immediate hemostatic effects following Obizur administration,” said Dr. Jae-joon Han. “The improved insurance coverage in Korea is a promising development, giving patients better access to this treatment option.”

‘Reimbursement criteria should move away from congenital hemophilia regulation’

The problem persists. Reimbursement criteria for treating acquired hemophilia A remain based on those for congenital hemophilia, which doesn't accurately reflect the unique needs of acquired hemophilia A patients.

For instance, access to treatment is often restricted by antibody titer levels, and severity criteria are typically based on congenital hemophilia guidelines, overlooking the actual condition of the patient. Antibody levels fluctuate over time, yet the current system prioritizes these numbers over clinical symptoms, which should take precedence.

“Applying congenital criteria to acquired patients can trigger a cascade of errors, from diagnosis to treatment,” said Dr. Jae-joon Han. “The rarer the disease, the more precise the criteria must be to accurately reflect its characteristics.”

The treatment paradigm for acquired hemophilia A has evolved significantly with the introduction of Obizur. Yet, real-world constraints limit even these innovative therapies. Reimbursement systems still revolve around congenital hemophilia, which doesn't match the needs of acquired hemophilia patients. Restrictions based on antibody titers delay timely access to treatment, and the limited availability of Obizur in hospitals often results in delays as patients transition from diagnosis to treatment.