Ultrarare Bleeding Disorder Can Strike Older Veterans

Acquired hemophilia A (AHA) is a rare, easily missed, and highly fatal blood disorder, a hematologist cautioned colleagues in a recent webinar sponsored by the Association of VA Hematology/Oncology (AVAHO). An autoimmune condition, patients with AHA develop antibodies against clotting factor VIII (F8). The incidence rate is estimated at 1 to 1.5 per 1 million per year, with a mortality rate as high as 22%.

“Hemostasis and inhibitor eradication are key pillars of treatment. But the way we do that may be changing as new therapies come online,” said hematologist Aaron Boothby, MD, of Fred Hutchinson Cancer Center and the University of Washington.

Keys to Diagnosis

Classic presentation of AHA is bruising and bleeding with an isolated elevated partial thromboplastin time (PTT), Boothby said: “Weld that onto your mind so that that isolated, elevated PTT doesn’t get missed. Because it often does.”

As for symptoms, it has a “unique bleeding pattern,” he said. It is different than congenital hemophilia, when it is common to see bleeding from the joint. That can also happen in AHA, Boothby said, but is “quite rare.” Instead, subcutaneous and intramuscular hematomas are more common.

One-half of AHA cases are idiopathic; the other half are linked to causes such as malignancy, autoimmune disease, pregnancy, infections, and skin disorders. Certain medications are culprits as well, and there have been unconfirmed signs of a link to COVID-19 vaccination.

Meet a Patient With AHA

AHA is more common in older patients, reaching its highest prevalence in patients aged ≥ 70 years, Boothby said. He highlighted the recent case of a 71-year-old male patient with diabetes, chronic obstructive pulmonary disease, and tonsillar squamous cell carcinoma.

The patient noted easy bruising and bleeding for the several months, “but hadn’t made too much of it.” He was not taking any anticoagulants or antiplatelet agents. At the emergency department, the patient’s hematomas were treated, and red blood cells were transfused. His hemoglobin level was low (6 g/dL), but no PTT test was performed, delaying diagnosis.

The patient returned with a bleeding in his knee and more hematomas. A false-positive lupus anticoagulant test initially misled the clinicians, but a high PTT test (120 seconds) ultimately led to the AHA diagnosis.

“If you’re worried about this diagnosis, don’t hesitate to reach out to your local hemophilia treatment center,” Boothby said. “We’re always available to help think through testing and management.”

Treatment: Stop Bleeding, Target Antibodies

The pillars of AHA treatment include working to stop the bleeding and eradicate inhibitors to remove the F8 antibodies, Boothby said. Recombinant porcine F8 can be used as a replacement therapy. Activated prothrombin complex concentrate and recombinant activated factor VII are bypassing therapy options.

First-line immunosuppression strategies include corticosteroids alone, corticosteroid and cyclophosphamide or mycophenolate mofetil, and corticosteroids and rituximab.

New Option Holds Promise

Boothby highlighted emicizumab, a bispecific antibody approved for congenital hemophilia being studied off label in AHA.

He cited a recent case where on of his patients was ultimately treated with recombinant coagulation factor VIIa to control the bleeding but steroids were discontinued due to concerns about wound healing and diabetes control. The patient received emicizumab and rituximab and had no bleeding at home for 3 weeks.

Boothby has no disclosures.