Delayed diagnosis common in AHA, affecting 1 in 3 patients: Study
Acquired hemophilia A finding often takes over 1 month from first bleed
A delayed diagnosis is common for people with acquired hemophilia A (AHA), according to a new study that found that it took more than a month to get a diagnosis after the first bleeding episode for about 1 in 3 patients.
Despite these delays, all AHA patients in the study achieved remission after receiving treatments to stop bleeding and suppress the immune system, the data showed.
Still, “this study demonstrates that a … [specialized care center] can effectively manage patients with AHA,” the researchers wrote.
Further, diagnostic delays could be “mitigated by disseminating educational materials in a straightforward format to facilitate the recognition of AHA,” the team wrote.
Their study, “The Role of the Hemostasis and Thrombosis Unit in the Management of the Patients with Acquired Hemophilia,” was published in the Turkish Journal of Hematology.
Investigating the mechanisms underlying acquired hemophilia A
AHA is a rare type of hemophilia marked by the production of self-reactive antibodies, called autoantibodies, that mistakenly attack factor VIII (FVIII), an essential blood-clotting protein. In people without hemophilia, FVIII activity typically ranges from 50% to 150%. In mild cases, it ranges between 5% and 40%, while in moderate hemophilia A it ranges from 1% to 5%. In severe hemophilia A, FVIII activity drops to less than 1%.
As with inherited forms of hemophilia, people with AHA are at risk of spontaneous or excessive bleeding episodes; in some cases, bleeds can be severe and life-threatening.
In about half of AHA cases, autoantibodies against FVIII appear without an identifiable cause, and thus are called idiopathic. In the other half, meanwhile, these autoantibodies may be associated with other autoimmune diseases, or with the postpartum period (the period following childbirth), cancers, infections, or the use of certain medications.
To further understand the mechanisms underlying AHA, a research team in Italy investigated clinical and lab data, treatment strategies, and patient outcomes of 41 people with the condition. The patients, comprising 22 women and 19 men, ranged in age from 15 to 93, and were diagnosed at a clinic between 2005 and 2023.
Among them, 10 (24%) had idiopathic AHA. A total of 18 (44%) had autoimmune diseases, while nine (22%) had an underlying cancer, and four (10%) were postpartum. Blood tests showed no significant correlation between the levels of FVIII and anti-FVIII autoantibodies.
For slightly more than one-third of patients — 15 or 36.5% — the median time from the first bleeding episode to diagnosis was more than 30 days. About half (54%) were diagnosed between seven and 30 days after bleeding onset, and four of the patients (10%) received a diagnosis within one week. All patients had active bleeding at diagnosis, with spontaneous bleeding in nearly all cases (93%).
Muscle bleeds were the most common event, seen in 61% of patients, followed by mucocutaneous bleeding — which includes the skin and mucus membranes, such as the mouth and nose — experienced by 56%. Four patients experienced postpartum bleeding, and three had blood-filled skin blisters known as hemorrhagic bullae. One patient (2.4%) had a blood clot in a vein in the leg/behind the knee during the first seven days of hospitalization, with a peak FVIII activity of 3%.
Researchers call for better education to prevent delayed diagnosis of AHA
Bleeds were managed depending on the type and severity of the bleeding. To stop acute bleeding, patients were treated with activated prothrombin complex concentrate and/or recombinant human-activated factor VII. Tranexamic acid, sold in the U.S. as Cyklokapron, was also used for mucocutaneous bleeding and as an add-on treatment in all patients.
Six patients had been receiving antiplatelet medications to prevent blood clotting due to a history of clotting events, particularly heart disease. When peak FVIII activity rose to more than 30% with anti-bleed treatment, preventative anti-blood clotting drugs were restarted.
Steroids were the most frequently used immunosuppressive agent, particularly in combination with cyclophosphamide. Rituximab, a type of antibody therapy, was combined with other immunosuppressive agents, including steroids, and was the second choice for two patients. Those who didn’t respond to a combination of steroids and cyclophosphamide were treated with either immunoglobulins (12%) or methotrexate (2.4%). Plasma exchange therapy, or plasmapheresis, was used for 7% of the patients.
No patient died in the hospital, and clinical remission was achieved in all cases. One patient died 20 days after discharge due to infection, and two due to cancer one month later. A year later, one patient with an autoimmune disease (polymyalgia rheumatica) had a relapse.
We observed a significant delay in diagnosis by [nonspecialized] or general practitioners, who often overlook the disease.
According to the researchers, a delayed diagnosis often occurs when patients are treated in a facility without a specialized care center or with clinicians not trained specifically to look for AHA.
“We observed a significant delay in diagnosis by [nonspecialized] or general practitioners, who often overlook the disease,” the researchers concluded.
In this study, no patient died, the team reported — noting that this likely was “because the management of the disease was conducted in a [specialized] unit equipped with a clinical ward, a [specialized] laboratory, and a dedicated ambulatory service.”
Better education for clinicians and the creation of specialized patient care centers are “essential” for better managing AHA, the team noted.
“This is crucial for optimal patient care,” the researchers wrote.
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