Infection is top killer in acquired hemophilia A, study finds
Registry study finds more than 50% of deaths related to infection
Infection and related complications pose a serious risk to people with acquired hemophilia A (AHA), accounting for more than half of the deaths in a registry study in Spain.
About 15% of participants in the study experienced at least one infection requiring treatment or hospitalization, the study found. About two-thirds of these were fatal.
The researchers said the findings were likely related to the immunosuppressant effects of AHA treatments, and preventive treatment (prophylaxis) against common microbes could reduce the risk.
The study, “Infectious complications in acquired haemophilia A: Insights from the Spanish Registry (AHASR),” was published in Haematologica.
In hemophilia, blood cannot properly form clots. This leads to excessive bleeding, the hallmark hemophilia symptom. Most people with hemophilia have genetic mutations that affect the production or function of one of the clotting proteins involved in the process.
Acquired hemophilia and immunosuppressants
Hemophilia isn’t always genetic. It sometimes arises due to immune attacks directed against the same group of clotting proteins. This is called acquired hemophilia, and is often related to an underlying disease or precipitating incident.
In AHA, a form of acquired hemophilia, immune attacks target FVIII, the same clotting protein affected by genetic mutations in hemophilia A.
In addition to therapies that help keep bleeding under control, people with AHA may receive immunosuppressants to eliminate the antibodies driving the immune attacks against FVIII. An immunosuppressive regimen might include a combination of steroids, the chemotherapy agent cyclophosphamide (sold as Cytoxan), and rituximab (sold as Rituxan and others).
However, these immunosuppressive treatments also make the body more susceptible to infections.
“Therefore, early recognition, infection control measures, and appropriate antimicrobial therapy are crucial in managing these cases,” the researchers wrote.
The investigators examined the frequency of infections in a Spanish registry of individuals with AHA, which includes data from patients diagnosed at 36 Spanish hospitals from May 2014 to December 2024.
The study involved 257 patients, with a median age of 73.5. Most (89%) had clinically relevant bleeds at the time of diagnosis.
Most participants (91.2%) received immunosuppressive treatment to eliminate antibodies. Steroids with cyclophosphamide was the most common regimen (42.7%), followed by steroids alone (26.5%), and rituximab regimens (15.8%). Treatment with steroids alone became significantly more common after a change in international treatment guidelines in 2020.
Over a median follow-up of 135 weeks (just over 2.5 years), about one-quarter of participants died. Infections were the most common cause of death, accounting for 51.6% of cases.
A total of 46 infections were reported in 40 participants. Just over one quarter of these received antimicrobial prophylactic treatment with antibiotics and/or antifungal medications.
There were no significant differences in risk of infection or infection-related mortality across immunosuppressant regimens. Infection-related mortality rates were also similar regardless of whether participants received prophylactic treatment against potential infections.
Registry data included information about infection-causing microbes in 31 of the 46 recorded infections requiring treatment or hospitalization. Most of these were bacteria, primarily belonging to a group of rod-shaped bacteria called gram-negative bacilli. In three cases, the COVID-19 virus was identified as the root cause. Aspergillus, a genus of mold species, accounted for one other infection.
In just over half of the cases, infections affected the lungs, causing pneumonia. In about a third, infected patients developed sepsis, an overwhelming response to infection that can lead to organ damage and failure.
Limiting reliance on immunosuppressants, particularly steroids, may be a good way to reduce infection risk when possible, the researchers wrote.
“Treatment must be individualized to minimize steroid exposure, introducing combined therapy as early as possible in low-risk patients if there is no favourable clinical response,” they wrote.
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