In a study published in Cureus, Sharathkumar and Mokdad labeled acquired hemophilia A as an “ultra-rare autoimmune disorder” of which nonhemophilia experts have “limited awareness.”
Clinicians are generally more well-versed in congenital hemophilia A, an X-linked disorder that predominantly affects males. Acquired hemophilia A bears hallmarks similar to congenital hemophilia A (instead of a lack of factor VIII [FVIII], patients with the congenital disorder develop inhibitors to FVIII activity, with similar results), but differs in that it is more prevalent among older patients, with most individuals diagnosed with this condition 70 years of age or older. Another manifestation is also seen in women of childbearing age (median age, 33.9 years).
Acquired hemophilia A also affects males and females in equal measure, as it is not linked to the X chromosome. Epidemiologists estimate that acquired hemophilia A has an incidence of 1 case per million individuals annually, which might itself be an underestimation. The extraordinary rarity of this condition presents a significant impediment to timely diagnosis, contributing to mortality in up to 1 in 3 individuals.
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What Causes Acquired Hemophilia A?
Regarding the etiology of acquired hemophilia A, around half of all cases are considered idiopathic; the remaining half is associated with other disorders such as autoimmune diseases and malignancies. Either way, patients with acquired hemophilia A are likely to first present to a nonhemophilia expert, such as their primary care physician. Studies have demonstrated a less than satisfactory understanding of this condition among physicians across various disciplines, including emergency care clinicians, surgeons, and rheumatologists.
Read more about hemophilia etiology
The main similarity of this disorder with congenital hemophilia is that it typically presents as unexplained joint and/or muscle bleeds. Bleeding in other parts of the body, such as in the gastrointestinal, genitourinary, and retroperitoneal spaces have also been noted. These bleeding episodes can be fatal; studies suggest an overall mortality rate of close to 20%.
“Clinicians must maintain a high index of suspicion for this diagnosis in adult patients with new onset of bruising or bleeding with a prolonged partial thromboplastin time (aPTT),” Pishko and Doshi wrote in the Journal of Blood Medicine. “Diagnostic delays may result from lack of awareness due to the rarity of acquired hemophilia A and the need for centers to send out the laboratory work-up to a reference laboratory.”
Indeed, the greatest danger in the consultation room is that clinical suspicion is not raised in the slightest; this means that the condition is likely to remain undiagnosed until it is revisited once spontaneous bleeding occurs again. Hemophilia experts have recognized the likelihood of this scenario playing out in clinical centers across the country and have attempted to develop a diagnostic algorithm to help guide physicians to conduct direct testing when appropriate.
This diagnostic algorithm as outlined by Pishko and Doshi is based on a few key principles. First, clinical suspicion for acquired hemophilia A should be raised in the event that a patient presents with spontaneous bleeding in the absence of prior personal or family history. Physicians should then order aPTT and prothrombin time tests.
Read more about differential diagnosis for hemophilia
“Acquired hemophilia A patients will have an isolated prolonged aPTT, and initial screening with a 1:1 mixing study with normal pooled plasma does not correct the prolonged clotting time,” Pishko and Doshi wrote. “Interfering substances (eg, heparins) and lupus anticoagulants must be ruled out and FVIII activity assessed. FVIII activity is <1% in approximately 50% of cases and less than 5% in 75% of cases.”
Much is still unknown about the etiology of acquired hemophilia A: for example, what triggers the spontaneous production of neutralizing antibodies to FVIII, seemingly out of the blue? What is its connection to congenital hemophilia A? In patients with no comorbidities, what if anything drives the pathophysiology of this disorder?
Managing Acquired Hemophilia A
It is important to emphasize that, as clinicians, we do not need to possess a thorough understanding of the etiology of the disease to treat it. Given the rarity of this disorder, it will some time before we have a complete grasp of how this disease develops.
“The initial management of acquired hemophilia A can be broken down into two parts: obtaining and maintaining hemostasis and re-establishing FVIII immune tolerance by eradicating the inhibitor,” according to Pishko and Doshi.
The first part of this management strategy is to stop acute bleeding by using a bypassing agent or recombinant porcine sequence FVIII. Studies indicate that human-derived recombinant FVIII products and desmopressin are generally ineffective. Physicians treating signs of acute bleeding should keep a close eye on hemoglobin levels and make a clinical decision on the need for transfusions. Clinicians should not be overly enthusiastic in managing bleeds to the point that the risk of thrombosis occurs.
Read more about hemophilia treatment
The second strategy is to eliminate inhibitors by using immunosuppressive therapies such as corticosteroids or a mixture of rituximab/cyclophosphamide. It usually takes 5 to 6 weeks for inhibitors to be eliminated via immunosuppression. However, it should be noted that approximately one-third of patients may achieve spontaneous remission without immunosuppressive therapies; hence, physician discretion is always needed.
“Although rare, acquired hemophilia A carries a high risk of morbidity and mortality and requires prompt treatment,” Pishko and Doshi concluded. “Additional prospective studies are necessary to determine the optimal management and identify biomarkers of response that can inform therapeutic decisions.”
References
Sharathkumar A, Mokdad AG. Review of potential barriers to effective hemostatic management of acquired hemophilia A by non-hemophilia experts in the United States. Cureus. 2023;15(1):e33927. doi:10.7759/cureus.33927
Pishko AM, Doshi BS. Acquired hemophilia A: current guidance and experience from clinical practice. J Blood Med. 2022;13:255-265. doi:10.2147/JBM.S284804
