Acquired hemophilia A differs from classical hemophilia A in that it occurs in individuals without a previous history of bleeding. Both diseases involve neutralizing autoantibodies acting against coagulation factor VIII (FVIII). However, in acquired hemophilia A, patients typically present with an isolated prolonged activated partial thromboplastin time (aPTT) that is later discovered to be due to FVIII deficiency.
Studies indicate that 2 groups are particularly susceptible to acquired hemophilia A: pregnant women and people aged more than 60 years. Research has shown that patients who present with acquired hemophilia A typically have notable comorbidities, such as malignancy or autoimmune disease.
There is much we still do not understand about hemophilia A, largely because of its exceeding rarity. Most hemophilia research has been concentrated on congenital hemophilia, which has been increasingly well-characterized in the medical literature.
Acquired hemophilia A “treatment decisions are often based on the expertise and clinical experience of treating physicians, and referral to expert centers is often recommended to provide the best possible care,” Tiede and colleagues wrote in Haematologica.
In The Egyptian Journal of Internal Medicine, El Demerdash and colleagues published a paper that sought to chart the prevalence of acquired hemophilia A and raise awareness of this rare bleeding disorder.
The premise of this investigation is that acquired hemophilia A hardly receives any attention from the research community. There are distinct reasons why this is the case. As mentioned, elderly patients are particularly susceptible to acquired hemophilia A. However, because the elderly population tends to have other comorbidities, including ones that make bleeding more likely, physicians are sometimes quick to dismiss any new bleeding episodes as manifestations of these other comorbidities.
“It is underdiagnosed due to its rarity and unawareness of the condition when sometimes presented to surgical wards, and this may lead to delayed diagnosis and worse outcomes,” the authors of the study wrote.
Read more about hemophilia etiology
El Demerdash and colleagues presented the case study of a pregnant female patient with acquired hemophilia A. The 32-year-old woman was admitted for normal vaginal delivery. She had normal hemoglobin levels with a normal coagulation profile.
She began to experience excessive vaginal bleeding, causing her hemoglobin to drop to 6.7 g/dL. Intra-abdominal hemorrhage came into the picture, and her surgeons decided to perform a hysterectomy. Despite having no obvious obstetric cause of bleeding, the patient’s condition continued to deteriorate, and she was initially diagnosed with disseminated intravascular coagulation.
Nevertheless, blood results appeared to contradict this diagnosis: she had an isolated prolonged aPTT, normal prothrombin time, normal platelet count, and slightly elevated d-dimer and fibrin degradation products.
“Diagnosis of postpartum [acquired hemophilia A] was confirmed by doing mixing studies for aPTT which was not corrected by adding normal plasma,” the authors of the study wrote.
Her physicians prescribed her recombinant factor VIIa, as well as prednisolone to eradicate inhibitors. The patient continued to demonstrate a prolonged aPTT, meaning that inhibitors were persistently present. Rituximab was added, and inhibitors were resolved after 3 weeks of treatment.
Read more about hemophilia treatment
As demonstrated in this case study, acquired hemophilia A is typically low in the list of differential diagnoses. Therefore, patients tend to only receive appropriate treatment after significant bleeding has occurred.
“Management of [acquired hemophilia A] is representing a medical challenge from its diagnosis to its treatment,” El Demerdash et al wrote. “The only parameter that differed between patients who responded to treatment and those who did not was a delay in time to treatment.”
Preventing Breakthrough Bleeding
Studies have indicated that around 1 in 20 patients with acquired hemophilia A die from cardiovascular events such as myocardial infarction and stroke. The American Society of Hematology hence recommends that nonbleeding patients with acquired hemophilia A who have normal FVIII levels continue to be on thromboprophylaxis.
“If an indication for antiplatelet drugs or oral anticoagulants exists, the use of these drugs should be initiated after FVIII has returned to normal levels,” Tiede et al wrote.
Suffice it to say that treatment for acquired hemophilia A begins at diagnosis, proceeds to treatment, and necessitates thromboprophylaxis even after FVIII levels are normalized.
Of course, none of this would matter if acquired hemophilia A is missed altogether. Physicians should thus be aware of its most common presentation: acute bleeding episodes without a prior history of bleeding, with laboratory results showing prolonged aPTT and reduced FVIII activity. In acquired hemophilia A, subcutaneous and muscular bleeds are most commonly observed; in congenital hemophilia A, the joints are typically affected.
Once a diagnosis of acquired hemophilia A is made, patients are usually transferred to a hemophilia specialist center. Physicians then have a number of first- and second-line therapeutic options.
The bottom line is that physicians should be aware of the signs of acquired hemophilia A and take action appropriately. Excessive bleeding in patients with undiagnosed acquired hemophilia A can be lethal, and physicians should make every effort to uncover the etiology of unexplained bleeding episodes. Once a diagnosis is made, current therapeutic advancements mean that patients have a high chance of making a full recovery, with thromboprophylaxis prescribed to prevent future breakthrough bleeding.
El Demerdash DM, Ayad A, Tawfik N. Acquired hemophilia A (AHA): underreported, underdiagnosed, undertreated medical condition. Egypt J Intern Med. 2022;34(1):12. doi:10.1186/s43162-021-00074-9
Tiede A, Collins P, Knoebl P, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791-1801. doi:10.3324/haematol.2019.230771