Acquired hemophilia A is a hemorrhagic disorder caused by autoantibodies attacking coagulation factor VIII (FVIII). It is a rare but potentially lethal disorder.
Unlike congenital hemophilia, acquired hemophilia A is characterized by the sudden appearance of autoantibodies that neutralize FVIII at a later age. Epidemiological studies indicate that it typically occurs in patients aged more than 60 years. There is also a notable incidence among postpartum females. Pediatric cases are exceedingly rare.
Approximately half of the cases of acquired hemophilia A are idiopathic; the rest are associated with various conditions, such as cancer, infection, pregnancy, autoimmune disorders, and certain drugs.
Read more about hemophilia etiology
Aside from the age of onset, acquired hemophilia A also differs from congenital hemophilia on one important point: bleeding tendency. In congenital hemophilia, spontaneous bleeding into the joints is typically observed; in acquired hemophilia A, the most common types of bleeding are mucosal hemorrhages and massive subcutaneous blood extravasations. Intracranial hemorrhage is rare, but often fatal if it occurs.
A Case of Postpartum Acquired Hemophilia A
In The Egyptian Journal of Internal Medicine, El Demerdash and colleagues presented a case study of a 32-year-old, G2P1 female who presented to the obstetric department for the purpose of normal vaginal delivery. She experienced excessive vaginal bleeding during her puerperium and her hemoglobin fell from 11 g/dL to 6.8 g/dL. A hysterectomy was performed. However, her condition continued to deteriorate and she was referred to the intensive care unit with a diagnosis of disseminated intravascular coagulation (DIC).
Laboratory workup revealed the following results:
- Platelet count: 262,000 mm3 (normal: 130-400 mm3)
- Activated partial thromboplastin time (aPTT): 68.4 s (normal: 25.1-34.7 s)
- Fibrin degradation product (FDP): 20 mg/L (normal: <10mg/L)
- D-dimer: 1 μg/mL (normal: <0.5 μg/mL).
Her physicians decided that a diagnosis of DIC was unconvincing. Additional laboratory tests revealed the following:
- aPTT mixing studies: 67 s (normal: 25.1-34.7 s)
- FVIII rate: 4% (normal: 70%-150%)
- FVIII inhibitor level: 10 BU (normal: <0.6 BU)
- FIX rate: 103.9% (normal: 70-120%)
- von Willebrand factor: 89.5% (normal: 50-160%).
Following these results, the patient was diagnosed with postpartum acquired hemophilia A.
Her physicians attempted to stop her bleeding by prescribing rFVIIa. Prednisolone was then added to eradicate inhibitors. Her condition began to improve and she only displayed intermittent symptoms and prolongation of aPTT. Rituximab was then added, and a resolution of inhibitors was achieved after 3 weeks.
Detecting Acquired Hemophilia A
Overall, acquired hemophilia A is an underdiagnosed and hence undermanaged condition. This is due to a few key factors. One of them is that this condition often presents in elderly patients, and elderly patients are at higher risk of having comorbidities, including other blood disorders, making acquired hemophilia A easier to miss. (This is a problem in diagnosing any disorder that presents itself at a later age with conditions that could plausibly be linked to other existing comorbidities.)
Another factor driving the underdiagnosis of acquired hemophilia A is a poor understanding of this disease, or a lack of knowledge of it altogether. Virtually all healthcare professionals would be aware of congenital hemophilia; the same cannot be said about acquired hemophilia. As a very rare disorder, it may not provoke clinical suspicion when symptoms appear.
In the American Journal of Hematology, Kruse-Jarres and colleagues listed 2 situations in which a diagnosis of acquired hemophilia A should be suspected:
- Patients with a recent onset of abnormal bleeding with an isolated prolonged aPTT and normal prothrombin time (PT), especially in the elderly and peripartum and postpartum women.
- A nonbleeding patient with an isolated prolonged aPTT, a mixing study consistent with an inhibitor, and a negative lupus anticoagulant, despite not being on anticoagulation therapy.
If acquired hemophilia A is suspected, then a full laboratory hemophilia workup should commence.
Principles of Managing Hemophilia A
In managing a patient with acquired hemophilia A, a few principles are to be considered. First is the control and prevention of any significant bleeding. Patients with acquired hemophilia A may not present with an acute bleeding episode during the time of diagnosis, in which case hemostatic control is not an urgent need. However, excessive bleeding, such as in the case of the patient in the case study, should be adequately addressed.
Read more about hemophilia treatment
Secondly, physicians should aim to eradicate inhibitors by the use of immunosuppressants. This can be in the form of corticosteroids alone (prednisolone being preferred), or corticosteroids plus rituximab or cytotoxic agents. Third is the treatment of any underlying disorder that physicians suspect may have contributed to the patient’s acquired hemophilia A.
“Management of [acquired hemophilia A] is representing a medical challenge from its diagnosis to its treatment,“ El Demerdash and colleagues wrote. ”The only parameter that differed between patients who responded to treatment and those who did not was a delay in time to treatment.”
By being aware of the possible signs and symptoms of acquired hemophilia A, physicians will be better equipped to diagnose this disease in a timely manner and take immediate action to prevent further patient deterioration.
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
Kruse-Jarres R, Kempton CL, Baudo F, et al. Acquired hemophilia A: updated review of evidence and treatment guidance. Am J Hematol. 2017;92(7):695-705. doi:10.1002/ajh.24777