Case Presentation: A 74 year old male with a history of atrial fibrillation on rivaroxaban was admitted to an outside hospital with a spontaneous right gluteus medius and piriformis intramuscular hematoma measuring 5.8 cm found on computerized tomography (CT). On admission, he had a hemoglobin of 7.7 gm/dL, an elevated activated partial thromboplastin time not corrected with mixing studies, and a depressed activity of factor VIII (FVIII) with inhibitor of 35 Bethesda units (BU), consistent with acquired hemophilia A (AHA). Of note, one month prior to admission, the patient presented to an outpatient clinic with symptomatic anemia, low ferritin, and low vitamin B12. Colonoscopy, upper endoscopy, and M2A capsule endoscopy were negative for a source of overt or occult bleeding. The patient was taken off NSAIDs and rivaroxaban, started on a double dose of proton pump inhibitor, and given transfusions of red blood cells, IV ferric gluconate, and iron and B12 supplements. On transfer to our hospital for further management of AHA, the patient was hemodynamically stable. The patient was given recombinant porcine FVIII (rpFVIII) IV 100 units/kg twice, switched to recombinant FVII activated (rFVIIa) 90mcg/kg every 4 hours, then transitioned to activated prothrombin complex concentrate (APCC) 5000 units every 8 hours for 2 weeks. He was started on prednisone 1mg/kg daily and discharged on a taper, starting with 100mg daily. He was given the first of 4 doses of rituximab 375 mg/m2. 1.5 weeks after discharge, he was readmitted with a rebleed and a right gluteus musculature hematoma measuring up to 20.2 cm on CT. He was first given rFVIIa to control bleeding, then given a rpFVIII taper. He also received his last dose of rituximab and finished the taper off prednisone. The patient showed eradication of inhibitor, recovery of FVIII activity, and no further bleeding events. His AHA is in remission.
Discussion: AHA is a rare autoimmune bleeding disorder caused by spontaneous production of autoantibodies targeting endogenous coagulation FVIII. While most cases are idiopathic, AHA can also be associated with malignancy, autoimmune disorders, pregnancy, infections, dermatologic conditions, and certain medications. Greater than 94% of AHA patients present initially with a bleeding event, subcutaneous bleeding accounting for greater than 80% of these cases. AHA clinical research is hampered by the rarity of the disease and current clinical guidelines for AHA treatment are primarily based off of observational findings from international registries. Management of AHA should be focused on the following three goals: controlling and preventing bleeding, eradication of the inhibitor, and treatment of underlying disease. To control bleeding, first-line hemostatic agents in AHA include rpFVIII, rFVIIa, and APCC. All adult patients with AHA should have immunosuppressive therapy to eradicate inhibitors. Corticosteroids alone for 3−4 weeks are first-line for patients with FVIII ≥1 IU/dL and inhibitor titer ≤20 BU at baseline. Corticosteroids and rituximab are considered first-line for inhibitor eradication in patients with FVIII <1 IU/dL or inhibitor titer >20 BU.
Conclusions: Initial assessment, diagnosis, and management of AHA patients are often completed by emergency medicine and internal medicine physicians. AHA patients are at high risk for morbidity and mortality. Therefore, understanding when to assess for and how to manage AHA will allow for earlier detection and initiation of correct treatment.