Case Presentation: A 77-year-old woman presented with altered mental status, tachycardia, tachypnea, and hypotension. Her family noted 1 month of progressive lethargy, with spontaneous subconjunctival hemorrhage and various episodes of facial and extremity bruising (for which she had 3 prior ED visits). Past medical history was notable for hypertension, remote history of nosebleeds, and menorrhagia treated with hysterectomy. She had no abnormal bleeding in prior surgeries or pregnancies, liver disease, anticoagulant use, or family history of bleeding disorder. Physical exam was notable for petechiae and ecchymosis on her tongue, soft palate, and extremities. Laboratory studies were notable for WBC 19, Hb 7.1, platelets 510, new azotemia, acidosis, and elevated inflammatory markers. CT showed a retroperitoneal hematoma. Coagulation tests revealed a normal PT and fibrinogen, but elevated aPTT (also present 1 month prior), uncorrected with a mixing study. Additional workup showed completely suppressed VIII activity and quantified factor VIII inhibition at 90 Bethesda units. Workup for infectious, malignant, and autoimmune etiologies were negative. Her clinical condition initially improved with IV hydration and pRBC transfusion, but she subsequently developed a new arm hematoma and worsening anemia. Neither pooled cryoprecipitate nor DDAVP were effective to correct the aPTT or prevent further bleeding. Ultimately, recombinant human factor VIIa (rFVIIa) was given for hemostasis. She was started on prednisone 80 mg daily in an attempt to suppress the autoantibody. She sustained another extremity soft tissue hemorrhage one week later, for which she was stabilized with pRBC transfusion and ultimately discharged to SNF on prednisone.
Discussion: Acquired hemophilia A (AHA) is the most common type of acquired coagulation factor inhibitor disorder, with an estimated U.S. incidence of 0.2-1.0 cases per million population per year, typically affecting elderly patients. Patients can develop factor VIII inhibitors in autoimmune disorders, the postpartum period, malignancy, or drug reactions; half are idiopathic. The hallmark presentation is bleeding, in the form of large hematomas, extensive ecchymoses, or severe mucosal bleeding, and is often a medical emergency. Associated mortality estimates range from 7.9-22%. Diagnosis is made by an isolated prolonged aPTT that does not correct with a mixing study, and a Bethesda assay, which quantifies the inhibiting antibody titer as well as factor VIII activity. Active bleeding should be treated with activated prothrombin complex concentrates (aPCC) or rFVIIa. The elimination of factor VIII inhibitors can be achieved in 80% of cases with corticosteroids; the addition of cyclophosphamide or rituximab has been used in refractory cases. Serial aPTT is not a reliable measure of response to therapy or risk of bleeding. Factor VIII activity and inhibitor titers should be rechecked every 2-4 weeks until Bethesda assay is negative, at which point immunosuppressive therapy may be tapered.
Conclusions: AHA is a very rare cause of spontaneous bruising and hemorrhage with significant morbidity and mortality if unrecognized but a good prognosis if treated. To ensure a timely diagnosis and prevent complications, the hospitalist must recognize an abnormal coagulation profile uncorrected by a mixing study, control hemorrhage using agents that stimulate coagulation downstream from factor VIII, and start immunosuppressive therapy to eliminate factor VIII autoantibodies.