Case Presentation: A 74 year old female with a history of atrial fibrillation presented to the emergency room due to a 1 week history of respiratory distress. She was tachypneic (respiratory rate = 24) and her room air oxygen saturation level was 91 per cent. Diminished breath sounds in the lower third of her left lung were noted, and her chest x-ray showed a moderate left pleural effusion. A chest CT scan was obtained, and it demonstrated high density organized blood products in the pleural effusion. The patient was diagnosed with a hemothorax, and this necessitated placement of a chest tube. After three days, the chest tube was removed, since there was no evidence of further bleeding.
The patient’s CBC and CMP were normal. Her prothrombin time (PT) and activated partial thromboplastin time (aPTT) were both elevated at 31 and 190.4 seconds, respectively. Her international normalized ratio was 6.7. Following the administration of fresh frozen plasma and the discontinuation of warfarin, her PT/INR normalized; however, her aPTT remained elevated. A mixing test (inhibitor screen) was done, and this showed persistent prolongation of the aPTT, which confirmed the presence of an inhibitor. The diagnosis of factor VIII inhibitor was confirmed by doing a Bethesda assay. Her Bethesda Inhibitor level was 173.0 Bethesda units (BU)/mL (normal ≤ 0.3 BU/mL). Her initial factor VIII level was 1.8 % (normal range 50 – 185 %).
Since no active bleeding was noted by hospital day number 3, it was not necessary to consider the administration of desmopressin, factor VIII concentrates, or any other appropriate therapeutic agents. In order to eliminate the factor VIII inhibitor, prednisone (1 mg/kg orally daily) and cyclophosphamide (2 mg/kg orally daily) were started. After ten days on this regimen, her factor VIII level had increased from 1.8 to 12.8%, and her aPTT had decreased from 190.4 to 77.3 seconds. The first dose of rituximab was administered on hospital day 11, and arrangements were made for her to receive additional doses in the outpatient setting. A repeat chest CT scan was done prior to her discharge (on hospital day 12), and no recurrence of the hemothorax was noted.
Discussion: Factor VIII inhibitor is the most common acquired inhibitor of coagulation. The diagnoses that are most commonly associated with acquired factor VIII inhibitors are post-partum status, autoimmune disease, and malignancy. Mucosal bleeding, substantial ecchymoses, or sizeable hematomas are often observed in patients who have factor VIII inhibitor. Hemarthroses do not typically occur in these patients. Factor VIII inhibitors cause a prolonged aPTT, and if this diagnosis is suspected, then an inhibitor screen (mixing test), should be done first. A positive inhibitor screen should be followed by a test for antiphospholipid antibodies, and if these are not present, then the Bethesda assay (confirmatory test) should be done. Limitation of bleeding and eradication of the inhibitor are the two essential features of its treatment. Glucocorticoids, cyclophosphamide, and rituximab are the medications that are most commonly used to eliminate factor VIII inhibitor, and they are usually efficacious.
Conclusions: Patients with factor VIII inhibitor may present with significant mucosal hemorrhage, ecchymosis, or hematomas. Management of factor VIII inhibitor is achieved by limiting bleeding and eradicating the inhibitor.