Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII (FVIII), and the disorder is understudied given its rarity and the lack of randomized prospective trials to guide therapy.
The combination of rituximab and emicizumab can be an effective and safe regimen for the treatment of acquired hemophilia A, according to a poster presented at the 62nd American Society of Hematology Annual Meeting and Exposition.
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII (FVIII), and the disorder is understudied given its rarity and the lack of randomized prospective trials to guide therapy. In practice, treatment involves attaining hemostasis and eliminating the FVIII inhibitor, typically with high-dose steroids and either cyclophosphamide or rituximab. However, current approaches carry risk of significant adverse events and delayed or inadequate responses.
Emicizumab is a bispecific antibody that targets coagulation factors IXa and X to recapitulate the function of endogenous FVIII, according to the study authors. The objective of the study was to present a case series of patients with acquired hemophilia A who were successfully treated with a regimen consisting of rituximab and emicizumab.
Patients older than 18 years of age who were diagnosed with acquired hemophilia A were identified and received treatment with rituximab and emicizumab at Brigham and Women’s Hospital between 2019 and 2020. The researchers performed a retrospective chart review, and the data collected included the patients’ clinical presentation, laboratory studies, and treatments received.
Further, the team recorded the time to normalization of the activated partial thromboplastin (aPTT) time and chromogenic FVIII activity following emicizumab and rituximab initiation, respectively. Activated prothrombin complex concentrate was avoided given the use of emicizumab.
The study included 8 patients with acquired hemophilia A who received treatment with emicizumab and rituximab, with a median age of 81 years. All patients sought medical attention for extensive ecchymoses or bleeding and were found to have prolonged aPTT leading to FVIII inhibitor identification. Additionally, patients concurrently received 4 weekly doses of rituximab 375 mg/m2 and 4 weekly loading doses of emicizumab 3 mg/kg, according to the study authors.
Patient 1 continued emicizumab 3 mg/kg every 2 weeks to complete 3 months of treatment, whereas patients 2, 3, and 8 received high-dose prednisone (1 mg/kg) at the start of treatment for a range of 10 to 14 days. Patient 8 received 7 additional days of prednisone for an initial aPTT of 60.7 seconds before starting emicizumab and rituximab, with no clinical response when treated with prednisone alone.
Patients 2, 5, and 7 required vascular embolization, according to the study authors. Further, patients 2 through 8 had aPTT retested within 1 week of starting emicizumab and the aPTT for these patients normalized within 10 days of starting emicizumab. Other than patient 5, who had recurrent hematuria from a persistent anatomic bladder defect that eventually required prostatic artery embolization, patients did not require rFVIIa or red blood cell (RBC) transfusions for more than 7 days after starting emicizumab. Patient 5 required 28 doses of rFVIIIa and 3 units of RBC transfusions after starting emicizumab, the median number of rFVIIa doses and RBC units given to the remaining 7 patients was 0 and 0, respectively.
Further, patients 2 and 3 had chromogenic FVIII levels obtained more than 30 days after starting rituximab with improvement in FVIII activity to 29% and 86%, respectively. During a median follow-up of 102 days, no patients experienced recurrent bleeding. However, patient 3 exhibited a slowly increasing aPTT that reached 46.3 seconds on day 233 of follow-up without symptoms, with further diagnostic testing still pending.
The study authors concluded no thrombotic events or thrombotic microangiopathy occurred. The treatment with weekly emicizumab led to aPTT normalization after 1 to 2 doses and facilitated hemostasis, as reflected by a median usage of 0 rFVIIA doses and 0 RBC transfusions after starting emicizumab when excluding 1 patient with hematuria from an anatomic defect.
These results compare favorably to historical reports. Although no patients have had recurrent bleeding, additional chromogenic FVIII activity testing for patients is needed to confirm long-term normalization of FVIII activity.
Chen EC, Gibson WJ, Temoczko P, et al. Treatment of acquired hemophilia A with rituximab and emicizumab. Poster presented at 62nd American Society of Hematology Annual Meeting and Exposition. Published December 5, 2020. Accessed December 8, 2020.