Acquired hemophilia A associated with amlodipine use in a hypertensive patient: A case report Free

Hemophilia is a bleeding disorder characterized by deficiency of factors within the coagulation cascade. Typically, hemophilia is a genetic disorder, however under certain circumstances patient can develop acquired hemophilia. Acquired Hemophilia A (AHA) is a rare autoimmune disorder where autoantibodies target coagulation factor VIII (FVIII) by interfering with the function of FVIII or increased clearance of FVIII which lead to severe bleeding. With an incidence of about 1.5 cases per million annually, AHA can be linked to malignancies, autoimmune diseases, and, less commonly, medications.

A 52-year-old male with hypertension on amlodipine and prior immune thrombocytopenia purpura secondary to dupilumab presented as transfer for upper and lower extremity swelling with anemia. At outside hospital, laboratory findings were significant for hemoglobin/hematocrit of 8.5 g/dL/26% with baseline around 12 g/dL/36%. Ultrasound of the extremities demonstrated no deep venous thrombi. Computed tomography of his extremities revealed intramuscular hematomas with concern for were concerning for evolving compartment syndrome. Extensive hematological work-up was ordered at that time including ADAMTS13 antibody, serum electrophoresis, haptoglobin, lactate dehydrogenase, von Willebrand antigen, PT/INR, reticulocyte count, iron profile with ferritin, vitamin B12, folate, and peripheral blood smear (PBS). Of which, none demonstrated any significant finding aside from normocytic anemia on PBS. While at outside hospital, his anemia continued to worsen with patient receiving blood products. The primary team spoke with our in-house hematology/oncologist with transfer to our facility. Upon transfer, general surgery was consulted given concern for compartment syndrome however no acute surgical intervention was necessary. Hematology/oncology further ordered factors VIII, IX, XI, XIII, V, platelet function analysis, thrombin time, FVIII inhibitor level, and ANA with FVIII found to be extremely low, FVIII inhibitor level to be extremely elevated, and ANA positive. Literature review noted amlodipine as a rare potential cause of AHA prompting its discontinuation. He was started on rituximab, glucocorticoids, cyclophosphamide, and factor VIII inhibitor bypassing activity for his AHA. During hospital course aPTT was 72 seconds and at time of discharge was within normal limits. He was then discharged on prednisone, cyclophosphamide, with further rituximab infusions in the outpatient setting. Outpatient rheumatology stated patient had no underlying autoimmune condition that was responsible for his AHA.

A high index of suspicion is crucial for diagnosing AHA. When evaluating patients with suspected bleeding disorders, it is essential to evaluate PT, aPTT, mixing studies, platelet count, fibrinogen, coagulation factor levels, inhibitor assay, PBS, and possible autoimmune etiologies. In those with AHA, prolonged aPTT is noted and does not correct with normal plasma during a mixing study. When FVIII is reduced, one must rule out underlying conditions that can cause acquired hemophilia A such as malignancy, autoimmune diseases, connective tissue disorders, or medications. In the case of our patient, his work-up was unremarkable for other causes – except with his history of amlodipine. Given the presentation of the case, this was likely cause of his AHA.. It is essential to have a thorough work-up and history to evaluate hemophilia and to discern what steps are needed next in the care of the patient .