Virginia Research Day 2021

Medical Resident Research Case Reports

20 Acquired Hemophilia A with a Possible Genetic Component

Linsey Atchison, DO; Akintunde Akinleye, MD Corresponding author: michael.moore1@LPNT.net

SOVAH Health Internal Medicine Residency Program

Context: Acquired Hemophilia A (AHA) is a rare spontaneous bleeding disorder caused by autoantibodies to clotting factor VIII. It can cause life-threatening bleeding with soft tissue bleeding being common. While this rare condition has been associated with pregnancy, autoimmune diseases, and various medications, the majority are classified as ‘idiopathic’. Case Report: A 59-year-old Caucasian female who presented to the Emergency Room with extensive acute, non-traumatic right upper extremity and bilateral lower extremity bruising and low hematocrit was admitted. Six weeks prior, she was hospitalized for a possible pulmonary embolism and started on apixaban. One week prior, she was admitted for a hypopharyngeal hematoma when apixaban was stopped. Family History (Hx): Hypertension but no blood or bleeding disorders. Past Med Hx: Hypertension, chronic obstructive pulmonary disease, coronary artery disease with stents. Outpatient Meds: Allopurinol 100 mg, amlodipine 5 mg, colchicine 0.6 mg, prednisone 10 mg, & omeprazole 40 mg each daily, ferrous sulfate

325 mg and metoprolol tartrate 25 mg each twice a day, and acetaminophen 650 mg Q6H PRN. Social Hx: Daily cigarettes and beer; cocaine use 1-2/month. Pertinent Review Systems: Dysphagia from pharyngeal hematoma, bilateral leg pain, & large, hard, painful nodules/ecchymoses on legs. Pertinent Physical Exam: Vital Signs: Temp 98.8 F, Bp 126/71, pulse 104, respirations 18, SpO2 of 99% on room air, large tender right upper medial arm and right inner thigh bruising and a firm soft tissue mass from her left buttock to posterior thigh. Pertinent Labs: WBC 25,000, hemoglobin 8.5, MCV 79.3, platelets 593 K, PTT 13.3, INR 1.2, APTT > 200 (7 days after apixaban). Treatment: Intravenous saline and serial blood counts were begun. Hematology consult recommended: PTT 1:1 mixing study at 51, incubated PTT 1:1 mixing study at 85, and factor VIII activity < 1. With a presumptive diagnosis of AHA, she was transferred to a tertiary care center for management. Further testing there demonstrated a high porcine factor VIII inhibitor of 12 (≤ 0.3 normal) and a high

factor VIII inhibitor titer of 653BU (>10BU = high titer). Genetic testing found a 50% ASXL1 c.1898A>G (p.H633R) missense mutation at the genomic position chr20: g.31022413A>G. The high factor VIII inhibitor titer level and continued bleeding necessitated prednisone, cyclophosphamide, antihemophilic factor, anti-inhibitor coagulant complex (FEIBA), rituximab, 7 units of RBCs, and 3 units of FFP. Comment: Acquired hemophilia A, a very rare form of hemophilia, is estimated to affect approximately 1-4/1,000,000 people yearly. Most cases are thought to be idiopathic, but several conditions and medications have been associated with acquiring this rare bleeding disorder. This case presents a possible, previously unidentified, contributing factor: ASXL1 gene mutations. While ASXL1 mutations are most often identified in myelodysplastic syndromes and myeloid malignancies, this case could spark new research into ASXL1 mutations as a possible genetic factor associated with the development of AHA.

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