FEVERS AND FATIGUE: A Case of Paroxysmal Nocturnal Hemoglobinuria in the Setting of Aplastic Anemia Julia Kostka, MD, Sylvester Dorobisz, MD, Faisal Al Bahrani MD, David J Regelmann, MD Department of Medicine, St Vincent’s Medical Center Bridgeport, CT Background • Fever in the setting of pancytopenia has a wide range of etiologies, including PNH, HIV, CMV, malignancy, autoimmunity and HLH. • PNH occurs with aplastic anemia in up to 25% of patients. Case • A 21-year-old man presented with a month’s history of fatigue and a week of fevers, chills, and sore throat. • He had no known past medical history. • He moved to the US from Haiti and was sexually active. • He was found to be febrile with labs significant for leukocytes 1600/mcl, hemoglobin 3.5 gm/dL and platelets 4000/mcl. Neutrophil count was 400/mcl • He was started on cefepime, vancomycin, acyclovir and fluconazole and blood was transfused. • His fevers improved with antibiotics, but no clear source of infection was identified. Multiple studies were sent, including COVID-19 testing, ANA, SPEP/UPEP, HIV, hepatitis serologies, EBV IgG, and parvovirus IgM/IgG. • Bone marrow biopsy was performed and showed hypocellular marrow, consistent with aplastic anemia (AA). Flow cytometry showed evidence of paroxysmal nocturnal hemoglobinuria (PNH) clone. References Discussion • AA is closely related to PNH, and approximately 20% of patients with AA also have PNH at diagnosis. • While PNH can occur in patients with acquired AA, it rarely occurs in patients with inherited AA. • The mechanism of PNH in patients with AA is thought to be due to autoimmune effects that can target hematopoietic stem cells and possibly GPI anchors. • The abnormal blood cells are thought to initiate an immune response that damages hematopoietic stem cells and other hematopoietic precursors. • Patients benefit from PNH testing when AA suspected because the presence of PNH cells is associated with a superior response to immunotherapy. • Maciejewski, J. P., Rivera, C., Kook, H., Dunn, D., & Young, N. S. (2001). Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. British Journal of Haematology,115(4), 1015- 1022. • Bart Lee Scott. David Dingli,,M. Atef Shrit,. (2018). Clinical Consequences of Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia: A Multidisciplinary Discussion. Clinical Advances in Hematology and Oncology. 16(4), 11. Positive Negative COVID-19 * Parvovirus B19 IgG IgM CMV IgG IgM EBV * HIV * SPEP/UPEP * ANA * Hepatitis Panel * GPI anchors, CD55 and CD59 Figure A) A representation of the mechanism of PNH. Phosphatidylinositol glycan class A (PIGA) mutation leads to the absence of two glycosylphosphatidylinositol (GPI)- anchored proteins, CD55 and CD59, resulting in increased complement-mediated hemolysis of erythrocytes. A Table A) Results of patient’s tests for neutropenic fever. A