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 NegativeCOVID-19 *Parvovirus B19 IgG IgM

CMV IgG IgMEBV *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