Deciphering Paroxysmal Nocturnal Hemoglobinuria: An Unusual Paradigm of Hemolytic Anemia

Paroxysmal nocturnal hemoglobinuria (PNH), a clonal hematopoietic stem cell disorder, arises from the increased sensitivity of red blood cells (RBC) to complement due to an acquired deficiency of certain glycosylphosphatidylinositol (GPI)-linked proteins, resulting in chronic intravascular hemolysis, arterial and venous thrombotic phenomena, multi-organ damage, and failure. We present an intriguing case of hemolytic anemia, initially suspected to be drug-induced, and later found to be associated with PNH, despite being a subclinical clone. A clinician should not hesitate to repeat fluorescent-labeled aerolysin (FLAER) cytometry if the clinical picture strongly favors a diagnosis of PNH. This case marks the importance of testing for PNH clones in autoimmune hemolytic anemia (AIHA) since their prevalence is not negligible and may correspond to a prominent hemolytic pattern, a higher thrombotic risk, and a higher therapeutic indication, such as eculizumab. This underscores the significance of conducting a thorough evaluation for occult causes of treatment-unresponsive hemolytic anemia, paving options for an early and alternative therapeutic approach.