Paroxysmal nocturnal hemoglobinuria (PNH) is characterized primarily by hemolytic anemia, bone marrow failure, and a predisposition to thrombosis. Accurate diagnosis of PNH is not straightforward and necessitates both flow cytometric evaluation of glycosyl phosphatidylinositol (GPI)-anchored protein expression on peripheral blood cells and bone marrow analysis for complete disease characterization. Effective management hinges on determining the relative contributions of hemolysis and marrow failure to the complex anemia observed in PNH. Complement inhibition via eculizumab presents a promising therapeutic avenue for hemolytic anemia. Stem cell transplantation offers potential curative benefits, but its application should be carefully considered on an individual basis due to the variable nature of PNH. PNH clone size and ethnic/geographic factors are implicated in thrombophilic tendencies, although a definitive consensus on prophylactic anticoagulation remains elusive. Thrombosis in PNH characteristically involves unusual sites such as hepatic, mesenteric, cerebral, and dermal veins. Indefinite anticoagulation is recommended following thromboembolic events, and thrombolytic therapy should be considered for acute hepatic vein thrombosis (Budd-Chiari syndrome). Pregnancy in PNH patients is high-risk, requiring meticulous management including prophylactic anticoagulation. The International PNH Registry was established to provide a broad perspective on the disease’s natural history, management strategies, and outcomes.
Defining and Classifying PNH for Accurate Diagnosis
PNH Definition
PNH arises from the non-malignant clonal expansion of hematopoietic stem cells harboring a somatic mutation in the PIGA gene. The progeny of these mutated stem cells exhibit a deficiency in glycosyl phosphatidylinositol-anchored proteins (GPI-APs). The absence of GPI-anchored complement regulatory proteins CD55 and CD59 is the primary cause of intravascular hemolysis, the most prominent clinical manifestation of PNH. PNH frequently co-occurs with bone marrow failure disorders, notably aplastic anemia. Thrombophilia is a significant source of morbidity and mortality in PNH.
PNH Classification
A classification system incorporating the diverse clinical presentations, manifestations, and disease progression in PNH patients has been developed (Table 1). Ongoing research may refine these categories, but currently, this three-tiered classification serves as a practical framework and common terminology within the field.
Table 1. Classification of PNH
| Category | Description
