Guideline Summary for Diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)

Risk Stratification

Patients with a PNH clone comprising >60 % GPI‑deficient granulocytes have a markedly increased risk of thrombosis. 1

All individuals with Budd‑Chiari syndrome should be screened for PNH because 9–19 % are found to have the disease. [1][2]
Screening is also reasonable in patients with portal vein thrombosis, although the prevalence is low (0–2 %). 1
Myelodysplastic syndrome (MDS) work‑up should incorporate PNH testing to identify co‑existing clonal hemolysis. [3][4]
Patients with aplastic anemia or other bone‑marrow‑failure syndromes require evaluation for PNH. 5

Elevated indirect bilirubin together with decreased haptoglobin is a typical laboratory pattern indicating intravascular hemolysis. 6
Peripheral blood smear frequently shows morphological evidence of hemolysis (e.g., schistocytes, reticulocytosis). 6
Increased free hemoglobin in plasma is another marker of ongoing hemolysis. 6

Initial laboratory assessment should include a complete blood count with differential, reticulocyte count, and peripheral smear examination. 6
A hemolysis panel (LDH, total and indirect bilirubin, haptoglobin, free hemoglobin) is recommended to confirm intravascular hemolysis. 6
Perform a direct antiglobulin test (DAT) to exclude autoimmune hemolytic anemia as an alternative cause. 6
Flow cytometry on peripheral blood must be used to detect deficiency of GPI‑anchored proteins (CD55, CD59) on granulocytes, monocytes, and red blood cells.
Quantify the PNH clone size in granulocytes, monocytes, and red blood cells to inform risk assessment and therapeutic decisions. 1

In patients with bone‑marrow failure or hypocellular marrow, the PNH clone may be masked; therefore, flow cytometry remains essential for detection. 5
When cytopenias suggest an underlying marrow disorder (e.g., MDS), a bone‑marrow examination should be performed to clarify the hematologic context. 5