## Diagnosis: Paroxysmal Nocturnal Hemoglobinuria (PNH) The clinical presentation of chronic hemolytic anemia with thrombosis risk, combined with **absence of CD55 and CD59** (complement regulatory proteins), is pathognomonic for PNH. ### Why Flow Cytometry with Anti-CD55 and Anti-CD59 is Most Specific **Key Point:** PNH results from a somatic mutation in the **PIGA gene**, which encodes phosphatidylinositol glycan anchor (PIG-A). This prevents synthesis of GPI-anchored proteins, including: - **CD55** (decay-accelerating factor, DAF) - **CD59** (membrane inhibitor of reactive lysis, MIRL) **High-Yield:** Flow cytometry detecting **absence of CD55 and CD59** is the **gold standard** and most specific test for PNH because: - It directly detects the molecular defect (GPI-anchor deficiency) - Has **100% specificity** for PNH - Quantifies the proportion of abnormal clones - Can detect small populations (>1% of cells) - Is **flow cytometric confirmation** of the diagnosis **Clinical Pearl:** PNH is characterized by the triad of hemolytic anemia, thrombosis, and cytopenias. The absence of GPI-anchored proteins on blood cells is the pathologic hallmark. ### Investigation Comparison for PNH Diagnosis | Investigation | Principle | Sensitivity | Specificity | Current Status | | --- | --- | --- | --- | --- | | **Flow cytometry (CD55/CD59)** | Detects GPI-anchor deficiency | >99% | 100% | **Gold standard** | | Sucrose lysis test | Osmotic lysis in hypotonic sucrose | 80–90% | 95% | Obsolete; replaced by flow | | Acidified serum lysis (Ham test) | Complement-mediated lysis in acidified serum | 70–80% | 90% | Historical; rarely used now | | DAT with anti-C3d | Detects C3 on RBC surface | Moderate | Low | Non-specific; may be positive in PNH | **Mnemonic:** **GPI = Gone (absent) in PNH** — loss of GPI-anchored proteins (CD55, CD59) is the defining feature.
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