Which of the following laboratory findings is most specific for paroxysmal nocturnal hemoglobinuria (PNH)?

Question

Accepted Answer

B. Absence of CD55 and CD59 on blood cells detected by flow cytometry. ## Paroxysmal Nocturnal Hemoglobinuria: Flow Cytometry Diagnosis

**Key Point:** PNH is caused by a somatic mutation in the PIGA gene, leading to deficiency of glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins CD55 (DAF) and CD59 (MAC-inhibitory protein). Flow cytometry demonstrating absence of these proteins is the gold standard diagnostic test.

### Pathophysiology
1. **PIGA gene mutation:** Occurs in hematopoietic stem cells (somatic, acquired mutation)
2. **Loss of GPI anchor:** Cells cannot display GPI-anchored proteins
3. **Missing complement regulators:**
   - **CD55 (DAF):** Decay-accelerating factor — inhibits C3/C5 convertase
   - **CD59 (MAC-IP):** Membrane inhibitor of reactive lysis — blocks C5b-9 complex formation
4. **Result:** Uncontrolled complement activation → intravascular hemolysis, thrombosis, and cytopenias

### Diagnostic Approach

| Test | Finding in PNH | Specificity |
|------|---|---|
| **Flow cytometry (CD55/CD59)** | Absent on RBCs, WBCs, platelets | **Gold standard — most specific** |
| **Ham test (acidified serum)** | Hemolysis in acidified serum | Positive but less sensitive; rarely used now |
| **Sucrose lysis test** | Osmotic lysis in sucrose | Positive but less specific |
| **Hemoglobinuria** | Dark urine (especially morning) | Supportive but not diagnostic |
| **Reticulocytosis** | Elevated | Nonspecific |
| **LDH, bilirubin** | Elevated | Nonspecific |

**High-Yield:** Flow cytometry for CD55 and CD59 is the **modern diagnostic gold standard** for PNH. It is more sensitive and specific than the older Ham test or sucrose lysis test.

**Clinical Pearl:** PNH presents with a triad:
1. **Hemolysis** (intravascular, episodic)
2. **Thrombosis** (venous, especially hepatic vein — Budd-Chiari syndrome)
3. **Cytopenias** (due to bone marrow involvement)

**Mnemonic:** **PNH = GPI loss → CD55/CD59 absent → Complement uncontrolled → Hemolysis + Thrombosis + Cytopenias**

Answer

A. Elevated osmotic fragility on osmotic fragility test

Answer

C. Presence of Heinz bodies on supravital staining

Answer

D. Positive direct antiglobulin test (Coombs test)

Which of the following laboratory findings is most specific for paroxysmal nocturnal hemoglobinuria (PNH)?

Explanation

Paroxysmal Nocturnal Hemoglobinuria: Flow Cytometry Diagnosis

Pathophysiology

Diagnostic Approach

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Test	Finding in PNH	Specificity
Flow cytometry (CD55/CD59)	Absent on RBCs, WBCs, platelets	Gold standard — most specific
Ham test (acidified serum)	Hemolysis in acidified serum	Positive but less sensitive; rarely used now
Sucrose lysis test	Osmotic lysis in sucrose	Positive but less specific
Hemoglobinuria	Dark urine (especially morning)	Supportive but not diagnostic
Reticulocytosis	Elevated	Nonspecific
LDH, bilirubin	Elevated	Nonspecific