Which of the following is the best test for diagnosis of paroxysmal nocturnal hemoglobinuria?
**Core Concept**
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by the complement-mediated destruction of red blood cells, leading to hemolytic anemia. The diagnosis of PNH requires identification of a mutation in the PIGA gene, which is responsible for the synthesis of glycosylphosphatidylinositol (GPI).
**Why the Correct Answer is Right**
The best test for diagnosing PNH is the flow cytometric analysis of blood cells for the absence of GPI-anchored proteins, such as CD55 and CD59. This is because PNH stem cells have a mutation in the PIGA gene, which prevents the expression of GPI-anchored proteins on the surface of blood cells. Flow cytometry can detect the absence of these proteins on the surface of red blood cells, white blood cells, and platelets.
**Why Each Wrong Option is Incorrect**
**Option A:** Hemoglobin electrophoresis is a test used to diagnose various hemoglobinopathies, such as sickle cell disease or thalassemia, but it is not useful for diagnosing PNH.
**Option B:** Serum lactate dehydrogenase (LDH) levels can be elevated in PNH due to hemolysis, but this is a non-specific finding and not a definitive test for PNH.
**Option C:** Bone marrow biopsy may show erythroid hyperplasia and dysplasia in PNH, but it is not a specific test for diagnosing PNH.
**Clinical Pearl / High-Yield Fact**
PNH is often associated with thrombosis, particularly in the venous system, and patients with PNH should be screened regularly for thrombotic events.
**Correct Answer:** . Flow cytometric analysis of blood cells for the absence of GPI-anchored proteins.