Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal Nocturnal Hemoglobinuria (PNH) is caused by the mutation of PIGA gene in hematopoietic stem cells; PIGA gene is required for the synthesis of glycosylphosphatidylinositol (GPI) protein on cell surface; Mutation of PIGA gene leads to deficiency of GPI and subsequently deficiency of its anchored proteins CD55 and CD59 (CD55 and CD59 is secured to the cell membrane by GPI; CD55/DAF and CD59/MIRL are the inhibitors of complement).

Presents with coombs negative hemolytic anemia, pancytopenia and venous thrombosis.

Diagnosis:-

1. CBC shows pancytopenia.

2. Sucrose lysis test is used for screening.

3. Flow cytometry detects absence of anchored proteins CD55 and CD59 and is the confirmatory test. 

4. Laboratory studies show low hemoglobin, increased reticulocytes, increased indirect bilirubin, increased LDH and decreased haptoglobin.

Management:-

1. Supportive measures include iron, folate supplementation, blood transfusions and anticoagulation.

2. Steroids. 

3. Eculizumab is the monoclonal antibodies to C5 that inhibits activation of the terminal complement pathway) and reduces hemolysis; It is associated with increased susceptibility to neisseria infections. Hence, patients should receive meningococcal vaccination before receiving eculizumab.

4. Allogeneic bone marrow transplant.