Paroxysmal nocturnal haemoglobinuria (PNH)

Keywords: Paroxysmal nocturnal haemoglobinuria and hypoplastic myelodysplastic syndrome, PNH and hypoplastic MDS

PNH is a rare clonal haemopoietic disorder characterised by bone marrow failure, chronic haemolytic anaemia with acute episodes and thrombosis. PNH can arise either spontaneously or can occur in the setting of another marrow disorder such as aplastic anaemia and myelodysplastic syndromes.

PNH is caused by a mutation in the PIG-A gene in haematopoietic stem cell that leads to disruption of Glyco phosphatidyl inositol (GPI) synthesis and a deficiency of GPI linked proteins. This results in the absence of GPI-linked complement inhibitors CD55 and CD59, resulting in increased susceptibility to complement-mediated haemolysis.

Iron replacement often leads to an increase in haemolysis.

Presentation Appropriate Tests

 

Full blood count, Blood film, White cell count differential, Platelet count; Direct antiglobulin test; Reticulocyte count. Biochemical haemolytic indices.

Diagnosis may be made with Flow cytometry for PNH to detect absent or diminished expression eg Glyco phosphatidyl inositol (GPI) linked cell surface proteins on red cells or white cell sub-populations. 

Haemosiderin urine. Bone marrow aspiration and trephine biopsy with flow cytometry, iron stain and cytogentic studies.

See also Aplastic anaemia, Myelodysplastic syndromes, Haemolysis, Haemoglobinuria

Anaemia

 

Thrombosis

There is long term risk of major thrombotic episodes.

Abdominal pain

 

Progression to

  • Myelodysplastic syndromes
  • Acute leukaemia

See Myelodysplastic syndromes