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A rare acquired, life-threatening disease of the blood. The disease is characterized by the destruction of red blood cells (haemolytic anaemia), blood clots (thrombosis), and impaired bone marrow function

About

• Absence of glycosyl-phosphatidylinositol (GPI) which anchors several surface proteins and deficiency of complement regulatory proteins
• Cells become very sensitive to complement-mediated haemolysis. It is a rare bone marrow failure disorder

Aetiology

• Abnormal red blood cells lack the regulatory proteins that protect against complement-mediated damage
• However it now seems that both white cells and platelets share this disorder
• PNH is now considered to be due to a haematopoietic stem cell mutation defect
• The RBC/WBC/platelets share the disorder so PNH is now considered to be due to a haematopoietic stem cell mutation defect and even myelodysplasia and acute leukaemia can be seen
• There is an acquired genetic mutation and no evidence that is inherited
• Symptoms and haemolysis worsen with illness and surgery
• Absence or reduced expression of both CD59 and CD55 on PNH red cells is diagnostic of PNH

Three main types

• (1) classical PNH, which includes haemolytic and thrombotic patients
• (2) PNH in the context of other primary bone marrow disorders, such as aplastic anaemia or myelodysplastic syndrome; and
• (3) subclinical PNH, in which patients have small PNH clones but no clinical or laboratory evidence of haemolysis or thrombosis

Clinical

• Anaemia due to haemolysis worsens with illness and surgery
• Venous thrombosis: Budd Chiari syndrome, Cerebral Venous sinus thrombosis, Abdominal vein thrombosis, Splenic vein thrombosis which can cause an acute abdomen
• Dark urine after sleep as concentrated
• Bone marrow aplasia

Investigations

• Anaemia low Hb, Raised reticulocyte count, Bone marrow failure leads to low WCC and platelets
• Intravascular Haemolysis: High LDH x 10 fold, Low Haptoglobins, Haemoglobinuria, haemosiderinuria - cola coloured urine concentrated after sleep.
• Absence or decreased expression of glycophosphatidylinositol-linked proteins such as CD59 and CD55 on PNH red cells is diagnostic.
• Ham test shows Haemolysis when normal serum was acidified
• The sugar water or sucrose lysis test
• The complement lysis sensitivity test of Rosse and Dacie

Management

• Terminal complement inhibition with eculizumab and allogeneic bone marrow transplantation (BMT) are the only widely effective therapies for patients with classical PNH
• Treatment is supportive. Some improve spontaneously. Give Folate and Iron
• Eculizumab, is a humanized monoclonal antibody against terminal protein C5. It has recently been shown to be highly effective in reducing intravascular haemolysis.
• Prednisolone may be given. Corticosteroids can improve haemoglobin levels and reduce haemolysis is some PNH patients, but the long-term toxicity and limited efficacy limits enthusiasm for these agents.
• Stem cell transplantation is a curative therapeutic option
• Warfarin for thrombosis

References

• Paroxysmal nocturnal haemoglobinuria