Anaemia - Haemolytic Anaemia - Paroxysmal Nocturnal Haemoglobinuria

Question 1

What is PNH?

Answer 1

Paroxysmal Nocturnal Haemoglobinuria - an acquired intravascular haemolysis.

Question 2

Aetiology of PNH (4).

Answer 2

1. Genetic mutation in Haematopoietic Stem Cells in Bone Marrow occurs.
2. Loss of proteins on surface of RBCs (that inhibit the Complement Cascade).
3. Activation of Complement Cascade.
4. Destruction of RBCs.

Question 3

Which protein is lost?

Answer 3

Glycoprotein Glycosyl-Phosphatidylinositol (GPI).

Question 4

What is the role of GPI?

Answer 4

Anchor that attaches complement-regulating surface proteins e.g. DAF (Decay Accelerating Factor) to the cell membrane isn’t present.

Question 5

Clinical Presentation of PNH (3).

Answer 5

1. Red Urine AM (containing Haemoglobin and Haemosiderin).
2. Anaemia + (Potentially Pancytopenia).
3. Predisposition to Thrombosis and Smooth Muscle Dystonia (e.g. Oesophageal Spasm and Erectile Dysfunction).

Question 6

What results in a predisposition to Thrombosis?

Answer 6

A lack of CD59 on platelet membranes predisposes one to platelet aggregation.

Question 7

Investigations of PNH (2).

Answer 7

1. Flow Cytometry = Low Levels of CD59 and CD55 - Gold Standard (previously Ham’s Test).
2. Ham’s Test - Acid-Induced Haemolysis (unlike normal RBCs).

Question 8

Management of PNH (3).

Answer 8

1. Eculizumab (monoclonal antibody targeting C5).
2. Bone Marrow Transplant (curative).
3. Anticoagulation.