What is Paroxysmal nocturnal haemoglobinuria?

life-threatening disease of the blood characterized by destruction of red blood cells by the complement system

What is the Pathophysiology of Paroxysmal nocturnal haemoglobinuria?

• complement-regulating surface proteins, are not properly bound to the cell membrane due a lack of GPI
  • glycoprotein glycosyl-phosphatidylinositol (GPI) can be thought of as an anchor which attaches surface proteins to the cell membrane
• thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation

What is seen in blood tests in Paroxysmal nocturnal haemoglobinuria?

• haemolytic anaemia
• red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present

What are the clinical features of Paroxysmal nocturnal haemoglobinuria?

• haemolytic anaemia
• pancytopaenia may be present
• aplastic anaemia may develop in some patients
• haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
• thrombosis e.g. Budd-Chiari syndrome

How is Paroxysmal nocturnal haemoglobinuria diagnosed?

flow cytometry of blood to detect low levels of CD59 and CD55

What is the management of Paroxysmal nocturnal haemoglobinuria?

• blood product replacement
• anticoagulation
• eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis
• stem cell transplantation