Makindo Medical Notes

Related Subjects: |Sideroblastic Anaemia |Splenectomy |Paroxysmal Nocturnal Haemoglobinuria |Pernicious anaemia |Normocytic anaemiaa |Pyruvate Kinase deficiency |Blood Products - Platelets |Von Willebrand Disease

Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare, acquired, and potentially life-threatening blood disorder. It is primarily characterized by the destruction of red blood cells (haemolytic anaemia), blood clot formation (thrombosis), and impaired bone marrow function.

About

• It is caused by the absence of glycosyl-phosphatidylinositol (GPI), which anchors several protective surface proteins.
• The deficiency of complement regulatory proteins makes cells highly sensitive to complement-mediated haemolysis.
• PNH is classified as a rare bone marrow failure disorder.

Aetiology

• Abnormal red blood cells lack regulatory proteins that protect against complement-mediated damage.
• White blood cells and platelets also share this abnormality.
• PNH arises from a haematopoietic stem cell mutation and can be associated with myelodysplasia and acute leukaemia.
• The condition is not inherited but caused by an acquired genetic mutation.
• Symptoms often worsen during illness or surgery.
• Diagnosis is confirmed by the absence or reduced expression of CD59 and CD55 on red blood cells.

Types of PNH

• Classical PNH: Patients exhibit haemolytic anaemia and thrombosis.
• PNH with other bone marrow disorders: Associated with aplastic anaemia or myelodysplastic syndrome.
• Subclinical PNH: Patients have small PNH clones but no evidence of haemolysis or thrombosis.

Clinical Features

• Anaemia due to haemolysis, often exacerbated by illness or surgery.
• Venous thrombosis e.g. Budd-Chiari syndrome, cerebral venous sinus thrombosis, abdominal/splenic vein thrombosis.
• Dark-coloured urine after sleep due to concentrated haemoglobinuria.
• Bone marrow aplasia.

Investigations

• Anaemia: Low haemoglobin levels, raised reticulocyte count.
• Bone marrow failure: Low white blood cell (WBC) and platelet counts.
• Intravascular haemolysis: Elevated LDH, low haptoglobin, haemoglobinuria, and haemosiderinuria (cola-colored urine after sleep).
• Diagnostic tests: Absence or reduced expression of CD59 and CD55 on red blood cells, Ham test, sucrose lysis test, and complement lysis sensitivity test.

Management

• Eculizumab: A humanized monoclonal antibody targeting complement protein C5, highly effective in reducing haemolysis.
• Supportive treatment: Folate and iron supplementation.
• Prednisolone: Can reduce haemolysis in some patients, but long-term toxicity limits its use.
• Stem cell transplantation: A curative option for some patients.
• Warfarin: Prescribed for the prevention or treatment of thrombosis.

References

• Paroxysmal Nocturnal Haemoglobinuria - Blood Journal