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

• Caused by the absence of glycosyl-phosphatidylinositol (GPI), which anchors protective surface proteins.
• Lack of complement regulatory proteins (e.g., CD55, CD59) makes cells highly susceptible to complement-mediated lysis.
• PNH is classified as a rare bone marrow failure disorder.

Aetiology

• Abnormal red blood cells (RBCs) lack regulatory proteins that protect against complement activation.
• Mutations affect haematopoietic stem cells; white blood cells and platelets are also affected.
• Can be associated with myelodysplastic syndromes or acute leukaemia.
• An acquired genetic mutation (not inherited).
• Symptoms may worsen during illness or surgery.
• Diagnosis is confirmed by reduced or absent CD59/CD55 expression on RBCs.

Types of PNH

• Classical PNH: Presents with haemolytic anaemia and thrombosis.
• PNH with Other Bone Marrow Disorders: Coexists with aplastic anaemia or myelodysplastic syndrome.
• Subclinical PNH: Small PNH clones present but no active haemolysis or thrombosis.

Clinical Features

• Haemolytic anaemia, often exacerbated by infections or surgical stress.
• Venous thromboses (e.g., Budd-Chiari syndrome, cerebral venous sinus thrombosis, splenic or abdominal vein thrombosis).
• Dark or “cola-coloured” urine, especially noticeable in the morning (nocturnal haemoglobinuria).
• Bone marrow aplasia or hypoplasia in some patients.

Investigations

• Blood Counts: Low haemoglobin (anaemia), raised reticulocytes; WBC and platelets may also be reduced if there is bone marrow failure.
• Markers of Intravascular Haemolysis: Elevated LDH, low haptoglobin, haemoglobinuria, haemosiderinuria.
• Flow Cytometry: Demonstrates absence or reduced expression of CD59/CD55 on RBCs (primary diagnostic test).
• Other Tests (historical/less common): Ham test, sucrose lysis test, complement sensitivity test.

Management

• Eculizumab: Humanized monoclonal antibody against C5 that reduces haemolysis significantly.
• Supportive Care: Folate and iron supplementation.
• Corticosteroids: Prednisolone may decrease haemolysis but long-term toxicity is a concern.
• Stem Cell Transplant: Potentially curative in certain cases.
• Anticoagulation: Warfarin for thrombosis prophylaxis or treatment.

References

• Paroxysmal Nocturnal Haemoglobinuria – Blood Journal