24th May 2023

Non-immune-mediated haemolytic anaemia

The inherited causes of haemolysis covered previously are associated to some degree with non-immune mediated haemolysis.

Other causes include infection, trauma e.g. mechanical heart valves, drugs, and thrombotic microangiopathies. Examples are listed in the table below:

Paroxysmal Nocturnal Haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, haemolytic anaemia, characterised by intravascular haemolysis and is associated with bone marrow hypoplasia. It occurs due to an absence of glycosylphosphatidylinositol (GPI)-anchored proteins on the RBC membrane, which when present, inhibit formation of C3 convertases and prevent terminal polymerisation of the membrane attack complex, thereby protecting the cell from destruction. The absence of these GPI-anchored proteins, CD55 and CD59, leads to complement-mediated destruction of RBCs and WBCs. PNH is a thrombophilic condition and so can be complicated by venous (and less commonly arterial) thrombosis.

Its name comes from the association in some patients with episodic red discolouration of the urine due to the presence of haemoglobin and haemosiderin in the urine from haemolysed red blood cells. The discolouration is more pronounced in the mornings when the urine is more concentrated, hence the name paroxysmal nocturnal haemoglobinuria.

Clinical features – anaemia, fatigue, dyspnoea, haemoglobinuria, thrombosis e.g. symptoms of Budd-Chiari syndrome.

Laboratory bloods – low haemoglobin, may be low WCC or platelets, raised reticulocytes, low haptoglobin, raised lactate dehydrogenase, raised unconjugated bilirubin, consider D-dimer.

Other tests – Flow cytometry for CD55 and CD59 on RBC and WBC has now superseded the historical ‘Ham’s acid haemolysis test’. Fluorescein-labelled proaerolysin (FLAER) is an increasingly used test which is currently the most sensitive and accurate test for diagnosing PNH.

Direct Antiglobulin Test – negative, as the haemolysis is not caused by antibodies.

Management – Allogeneic bone marrow transplant is the only cure but is associated with significant morbidity. Eculizumab is a monoclonal antibody which can be used in certain cases which improves anaemia and quality of life. Other management includes RBC transfusion if required and treatment of thrombosis.