22nd July 2024

Hereditary haemolysis

RBC membrane defects

Hereditary spherocytosis

An autosomal dominant condition most prevalent in people descended from Northern Europe. There is a deficiency of cell membrane proteins leading to a more spherical RBC compared to the normal biconcave shape, with a raised mean corpuscular haemoglobin concentration (MCHC) (typically >36 g/dL). The abnormal RBCs, called spherocytes (Figure 5) have a reduced lifespan as well as reduced mechanical stability and deformability, which can cause membrane loss and phagocytosis within the spleen. In turn, this leads to an even more spherical shape and reduced mobility through the circulation leading to haemolysis.

A diagnosis can be made clinically and patients often have a family history as well as bloods consistent with a chronic haemolytic anaemia. If there is uncertainty, the specific EMA (eosin-5′-maleimide) binding test can be used. Osmotic fragility testing is possible but has poor sensitivity and specificity. Acute exacerbations can occur secondary to infection, nutritional deficiencies or pregnancy, due to either increased haemolysis or inadequate RBC production.

Treatment aims to minimise complications and may include folic acid supplementation, RBC transfusions, erythropoietin, splenectomy and cholecystectomy (patients are at risk of pigment gallstones made up of bilirubin). Following splenectomy patients will have signs of reduced splenic function, for example Howell-Jolly bodies (nuclear remnants within RBCs) and are more at risk of infection from encapsulated bacteria.

Hereditary elliptocytosis

An autosomal dominant condition with a similar pathophysiology to hereditary spherocytosis, but is rarer and often asymptomatic or causes only mild disease.

Image Source: Wikimedia Commons (2010). Hereditary Spherocytosis smear 2010-03-17, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/6/69/Hereditary_Spherocytosis_smear_2010-03-17.JPG (Accessed: 16 January 2024)

Enzyme deficiencies

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

G6PD deficiency is an X-linked recessive condition, which therefore generally affects males, often of Mediterranean, African or middle and far Eastern descent. There is mainly intravascular haemolysis.

It can present in the newborn, commonly with neonatal jaundice, or with episodes of acute haemolysis secondary to triggers including ​​drugs (primaquine, sulfonamides, henna dye), fava beans and intercurrent illness, or with chronic haemolytic anaemia.

Investigations include those mentioned previously to assess for haemolysis. The blood film may show bite cells (semicircular indent on RBC) and blister cells (vacuole on the edge of the RBC membrane), and Heinz bodies. A G6PD enzyme assay should be performed. This needs to be done 8-12 weeks after an acute haemolytic crisis to avoid a falsely elevated result, as reticulocytes have high levels of the enzyme, but levels decrease as RBCs mature.

Treatments include RBC transfusion if symptomatic anaemia or severe haemolysis and avoidance of triggers.

Pyruvate kinase (PK) deficiency

This is an autosomal recessive condition which often presents with neonatal jaundice, followed by unexplained chronic anaemia later in life with splenomegaly ± gallstones. There is mainly extravascular haemolysis.

Investigations include an enzyme assay to assess PK activity as well as genetic testing.

Treatment is often supportive with folic acid and RBC transfusions if needed. Splenectomy can help reduce haemolysis if there is severe disease.

Haemoglobinopathies

These include thalassaemia and sickle cell anaemia.