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Haemolysis – Causes, Symptoms and Treatment

Haemolysis is the breakdown of red blood cells, releasing haemoglobin into the bloodstream. It can range from a normal process to a life-threatening condition.

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Things worth knowing about "Haemolysis"

Haemolysis is the breakdown of red blood cells, releasing haemoglobin into the bloodstream. It can range from a normal process to a life-threatening condition.

What is Haemolysis?

Haemolysis refers to the destruction or breakdown of red blood cells (erythrocytes), which causes the release of their oxygen-carrying protein, haemoglobin, into the surrounding plasma or bloodstream. A small degree of haemolysis is a normal physiological process, as ageing red blood cells are naturally removed after approximately 120 days. However, when haemolysis becomes accelerated or pathological, it can overwhelm the body's compensatory mechanisms and lead to haemolytic anaemia -- a reduction in healthy red blood cells that impairs oxygen delivery to tissues.

Causes

Haemolysis can be classified based on whether the cause originates within the red blood cell itself (intrinsic/corpuscular haemolysis) or from external factors (extrinsic/extracorpuscular haemolysis).

Intrinsic (Corpuscular) Causes

Inherited conditions: Sickle cell disease, thalassaemia, hereditary spherocytosis
Enzyme deficiencies: Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)
Haemoglobinopathies: Structural abnormalities of haemoglobin

Extrinsic (Extracorpuscular) Causes

Immune-mediated: Autoimmune haemolytic anaemia, blood transfusion reactions (ABO incompatibility)
Infections: Malaria, certain bacterial infections (e.g., Clostridium perfringens)
Mechanical causes: Prosthetic heart valves, microangiopathic haemolytic anaemia (e.g., thrombotic thrombocytopenic purpura, TTP)
Toxic causes: Snake venoms, certain drugs (e.g., dapsone), industrial chemicals
Physical causes: Severe burns, extreme osmotic stress

Symptoms

The clinical presentation of haemolysis depends on the rate and severity of red blood cell destruction. Common signs and symptoms include:

Anaemia symptoms: Pallor, fatigue, weakness, shortness of breath, rapid heart rate
Jaundice (icterus): Yellowing of the skin and whites of the eyes due to elevated bilirubin levels (a breakdown product of haemoglobin)
Dark urine: Caused by free haemoglobin in the urine (haemoglobinuria) or urobilinogen
Enlarged spleen (splenomegaly): The spleen enlarges as it filters increased numbers of damaged red blood cells
Gallstones: Excess bilirubin from haemolysis can precipitate as pigment gallstones

Acute severe haemolysis can result in a haemolytic crisis, which is a medical emergency requiring immediate intervention.

Diagnosis

Diagnosis is established through clinical assessment and laboratory testing:

Full blood count (FBC): Low haemoglobin (anaemia) and elevated reticulocyte count (young red blood cells indicating increased bone marrow production)
Serum markers: Elevated indirect bilirubin, reduced or undetectable haptoglobin (a protein that binds free haemoglobin and is depleted during haemolysis)
Lactate dehydrogenase (LDH): Elevated due to release from lysed cells
Direct antiglobulin test (DAT / Coombs test): Detects antibodies on red blood cells in immune-mediated haemolysis
Blood film (peripheral smear): Microscopic evaluation for abnormal red cell morphology (e.g., sickle cells, spherocytes, schistocytes/fragmented cells)
Urine dipstick: Detects haemoglobinuria

Treatment

Treatment of haemolysis is directed at the underlying cause:

Immune haemolytic anaemia: Corticosteroids, immunosuppressants, intravenous immunoglobulins, and in selected cases splenectomy (surgical removal of the spleen)
Infection-related haemolysis (e.g., malaria): Targeted antimicrobial or antiparasitic therapy
Toxic haemolysis: Removal or discontinuation of the causative agent, supportive care
Hereditary haemolytic conditions: Symptomatic management; in severe cases blood transfusions or bone marrow transplantation
Acute severe haemolysis: Emergency management including fluid resuscitation, transfusion support, and intensive care monitoring

References

Longo, D.L. et al. - Harrison's Principles of Internal Medicine, 21st Edition. McGraw-Hill, 2022.
Barcellini, W. & Fattizzo, B. - Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Monitoring of Hemolytic Anemia. Disease Markers, 2015. PubMed PMID: 26609218.
World Health Organization (WHO) - Sickle-cell disease and other haemoglobin disorders. Available at: https://www.who.int (accessed 2024).

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