Haemolysis is the premature destruction of red blood cells (RBCs), which normally circulate for approximately 120 days before being naturally cleared. When this destruction accelerates, the body develops haemolytic anaemia because the rate of RBC loss outpaces the bone marrow’s ability to produce new ones. This rapid breakdown releases haemoglobin into the bloodstream. The resulting build-up of waste products, particularly bilirubin, and the lack of oxygen transport make haemolysis a significant health concern.
How Red Blood Cells Break Down
RBC destruction occurs through two primary mechanisms: intravascular and extravascular haemolysis. Intravascular haemolysis involves the direct rupture (lysis) of RBCs while circulating within blood vessels, releasing free haemoglobin directly into the plasma.
Extravascular haemolysis is the more common process, taking place outside the blood vessels, primarily in the spleen and liver. Here, large immune cells called macrophages recognize and engulf RBCs that are structurally abnormal or coated with antibodies. The spleen acts as the main filter for clearing these damaged or aged cells.
When haemoglobin is released, its components are processed for recycling and disposal. The globin protein is broken down into amino acids that the body can reuse. The heme portion releases iron, which is conserved and reused by the body.
The remaining non-iron part of the heme molecule is converted first into biliverdin, and then into bilirubin. This bilirubin is initially unconjugated and insoluble. It must be transported to the liver to be chemically modified (conjugated) and made water-soluble. If the rate of red cell destruction is too rapid, the liver is overwhelmed, causing unconjugated bilirubin to accumulate in the bloodstream.
Triggers for Haemolysis
Haemolysis can be triggered by a wide variety of factors, which are grouped into categories based on their origin.
Inherited Defects
Genetic conditions cause defects within the red blood cell itself. In Sickle Cell Disease, a mutation causes haemoglobin to polymerize into stiff rods when deoxygenated, deforming the cell and leading to premature destruction. Other inherited defects include enzyme deficiencies, such as Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, which makes RBCs susceptible to oxidative stress. Conditions like Hereditary Spherocytosis involve a weakened cell membrane, causing cells to be easily trapped and destroyed in the spleen.
Immune-Mediated Triggers
These involve the body’s defense system mistakenly targeting healthy RBCs. Autoimmune Haemolytic Anaemia (AIHA) occurs when antibodies attach to the RBC surface, marking them for destruction by macrophages in the spleen and liver. A severe transfusion reaction is an acute example where antibodies react with incompatible donor cells, causing massive and rapid destruction.
Mechanical Trauma
Physical damage occurs when RBCs are subjected to high shear stress, such as passing through a defective prosthetic heart valve or synthetic graft. This sheer force fragments the cell membrane, resulting in intravascular haemolysis and the appearance of fragmented cells (schistocytes) on a blood smear.
Infectious and Toxic Agents
Pathogens, such as the parasite responsible for malaria, invade and multiply inside RBCs, physically rupturing them to complete their life cycle. Exposure to certain drugs, environmental toxins, or snake venom can also directly damage the red cell membrane, leading to acute haemolysis.
Physical Manifestations
The physical signs of haemolysis are primarily a consequence of the resulting anaemia and the liver’s struggle to process the breakdown products. Symptoms related to the body’s reduced oxygen-carrying capacity include persistent fatigue, weakness, and paleness of the skin and mucous membranes.
The excess bilirubin accumulates in the blood, leading to jaundice, visible as a yellowing of the skin and the whites of the eyes. Rapid RBC destruction can also cause the spleen to enlarge (splenomegaly) as it works overtime to filter and clear the damaged cells.
In cases of significant intravascular haemolysis, the massive release of free haemoglobin can exceed the binding capacity of plasma proteins. This unbound haemoglobin is filtered by the kidneys and excreted in the urine, causing a dark, reddish-brown appearance called haemoglobinuria. Other symptoms may include abdominal pain or the development of gallstones due to the chronic presence of excess bilirubin in the bile.
Diagnosis and Treatment Protocols
Diagnosis relies on identifying specific laboratory markers that confirm accelerated red blood cell destruction. Lactate Dehydrogenase (LDH), an enzyme found inside red blood cells, becomes elevated in the blood when the cells rupture. Another indicator is a reduced level of haptoglobin, a protein that binds to free haemoglobin in the plasma.
The presence of increased unconjugated bilirubin is a direct consequence of the haemoglobin breakdown process. The bone marrow attempts to compensate for the loss of cells by rapidly producing new ones, reflected by an elevated reticulocyte count. A blood smear is also performed to visually inspect for abnormally shaped or fragmented red blood cells, which offers clues about the cause.
Management strategies are highly dependent on the underlying cause of the haemolysis. Supportive care often involves blood transfusions to quickly raise the red blood cell count in severe anaemia. Folic acid supplementation is also provided, as the body needs this vitamin to fuel the increased production of new red blood cells.
For immune-mediated haemolysis, the first line of treatment involves immunosuppressive medications, such as corticosteroids, to decrease the immune system’s attack. If the cause is infectious, treatment focuses on eliminating the pathogen. In cases where the spleen is the main site of destruction, its surgical removal may be considered to prevent further accelerated red blood cell clearance.