Haemolysis can be caused by a wide variety of immune and non-immune conditions.

Thrombotic microangiopathies such as thrombotic thrombocytopaenic purpura (TTP), haemolytic-uraemic syndrome (HUS) and disseminated intravascular coagulation (DIC) are important causes of haemolysis and should not be missed. HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) may occur in pregnant patients. Mechanical haemolysis may be caused by severe valvular leaks, mechanical valves and other cardiac prostheses, by dialysis or ECMO circuits, or by repetitive trauma (e.g. by prolonged marching).

Autoimmune haemolytic anaemias may be either warm or cold. Their causes are wide ranging and include infections, autoimmune disorders, lymphoproliferative disorders and drugs. Alloimmune haemolysis may occur following mismatched blood transfusion, in newborns, or post stem cell transplantation. Certain drugs may also cause immune haemolysis.

Severe infections, malaria, meningococcal and Clostridium infections can cause haemolysis. Certain heavy metals such as copper and lead are also implicated. The syndrome of hypersplenism is a common cause in patients with liver disease, CCF or certain other conditions.

Inherited red blood cell disorders such as hereditary spherocytosis, sickle cell anaemia and thalassaemias are more rare. Glucose-6-phosphate dehydrogenase deficiency may cause oxidative haemolysis and is more common in males of African or Mediterranean descent.

Elevated unconjugated bilirubin is an indicator of haemolysis though can be caused by other disorders including resorption of a large haematoma, certain medications, inherited disorders, acute hepatitis or cirrhosis. As such it is important to also look at the remainder of the liver function panel when interpreting the bilirubin.

A reduced haptoglobin may also occur in the context of liver disease due to reduced production. As haptoglobin is an acute phase reactant, it may be increased in infection, inflammation, malignancy or trauma.

It is a non-specific marker of cell damage affecting any tissue, and is elevated in haemolysis. Other causes of elevated lactate dehydrogenase include infarction of any kind, malignancy, cirrhosis, trauma, shock and hypoxia.

Similarly, this free haemoglobin will be excreted in the urine; this will result in a dipstick that is positive for blood but with no red blood cells on microscopy.

The direct antiglobulin test (DAT), also known as the direct Coomb's, tests for IgG and complement 3 (C3) on the surface of red blood cells. The test is performed by adding antibodies against human IgG or C3 and monitoring for agglutination.

A positive direct antiglobulin test indicates an immune (autoimmune, alloimmune or drug-induced) cause of haemolysis, and may be positive before haemolysis occurs.

For a list of immune and non-immune causes of haemolysis, see the table at the top of the page.

Abnormal red blood cell morphology may provide clues regarding the presence or cause of haemolysis.

Microspherocytes are counted as schistocytes - they are small round cells with loss of central pallor.

Prekeratocytes, also known as blister cells, are similar to bite cells with a small sliver of membrane remaining over the bite.

Nucleated red blood cells are immature red blood cells that contain nuclei. They may present in the context of severe anaemia, severe sepsis, hypoxia or bone marrow disease.

Heinz bodies are basophilic denatured haemoglobin molecules that are present in the context of oxidative haemolysis. These may only be seen on supravital staining.