Haemolytic anaemia is where there is destruction of red blood cells (haemolysis) leading to anaemia. There are a number of inherited conditions that cause the red blood cells to be more fragile and break down faster than normal leading to chronic haemolytic anaemia. There are also a number of acquired conditions that lead to increased breakdown of red blood cells and haemolytic anaemia.
Inherited Haemolytic Anaemias
- Hereditary Spherocytosis
- Hereditary Elliptocytosis
- Sickle Cell Anaemia
- G6PD Deficiency
Acquired Haemolytic Anaemias
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia (transfusions reactions and haemolytic disease of newborn)
- Paroxysmal nocturnal haemoglobinuria
- Microangiopathic haemolytic anaemia
- Prosthetic valve related haemolysis
The features are a result of the destruction of red blood cells:
- Anaemia due to the reduction in circulating red blood cells
- Splenomegaly as the spleen becomes filled with destroyed red blood cells
- Jaundice as bilirubin is released during the destruction of red blood cells
- Full blood count shows a normocytic anaemia
- Blood film shows schistocytes (fragments of red blood cells)
- Direct Coombs test is positive in autoimmune haemolytic anaemia
Hereditary spherocytosis is the most common inherited haemolytic anaemia in northern Europeans. It is an autosomal dominant condition. It causes sphere shaped red blood cells that are fragile and easily break down when passing through the spleen.
It presents with jaundice, gallstones, splenomegaly and notably aplastic crisis in the presence of the parvovirus. It is diagnosed by family history and clinical features with spherocytes on the blood film. The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count. Reticulocytes will be raised due to rapid turnover of red blood cells.
Treatment is with folate supplementation and splenectomy. Removal of the gallbladder (cholecystectomy) may be required if gallstones are a problem.
Hereditary elliptocytosis is very similar to hereditary spherocytosis except that the red blood cells are ellipse shaped. It is also autosomal dominant. Presentation and management are the same.
G6PD deficiency is a condition where there is a defect in the red blood cell enzyme G6PD. It is more common in Mediterranean and African patients and is X linked recessive. It causes crises that are triggered by infections, medications or fava beans (broad beans).
It presents with jaundice (usually in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on blood film. Diagnosis can be made by doing a G6PD enzyme assay.
Medications that trigger haemolysis include primaquine (an antimalarial), ciprofloxacin, sulfonylureas, sulfasalazine and other sulphonamide drugs.
TOM TIP: The key piece of knowledge for G6PD deficiency relates to triggers. In your exam look out for a patient that turns jaundice and becomes anaemic after eating broad beans, developing an infection or being treated with antimalarials. The underlying diagnosis might be G6PD deficiency.
Autoimmune Haemolytic Anaemia (AIHA)
Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells. These antibodies lead to destruction of the red blood cells. There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells.
Warm Type Autoimmune Haemolytic Anaemia
Warm type autoimmune haemolytic anaemia is the more common type. Haemolysis occurs at normal or above normal temperatures. It is usually idiopathic, meaning that it arises without a clear cause.
Cold Type Autoimmune Haemolytic Anaemia
This is also called cold agglutinin disease. At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together. This is called agglutination. This agglutination results in the destruction of the red blood cells as the immune system is activated against them and they get filtered and destroyed in the spleen. Cold type AIHA is often secondary to other conditions such as lymphoma, leukaemia, systemic lupus erythematosus and infections such as mycoplasma, EBV, CMV and HIV.
Management of autoimmune haemolytic anaemia:
- Blood transfusions
- Prednisolone (steroids)
- Rituximab (a monoclonal antibody against B cells)
Alloimmune Haemolytic Anaemia
Alloimmune haemolytic anaemia occurs where an there is either foreign red blood cells circulating in the patients blood causing an immune reaction that destroys those red blood cells or there is a foreign antibody circulating in their blood that acts against their own red blood cells and causes haemolysis. The two scenarios where this occurs are transfusion reactions and haemolytic disease of the newborn.
In hemolytic transfusion reactions red blood cells are transfused into the patient. The immune system produces antibodies against antigens on those foreign red blood cells. This creates an immune response that leads to the destruction of those red blood cells.
In haemolytic disease of the newborn there are antibodies that cross the placenta from the mother to the fetus. These maternal antibodies target antigens on the red blood cells of the fetus. This causes destruction of the red blood cells in the fetus and neonate.
Paroxysmal Nocturnal Haemoglobinuria
Paroxysmal nocturnal haemoglobinuria is a rare condition that occurs when a specific genetic mutation in the haematopoietic stem cells in the bone barrow occurs during the patients lifetime. The specific mutation results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade. The loss of protection against the complement system results in activation of the complement cascade on the surface of red blood cells and destruction of the red blood cells.
The characteristic presentation is red urine in the morning containing haemoglobin and haemosiderin. The patient becomes anaemic due to the haemolysis. They are also predisposed to thrombosis (e.g. DVT, PE and hepatic vein thrombosis) and smooth muscle dystonia (e.g. oesophageal spasm and erectile dysfunction).
Management is with eculizumab or bone marrow transplantation. Eculizumab is a monoclonal antibody that targets complement component 5 (C5) causing suppression of the complement system. Bone marrow transplantation can be curative.
Microangiopathic Haemolytic Anaemia (MAHA)
Microangiopathic haemolytic anaemia (MAHA) is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. Imagine a mesh inside the small blood vessels shredding the red blood cells. This is usually secondary to an underlying condition:
- Haemolytic Uraemic Syndrome (HUS)
- Disseminated Intravascular Coagulation (DIC)
- Thrombotic Thrombocytopenia Purpura (TTP)
- Systemic Lupus Erythematosus (SLE)
Prosthetic Valve Haemolysis
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement. It is caused by turbulence around the valve and collision of red blood cells with the implanted valve. Basically the valve churns up the cells and they break down.
- Oral iron
- Blood transfusion if severe
- Revision surgery may be required in severe cases
Last updated April 2019