The red blood cells (RBCs or erythrocytes) are important carriers of gas in the blood ensuring that oxygen reaches all tissues. These cells are constantly being produced and destroyed in the body. The balance ensures that there is a sufficient quantity of RBCs in the blood. The normal lifespan of a red blood cell is about 120 days and usually wear and tear eventually leads to its destruction. This occurs at a steady rate in line with the production to ensure that there is neither an excess nor a deficiency of red blood cells.
What is hemolytic anemia?
Hemolytic anemia is a low level of circulating red blood cells due to its premature and often excessive destruction. The rate at which the red blood cells are destroyed are greater than the rate of its production in the bone marrow. This leads to a net loss and ultimately deficiency of red blood cells. The bone marrow can increase production by up to 800% to compensate for any sudden need of red blood cells. However in hemolytic anemia, the balance shifts in the favor of the destruction of red blood cells with or without a concomitant decrease in cell production.
Red blood cell destruction occurs in the liver, spleen and even the bone marrow. Mononuclear phagocytes identify these cells as being worn out or deformed and then destroy it. In hemolytic anemia, the excessive destruction of the red blood cells most commonly occurs within the phagocytes and it is therefore termed as extravascular hemolysis. However, in minority of cases the red blood cells are destroyed due to mechanical damage, external toxins, parasites that enter the cell or immune proteins (complement) that attach to the blood cell and triggers its destruction. This is known as intravascular hemolysis.
Effects of Excessive Red Blood Cell Destruction
Once a red blood cell is destroyed, its hemoglobin is still present in the body. This is broken down at a constant rate by certain cells particularly in the liver yielding hemosiderin and then bilirubin. However, with hemolytic anemia the destruction is so great that hemoglobin builds up in the blood and urine, as well as the hemosiderin and bilirubin. These byproducts are toxic to various cells in the body thus resulting a number of effects on different tissues in the body.
Patients with hemolytic anemia will therefore present with jaundice and spleen enlargement (splenomegaly) if it is due to extravascular causes. This is a result of the body’s normal destruction process and clearing sites being overburdened with the massive red blood cell destruction. In intravascular causes, there is a rise in free hemoglobin and hemosiderin in the blood and urine as well as jaundice. Anemia is obviously present in all cases.
Causes of Hemolytic Anemia
The causes of hemolytic anemia can be classified as inherited or acquired.
The inherited causes arise due to genetic defects that may lead to deformities in the cell membrane, internal components like hemoglobin or the lack of protective enzymes in the red blood cells. This is seen in conditions such as :
- Hereditary spherocytosis – abnormal sphere-shaped red blood cells.
- Hereditary elliptocytosis – abnormal elliptical shape of the red blood cells.
- Thalassemia – alpha or beta where there is an abnormality in the hemoglobin structure.
- Sickle cell disease – abnormal crescent shaped red blood cells.
- Red blood cell enzyme defects or deficiencies(enzymopathies) – glucose-6-phosphate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency, pyrimidine nucleotidase deficiency.
Acquired causes are a result of some disease process that is not related to birth defects or genetic alterations. This may include :
- Red blood cell infection like malaria.
- Mechanical damage to the red blood cells due to causes such as heart valve abnormalities or its passage through narrowed blood vessels. It may also be seen with strenuous physical exercise (march hemoglobinuria).
- Toxins associated with Clostridium perfringins septicemia.
- Auto-antibodies that bind to the red blood cell membranes – cold and warm autoimmune hemolytic anemias.
Autoimmune Hemolytic Anemias
This type of hemolytic anemia occurs with red blood cell auto-antibodies which “mark” the red blood cell for destruction. It often occurs for no known reason and is termed idiopathic autoimmune hemolytic anemia. It may, however, be seen with certain autoimmune diseases (secondary). There are two subtypes associated with antibody activity at certain temperatures – warm antibody type (warm autoimmune hemolysis) and cold antibody type (cold agglutinin disease).
Warm Antibody Type
This is more common and associated with temperatures of about 37 degrees Celsius (normal body temperature) which is optimal for the antibodies to bind. Warm antibody type autoimmune hemolytic anemia may be seen secondary to several conditions including :
- Autoimmune disease like SLE and rheumatoid arthritis.
- Other immune-related disorders like HIV infection.
- Neoplasm (cancer) of the lymphoid tissue like lymphoma or leukemia or solid malignant growths.
- Drugs including penicillin, quinidine and methyldopa.
Cold Antibody Type
Antibody binding is best at low temperatures around 4 degrees Celsius but can still occur at temperatures up to 37 degrees Celsius. It is seen with diseases such as B-cell lymphoma, Mycoplasma pneumoniae infection or with infectious mononucleosis.
Rare Types of Hemolytic Anemia
An uncommon type of autoimmune anemia is where the antibodies target red blood cells that do not “belong” in the body (non-self cells). This is known as alloimmune hemolytic anemia and may occur with massive blood transfusion or in the fetus/newborn baby where the mother’s immune system attacks the “father’s” antibodies (erythroblastosis fetalis). This is discussed further under neonatal jaundice.
Paroxysmal nocturnal haemoglobinuria (PNH) is where the immature blood stem cells are deficient in certain proteins that make it prone to destruction. A characteristic symptom is the presence of high levels of hemoglobin in the urine (hemoglobinuria) causing it to be red to brown in color in the morning.
Signs and Symptoms
Hemolytic anemia can be asymptomatic (no symptoms) for long periods especially in mild cases. The symptoms that may first be seen are the same as other types of anemia – low red blood cell levels leading to hypoxia. Once again this is dependent on the severity of the condition. More prominent symptoms are seen in cases where there is rapid and massive red blood cell destruction.
Signs and symptoms include :
- Shortness of breath
- Easily fatigued
- Chest pain
- Rapid heart rate
- Red to brown or dark yellow color of the urine
- Jaundice – yellow discoloration of the skin and eye
- Enlarged spleen and/or liver