Hemolytic anemia

by Rosemarie Tremblay-LeMay MD FRCPC
March 3, 2022

What is hemolytic anemia?

Hemolytic anemia is a condition where the body produces antibodies that recognize and stick to red blood cells. Immune cells see the antibody-covered red blood cells and attack them. Conditions that can cause hemolytic anemia include autoimmune diseases such as lupus, blood cancers such as non-Hodgkin’s lymphoma, and chronic infections such as HIV and tuberculosis.

What are red blood cells?

Red blood cells (RBCs) are a specialized type of blood cell. RBCs are responsible for carrying oxygen from your lungs to the rest of your body and carrying carbon dioxide back to the lungs. They hold on to oxygen and carbon dioxide using a specialized protein called hemoglobin.

Normal red blood cells

Red blood cells are made in a part of the bone called the bone marrow. As young RBCs mature in the bone marrow, they produce hemoglobin. Your body needs iron in order to make hemoglobin for RBCs. Once this process is complete, the RBCs are released into the bloodstream. Normal, healthy RBCs circulate in the bloodstream for about 120 days before they are removed, and their iron is recycled to make new RBCs.

Extra iron is stored in a specialized protein called ferritin. The amount of ferritin will change as the amount of iron in your body changes. For example, a person with low levels of iron in their body will have low levels of ferritin in their blood.

What is immune hemolysis?

Red blood cells damaged by the immune system in hemolytic anemia will be either removed in the spleen or liver or destroyed in the blood. This process is called immune hemolysis.

Immune hemolysis

What are the types of hemolytic anemia?

Autoimmune hemolysis

Autoimmune hemolysis can be caused by the immune system damaging a normal part of the body. This is called an autoimmune reaction. Similarly, the antibodies that stick to RBCs can be called autoantibodies.

Some autoantibodies stick to RBCs at the normal internal temperature of the body. These autoantibodies cause a type of anemia called warm autoimmune hemolytic anemia. In contrast, some autoantibodies can only stick to RBCs at lower temperatures normally occurring in the hands and feet. These autoantibodies cause a type of anemia called cold agglutinin-mediated autoimmune hemolytic anemia.

Warm and cold agglutination

A disease called paroxysmal cold hemoglobinuria that mostly happens in children after an infection is also due to a special type of antibody that sticks to RBCs in colder temperatures of the extremities and will activate the immune system when it comes back to warmer areas of the body.

What causes autoimmune hemolysis?

There are many conditions that can lead to autoimmune hemolysis including lymphoma, infections (in particular HIV, Mycoplasma pneumoniae), and certain medications. Other autoimmune diseases such as systemic lupus erythematosus can also result in the production of antibodies against RBCs and immune hemolysis.

Alloimmune hemolysis

Immune hemolysis can also be caused when proteins not normally found in the body enter the bloodstream. Once detected by the body, the foreign proteins trigger an alloimmune reaction (“allo” means other).

An alloimmune reaction can occur when a baby inherits blood proteins (RhD or ABO) from the father that are different from the mother. An alloimmune reaction can also occur when a person receives a blood transfusion that is not compatible with their own blood group. Fortunately, both of these situations are now rare thanks to preventative medications and strict testing.

How do doctors test for immune hemolysis?

Doctors can test for immune hemolysis by looking for autoantibodies in the blood. There are two kinds of tests that can be performed to look for autoantibodies:

  • Direct antiglobulin test
  • Indirect antiglobulin test

Other blood tests can look for substances released from damaged RBCs such as indirect bilirubin and lactate dehydrogenase (LDH). A specialized protein called haptoglobin may also be measured. Haptoglobin sticks to free hemoglobin in the blood to remove it. Because the amount of free hemoglobin in the blood goes up when RBCs are damaged or destroyed inside the vessels, intravascular hemolysis causes the level of haptoglobin to go down.

When a blood sample is examined under the microscope, your pathologist may see an increased number of young (immature) RBCs. Immature RBCs are larger and more purple in color, while very immature RBCs still have a nucleus. A type of RBC called spherocyte, which is very round and darker than normal RBCs can also be seen.


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