Erythropoietin (EPO) is a hormone produced by the kidneys that helps in the production of red blood cells (RBCs). EPO enters the bone marrow from the blood — the site of RBC production — whenever there is a drop in blood oxygen levels.

EPO in cold agglutinin disease

Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA) in which the body produces antibodies called cold agglutinins when exposed to cold temperatures (32 to 50 degrees Fahrenheit). These cold agglutinins bind to RBCs and disintegrate them, a biological event called hemolysis, causing anemia.

The administration of EPO could help the body produce more RBCs to compensate for their loss in severe forms of CAD. There are several EPOs available to treat the anemic conditions caused by CAD. These include Procrit, Epogen, and Aranesp.

How EPO works

The exact mechanism by which EPO works in CAD treatment is still being investigated. It is thought that EPO works in reducing the effects of anemia in two ways:

  • EPO enters the bone marrow and stimulates the production of RBCs through a process known as erythropoiesis. This raises the level of hemoglobin in the blood. Hemoglobin is required to carry oxygen to the cells and tissues in the body.
  • EPO decreases the total autoantibodies present in the blood, consequently increasing the overall RBC concentration.

The administration of EPO may reduce the need to undergo a blood transfusion. However, it takes about two to six weeks for a perceivable increase in RBC counts.

EPO in clinical trials

There are not enough studies to either support or discourage the use of EPO for the treatment of CAD. EPO therapy is widely used as supportive therapy for CAD in North America but not so much in Europe.

EPO therapy was found to be effective in increasing hemoglobin levels and reticulocyte (immature RBCs) counts in two patients diagnosed with AIHA associated with relative reticulocytopenia, the reduction in the number of reticulocytes in the blood. These patients were already on immunosuppressive medication and blood transfusions proved to be ineffective.

Another small prospective clinical trial involving 12 patients with warm and cold type AIHA showed favorable results without any major adverse effects. The patients had varying clinical history, but all showed a significant increase in hemoglobin levels and reticulocyte counts one to two weeks after EPO therapy.

Other information

EPO therapy is not recommended for people with cancer and heart problems. EPO can also cause blood clots and patients might need to be administered blood thinners to decrease the risk of clot formation during or after surgery.

In some cases, the body may make antibodies to EPO, which further increases the severity of anemia. Allergies and skin reactions are also possible. Pregnant and breastfeeding women should not use EPOs stored in multi-dose vials as they contain benzyl alcohol that can be harmful to the fetus and newborn.


Last updated: Aug. 14, 2019


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