Anemia

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Anemia

Description

Anemia is characterized by an abnormally low number of red blood cells in the circulating blood. It frequently affects patients with cancer. In fact, in many cancer diagnoses such as multiple myeloma and acute leukemia , the presence of anemia may be what initially prompts a doctor to suspect an underlying tumor (neoplasm). Whether or not anemia develops depends on the type of cancer found, the treatment employed, as well as the presence or absence of other underlying medical disorders.

Symptoms of malignancy-associated anemia may range from weakness, pallor, and fatigue to shortness of breath and increased heart rate. Symptoms of anemia can compromise a patient's ability to tolerate treatment, and may severely interfere with activities of daily living. Anemia may be particularly problematic in older individuals with cancer. The incidence and severity of anemia tends to increase as the cancer progresses.

Blood is comprised of three major cell types: white blood cells, which help the body fight infection; platelets, which help the blood to clot when necessary; and red blood cells, which transport oxygen from the lungs to the tissues in the body, and then transport carbon dioxide from those tissues back to the lungs. This exchange is enabled by the most important component of red blood cells—the protein called hemoglobin that binds easily to oxygen and carbon dioxide.

Red blood cells are produced in the bone marrow through a process called erythropoiesis. When the bone marrow functions normally, it continuously replaces red blood cells to maintain a normal level that allows for adequate oxygenation of the tissues. The hormone erythropoietin stimulates red blood cell production and sends a message to the bone marrow to increase production when oxygen levels in the body are low. This mechanism is often impaired in patients with cancer.

Causes

The causes of anemia are multifactorial, and often those factors act in conjunction with one another. Generally, anemia may result from a direct effect of a cancerous tumor, or from an indirect effect of the tumor. The cancer process may directly cause anemia through two main mechanisms: blood loss or bone marrow replacement. However, most cases of anemia in cancer patients result from the indirect effects of the cancer.

Direct effects of the tumor

Anemia is a frequent complication of cancers due to bleeding. Cancers of the head and neck, the gastrointestinal and genitourinary system, and the cervix are frequently associated with endogenous bleeding, or bleeding that occurs outside the body. Bleeding occasionally develops within the tumor itself, particularly in sarcomas , melanomas, and ovarian and liver carcinomas.

A second direct cause of anemia in cancer is bone marrow replacement, which inhibits the body's ability to appropriately produce red blood cells. Certain cancers, such as acute leukemia, lymphoma and myeloma , directly suppress bone marrow function, thereby causing anemia. Other types of cancer, such as prostate or breast cancer , often spread to the bone marrow, inhibiting red blood cell production by actually replacing the bone marrow itself.

Indirect effects of the tumor

Anemia of chronic disease, also called anemia of malignancy, is the most common type of anemia seen in individuals with cancer. It is a diagnosis made only after other possible causes are ruled out and if very specific conditions are met. The presence of low levels of iron coupled with normal levels of storage iron helps distinguish anemia of chronic disease from iron deficiency anemia. Factors that cause anemia of chronic disease are not entirely clear. However, it is believed that cytokines (non-antibody proteins) produced by the tumor reduce production of and impair responsiveness to erythropoietin. Typically, this type of anemia develops slowly. Rapid development of anemia may indicate another cause.

Treatments used to manage cancer have been implicated in the development of anemia in cancer patients. Radiation therapy to large areas of bone marrow, as in the hip area, may suppress bone marrow function and lead to anemia. Chemotherapy can also cause bone marrow suppression, some drugs by specifically targeting red blood cell production. Studies have shown that 10 to 40% of patients taking cisplatin develop significant anemia. Cisplatin, a chemotherapy drug with potentially toxic effects to the kidneys, is believed to reduce the production of the hormone erythropoietin in the kidneys. Although most treatment-induced bone marrow suppression is short term, there is some evidence to support the possibility of long-term problems with blood cell production.

Treatment can increase the risk of anemia in other ways. Chemotherapy, for example, causes bone marrow suppression that may reduce the immune system's ability to fight off opportunistic infection. The resulting infections can impact the bone marrow's functioning, possibly leading to the development of anemia.

Hemolytic anemia is a type of anemia in which the red blood cell has a shortened lifespan (normal lifespan is 90-120 days). Because the bone marrow is not able to compensate by producing more red blood cells, anemia results. Abnormalities in the red blood cells may be intrinsic or may be caused by environmental factors such as auto-antibodies to red blood cells or damage from chemotherapy.

Although one factor may have a greater influence, it is important to realize that several factors may be causing anemia. For example, approximately 70% of patients with multiple myeloma are anemic at the time of diagnosis. Anemia in these cases is caused by a combination of mechanisms including bone marrow replacement with cancer cells, bone marrow suppression from chemotherapy, and impaired production of erythropoietin.

Treatments

Treatment of the anemia is directed at the underlying cause. In many cases, treating or removing the cancer corrects the red blood cell deficit. Management of autoimmune hemolytic anemia, which can be associated with chronic lymphocytic leukemia , may range from the administration of corticosteroids to the surgical removal of the spleen. More commonly, cancer-related anemias are treated with blood transfusions and/or a drug called epoetin alfa.

Blood transfusions

Blood transfusions have been the principle treatment for anemia for many years. Until the 1960s, only whole blood was given. Then, methods of separating whole blood were devised, allowing only particular components, such as platelets, red blood cells, or plasma, to be transfused.

Blood transfusions are not without risk, and must be used carefully. Many patients react to the white blood cell antigens by developing a fever . This is so common that patients are routinely premedicated to prevent fever from developing. Individuals with long-term transfusion needs, such as patients with leukemia, may be given blood products with a reduced number of white blood cells to reduce the risk of sensitization to transfused blood.

Cytomegalovirus (CMV) is a virus that may be present in blood products. Although it has no effect on individuals with normally functioning immune systems, cancer patients often have a diminished ability to fight infection. These patients may be at risk for CMV if they are CMV negative and receive CMV-positive blood.

Transfusion-associated graft-versus-host disease (TA-GvHD) is another risk factor associated with blood transfusions in cancer patients. Although it is very rare, it is often fatal. With TA-GvHD, the patient's immune system does not recognize the white blood cells in the donor blood as "nonself." The donor white blood cells, however, recognize the patient as "nonself, " and an immune-mediated reaction ensues. To prevent this reaction in at-risk patients, blood may be irradiated prior to transfusion.

Epoetin alfa

As mentioned previously, erythropoietin is a protein produced in the kidneys that stimulates red blood cell production. Using DNA technology, this hormone has been replicated to create the drug epoetin alfa for the treatment of anemia in select cancer patients. (The drug is also called erythropoietin. ) The use of this drug in the cancer setting has shown great promise, both in the treatment of cancer-related anemia, and in the reduction in the need for blood transfusion.

However, epoetin alfa therapy is not advisable for everyone. This drug is not recommended for use in cancer-related anemia caused by bleeding, hemolysis, or iron deficiencies. Nor is it recommended for patients with hypertension or albumin sensitivity. Because no human studies are available to determine its effect on a fetus, women taking epoetin alfa should take measures to prevent pregnancy.

Cancer patients with anemia who are undergoing chemotherapy may benefit from this drug. Studies have shown an increased hematocrit (the volume percentage of red blood cells in whole blood) level and a decreased need for blood transfusions after the first month of therapy in this population. Epoetin alfa is injected three times a week, and throughout therapy, blood cell counts are monitored closely.

Resources

BOOKS

Abeloff, M., et al. (Eds.) "Hematopoietic Dysfunction by Hematologic Lineage." In Clinical Oncology, 2nd Ed. New York: Churchill Livingstone Publishers, 2000.

Lee, G. and C. Bennett (Eds.) "Nonmetastatic Effects of Cancer: Other Systems." In Cecil Textbook of Medicine, 21st Ed. Philadelphia, PA: W. B. Saunders Co., 2000.

Lee, G., et al. (Eds.) Wintrobe's Clinical Hematology. Baltimore, MD: Williams & Wilkins Publishing, 1999.

Varricchio, C., (Ed.) "Cytopenias." In A Cancer Source Book for Nurses Atlanta: Jones and Bartlett Publishers, 1997, pp.161-73.