COLUMBIA, South Carolina—Anemia impairs quality of life and functional status, can interfere with cancer therapies, and now seems linked to poorer prognosis and shortened life span, at least in some cancer patients, according to Robert E. Smith, Jr., MD, president of South Carolina Oncology Associates and clinical associate professor at the University of South Carolina School of Medicine in Columbia. In his experience, and that of other oncologists, recombinant human erythropoietin(Drug information on erythropoietin) (rHuEPO) and darbepoetin alfa (Aranesp) can increase hemoglobin levels, decrease fatigue, and improve quality of life for cancer patients. To get optimal treatment results with erythropoietic agents, however, requires understanding the full range of etiologies of anemia and its signs and symptoms, and a thorough work-up of patients.
"Anemia is not a diagnosis, except in those few cases where there’s an inborn or acquired red blood cell abnormality, but in most cases, it’s a sign of an underlying pathology," Dr. Smith explained. Anemia is due either to decreased effective life span of red blood cells or bone marrow that responds inadequately to erythropoietin so that production of red blood cells is impaired.
The underlying causes of anemia (see Figure 1) include impaired ability of the kidneys to produce erythropoietin due to antibiotics, other toxins, or the myelosuppressive effects of chemotherapy and radiation, and decreased sensitivity of EPO due to inflammatory cytokines or replacement of bone marrow by cancer or fibrosis. Other etiologies include nutritional deficiencies (iron, B12), hemolysis, and blood loss. The diagnosis of anemia of chronic disease is often made by eliminating other causes.
Anemia of chronic disease is characterized by a deficiency in EPO
production and a bone marrow that fails to properly respond to EPO.
According to current belief, Dr. Smith said, reduced EPO production results
from a blunted EPO response rather than a quantitative deficiency.
The secondary release of cytokines can also suppress EPO production
in cancer patients. One study showed that interferons suppress
erythroid-myeloid precursors in bone marrow.
The work-up of the patient should include questions about cancer treatment as well as other toxic exposures. How much chemotherapy and/or radiation has the patient received? Prior blood work should be reviewed to determine if there was an abrupt fall in the red blood cell count that might indicate bleeding or hemolysis, or a more gradual trending down over several months. During the physical exam, the physician should look for signs of wasting, splenomegaly, and venous engorgement.
Laboratory Tests
Lab work should include a CBC with indices, a reticulocyte count to look for indications of bleeding or hemolysis, and indirect bilirubin that might indicate hemolysis. The blood smear should be reviewed "for spherocytes that might indicate a hemolytic process, fragmented red blood cells that might indicate disseminated intravascular coagulation or a microangiopathic process going on, nucleated red blood cells that would tip you off that there may be fibrosis or extensive tumor replacing bone marrow, and things like rouleaux that might indicate a paraprotein," Dr. Smith said. He did not include erythropoietin levels in the list of lab test measurements because the levels usually do not affect the decision-making process in the case of anemia of chronic disease, he said.
