COLUMBIA, South CarolinaAnemia 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 (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
"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.
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.