1/24/2018 Defining and recognizing different types of anemia common to the oncology practice

Defining and recognizing different types

of anemia common to the oncology
practice
August 3, 2011

Throughout their careers, hematologists and oncologists will likely be exposed to

many patients with anemia, the most commonly occurring blood disorder
associated with systemic diseases.1 Although there are many forms of anemia,
defined as a decrease in circulating red blood cells,2,3 the pathophysiologic origins
of the condition are grouped into only three categories.2 First, anemia can be
caused by a decrease in the production of normal and functioning red blood cells.
Second, anemia can be caused by the destruction of red blood cells and, finally,
anemia can be the result of blood loss.2

Hematologists and oncologists are exposed to patients with anemia from all of
these pathophysiologic origins. Therefore, the ability to recognize the signs and
symptoms of the condition and understand the etiology and pathophysiology behind
it are important for the recommendation of appropriate management.2 Additionally,
critical to recognizing signs and symptoms is informing patients early on about
anemia so that patients are empowered to take an active role in their care and
inform the physician of their status.

Etiology of anemia in cancer patients

Recognizing and treating anemia in cancer patients can be challenging because

the origin of the condition may be multifactorial.2

Anemia in a patient with cancer may be the result of the malignancy itself, the
treatment prescribed for the malignancy, or an unassociated underlying condition.
Suppression of the production of red blood cells can be caused by cancer cells
infiltrating bone marrow or by myelotoxic chemotherapeutic agents. Anemia due to
the destruction of red blood cells can occur due to inflammatory cytokines produced
by the tumor, or hemolysis2 from chemotherapeutic agents such as oxaliplatin,
fludarabine and interferon.4

Anemia can also occur as a result of acute or chronic blood loss, nutritional
deficiencies—not uncommon in cancer patients—and hemolysis or inflammatory
cytokines associated with chronic disease.5 In addition, a poor functional status,6
low hemoglobin (Hb) at baseline, history of radiation to more than 20% of the body,
history of transfusion,7 older age,8 weight loss,9 metastatic disease, prior

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1/24/2018 Defining and recognizing different types of anemia common to the oncology practice

myelosuppressive therapy, pulmonary disease6 and comorbid cardiac disease2 are

all risk factors that increase the likelihood of a patient developing anemia during
cancer treatment.

Finally, anemia can also be related to patient characteristics that are not necessarily
connected to the cancer or cancer treatment at all.2 Sickle cell anemia and
thalassemia are two types of inherent anemia present since birth. In some cases
where an individual already has anemia, a cancer diagnosis can compound the
severity of the anemia.2,9,10

Signs and symptoms

Although a low Hb level may be the first indication of anemia, it should prompt
physicians to conduct a thorough patient history and physical examination. On a
broader level, the health care provider should ask the patient about the onset and
duration of symptoms, family medical history, comorbidities and any medications he
or she is currently taking.2

An examination for more specific symptoms is also necessary as a decrease in red

blood cell levels, which diminishes the oxygen-carrying capacity of the blood, can
ultimately lead to hypoxia and hypoxemia, eventually having an effect on multiple
biological and organ systems.9,11,12 These effects will manifest as certain
recognizable signs and symptoms of anemia including fatigue, lethargy, shortness
of breath, pallor of the skin, heart palpitations, and soft systolic murmurs.13

However, symptoms can vary greatly because anemia can affect so many different
organ systems, including the neurological system (eg, fatigue, sleep disorders,
impaired cognitive function, depression), immune system (eg, impaired T-cell and
macrophage function), cardiorespiratory function (eg, tachycardia, palpitations,
dyspnea) and more (eg, pallor of the skin, fluid retention). Patients may exhibit
genitourinary symptoms that include a loss of libido or menstrual problems, or they
could exhibit gastrointestinal symptoms such as anorexia, nausea, or irregular
bowel movements.11,12

Hemoglobin

Anemia is commonly a manifestation of another underlying problem.2,14 The

National Comprehensive Cancer Network anemia guideline panelists agreed in
their recommendations that a drop in Hb to below 11 g/dL should prompt further
evaluation;2 however, the ability of the patient to tolerate a decline in Hb level is
relative to each patient’s “normal” Hb levels.2,7

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1/24/2018 Defining and recognizing different types of anemia common to the oncology practice

According to the National Cancer Institute and

the National Institutes of Health, anemia can be
classified into five grades. Grade 1, considered
mild anemia, is Hb from 10 g/dL to the lower
limit of normal; grade 2 anemia, or moderate
anemia, is Hb from 8 to less than 10 g/dL; grade
3, or severe anemia, is below 8 g/dL; grade 4, is
life-threatening anemia; grade 5 is death
(Table).13 In addition, Hb levels can vary
according to a patient’s gender and
race/ethnicity, with Hb levels 1 to 2 g/dL lower in
women.15

When a hematologist or oncologist is confronted

with a patient that may have anemia, a good
history, physical exam and laboratory workup
are important to not only confirm anemia but
also to identify the type of anemia.2

Laboratory testing

To help define the type of anemia, there are multiple laboratory tests that can be
used. Hb and hematocrit (Hct) levels can be checked by conducting frequent
complete blood counts, which also test mean corpuscular volume (MCV).9

The MCV measures the average volume of a red blood cell. The measurement of
MCV is classified into three categories: microcytic (< 80 fL), normocytic (80-100 fL)
and macrocytic (> 100 fL).2

Microcytic anemia is commonly the result of iron deficiency but could also be due to
thalassemia. A normocytic MCV measurement may indicate anemia due to
hemorrhage, bone marrow failure, anemia of chronic inflammation or renal
insufficiency.2 Finally, macrocytic MCV usually indicates anemia due to a vitamin
B12 or folate deficiency,2 but can also indicate a primary marrow synthetic
abnormality as would occur in myelodysplasia.15

In addition, the cause of anemia can be narrowed by examining a patient’s

peripheral blood smear. Learning and gaining familiarity with different types and
morphologies of damaged red blood cells may aid in the diagnosis of anemia.2 For
example, if the smear shows the presence of spherocytes and an increased
reticulocyte count, the patient may have hemolytic anemia.16

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Finally, the underlying cause of anemia can be narrowed further by ordering a stool
guaiac test, which helps rule out blood loss, or a bone marrow biopsy, which helps
to identify metastatic disease and hematologic malignancies.2,9

References

1. Spivak JL. The blood in systemic disorders. Lancet. 2000;355:1707-1712.

2. he NCCN Clinical Practice Guidelines in Oncology. Cancer- and Chemotherapy-
Induced Anemia. Version 2.2012. National Comprehensive Cancer Network
website. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
Accessed August 5, 2012.
3. National Cancer Institute. Dictionary of cancer terms. National Cancer Institute
website. http://www.cancer.gov/dictionary. Accessed June 20, 2011.
4. Klap PC, Hemphill RR. Acquired hemolytic anemia. In: Tintinalli JE, Stapczynski
JS, Cline DM, Ma OJ, Cydulka RK, Meckler GD, eds. Tintinalli’s Emergency
Medicine: A Comprehensive Study Guide. 7th ed. New York, NY: McGraw-Hill;
2011. http://accessmedicine.com/content.aspx?aid=6386652. Accessed February
21, 2011.
5. Schwartz RN. Anemia in patients with cancer: incidence, causes, impact,
management, and use of treatment guidelines and protocols. Am J Health Syst
Pharm. 2007;64(suppl 2):S5-S13.
6. Shelton BK. Therapeutic options for patients with cancer and treatment-related
anemia. Adv Stud Nurs. 2006;4:109-114.
7. Hurter B, Bush NJ. Cancer-related anemia: clinical review and management
update. Clin J Oncol Nurs. 2007;11:349-359.
8. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of
anemia in persons 65 years and older in the United States: evidence for a high
rate of unexplained anemia. Blood. 2004;104:2263-2268.
9. Adamson JW, Longo DL. Anemia and polycythemia. In: Fauci AS, Braunwald E,
Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. New
York, NY: McGraw Hill; 2008:353-363.
10. Guyton AC, Hall JE. Red blood cells, anemia, and polycythemia. In: Guyton AC,
Hall JE, eds. Textbook of Medical Physiology. 11th ed. Philadelphia, PA: Elsevier
Saunders; 2006:419-428.
11. Ludwig H, Fritz E. Anemia in cancer patients. Semin Oncol. 1998;25(suppl 7):2-6.
12. Ludwig H, Strasser K. Symptomatology of anemia. Semin Oncol. 2001;28(suppl
8):7-14.
13. US Department of Health and Human Services. National Institutes of Health.
National Cancer Institute. Common terminology criteria for adverse events
(CTCAE). Version 4.0. National Cancer Institute website.

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http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. Published May 28, 2009. Accessed June 9, 2011.
14. Hinkel JM, Li EC, Sherman SL. Insights and perspectives in the clinical and
operational management of cancer-related anemia. J Natl Compr Canc Netw.
2010;8(suppl 7):S38-S55.
15. Tefferi A, Hanson CA, Inwards DJ. How to interpret and pursue an abnormal
complete blood cell count in adults. Mayo Clin Proc. 2005;80:923-936.
16. Marks PW, Rosenthal DS. Hematologic manifestations of systemic disease:
infection, chronic inflammation, and cancer. In: Hoffman R, Benz EJ, Shattil SJ, et
al, eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, PA:
Churchill Livingstone Elsevier; 2009; 2309-2319.

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