August 03, 2011
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Defining and recognizing different types of anemia common to the oncology practice

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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 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

TableAnemia 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

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

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. 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.