Side Effects of Treatment: Anemia

Medically reviewed by C.H. Weaver M.D.  7/2023

Anemia is an inadequate supply of red blood cells, resulting in a decrease in the oxygen-carrying capacity of the blood. A common reason that cancer patients experience anemia is as a side effect of chemotherapy. Anemia is important because it may cause unwanted symptoms, such as fatigue, tiredness or shortness of breath, and may exacerbate or cause other medical problems, such as a heart condition. Fortunately, anemia can be effectively managed.

What is Anemia

Anemia is an inadequate supply of red blood cells, resulting in a decrease in the oxygen carrying capacity of the blood. Red blood cells contain the protein hemoglobin, which carries oxygen to all parts of the body. Low levels of red blood cells, and thus hemoglobin, cause a reduction in the amount of oxygen that can be carried to the body. 

Decreased delivery of oxygen causes the following symptoms:

• Fatigue or tiredness
• Trouble breathing
• Rapid heartbeat
• Dizziness, light-headedness, inability to concentrate, or headache
• Chest pain
• Difficulty staying warm
• Loss of sex drive
• Pale skin

Anemia commonly occurs in cancer patients, either as a direct result of the cancer or as a side effect of cancer treatment. Chemotherapy, radiation therapy and blood loss during surgery are all common causes of anemia in cancer patients. Chemotherapy drugs kill rapidly dividing cells in the body, including cancer cells and normal cells, such as cells in the bone marrow responsible for red blood cell production. Over 60% of patients treated with chemotherapy develop anemia.¹

Anemia occurs because patients can’t produce enough red blood cells or because red blood cells are lost through bleeding or destroyed faster than they can be produced. The production of red blood cells in the bone marrow is called erythropoiesis. Erythropoiesis is controlled by red blood cell growth factors. Erythropoietin is the major blood cell growth factor that increases red blood cell production in the bone marrow. Erythropoietin is produced by cells in the kidney. When kidney cells detect a decrease in tissue oxygen, erythropoietin is released into the circulation. The end result is increased red blood cell production in the bone marrow. Anemia can be prevented or corrected by using erythropoietin, or by giving a blood transfusion.

Many different causes of anemia exist. A careful evaluation is necessary to determine the cause of anemia so that the most appropriate treatment is administered.

Why is Anemia Important

1. Patients with anemia experience unwanted symptoms such as fatigue, tiredness, shortness of breath and a reduced tolerance to activity. All of these symptoms contribute to a decreased feeling of overall well-being and treatment of anemia can alleviate these symptoms.^2-4
2. Anemia may exacerbate or cause other medical problems. For example, anemia requires the heart to work harder and this additional stress to the heart could cause a heart attack in patients with preexisting heart disease.
3. Delivery of chemotherapy according to the planned dose and schedule of treatment is important to achieve the best treatment results. Anemia as a side effect of chemotherapy may prevent patients from receiving their treatment at the appropriate dose and time.

How is Anemia Diagnosed

A simple laboratory test known as a CBC, or complete blood count, measures the different types of cells in the blood. The results of a CBC indicate the amount of hemoglobin in the red blood cells. The hemoglobin count is the most useful indicator of anemia because it determines the oxygen-carrying capacity of the blood. The normal hemoglobin count is 12 g/dl – 16 g/dl for women and 14 g/dl – 18 g/dl for men. Patients with a hemoglobin count that falls below the normal range have anemia. In order to better understand the interpretation of a CBC, a sample is provided below.

Measurement of Blood Counts

A test called the complete blood count (CBC) is used to determine whether your red blood cells are low. The CBC measures the levels of the three basic blood cells: red, white, and platelets.

In the United States, the CBC is typically reported in the format shown below. If your blood counts fall outside of the normal range, which is shown in the “Reference interval” column, their values will be reported in the “Flag” column with an ‘L’ for low and an ‘H’ for high. The example CBC below shows that red blood cells are low.

Result: The result column shows counts that fall within the normal range.

Flag: Counts that are above or below the reference range are recorded in the flag column, and marked with an ‘L’ for low or ‘H’ for high.

Reference interval (or reference range): The reference interval shows the normal range for each measurement for the lab performing the test. Different labs may use different reference intervals.

White blood cells: White blood cells help protect individuals from infections. The above CBC report shows that the patient’s total white cell count is 7.2, which is within the normal range of 4.0-10.5.

Red blood cells: Red blood cells carry oxygen from the lungs to the rest of the body. The above CBC report indicates that the patient has a red cell count of 3.5. This count is lower than the normal range of 4.7-6.1, and is therefore recorded in the flag column and marked with an ‘L’ for low.

Hemoglobin (Hb or Hgb): Hemoglobin is a protein in the red cell that carries oxygen. The above CBC report indicates that the patient’s Hb count is 10.8, which is below the normal range of 14.0-18.0. The hematocrit (HCT) is another way of measuring the amount of Hb, and it is also low. This means that the patient has mild anemia and may be starting to notice symptoms. The reference ranges for hemoglobin and hematocrit will vary depending on age and gender. For women, they will be lower than those shown here. For example, the hemoglobin reference interval for a woman is 12.0-16.0.

Platelets: Platelets are the cells that form blood clots that stop bleeding. The above CBC report indicates that the platelet count for this patient is normal.

Differential: This portion of the CBC shows the counts for the 5 main kinds of white cells, either as percentages (the first 5 counts), or as the absolute number of cells (the second 5 counts).

Absolute neutrophil count: Neutrophils are the main white blood cell for fighting or preventing bacterial or fungal infections. In the CBC report, neutrophils may be referred to as polymorphonuclear cells (polys or PMNs) or neutrophils. The absolute neutrophil count (ANC) is a measure of the total number of neutrophils present in the blood. When the ANC is less than 1,000, the risk of infection increases. The ANC can be calculated by multiplying the total WBC by the percent of polymorphonuclear cells. For example, this patient’s ANC is 3.10, which equals the white blood cell count (7.2) times 43%.

How is Anemia Treated

Anemia treatment is determined by the cause of anemia and the "need" to relieve its symptoms. Anemia can be treated by increasing the hemoglobin level with blood transfusions or with erythropoietin (epoetin alfa or darbepoetin alfa), a blood cell growth factor that increases red blood cell production. The two objectives for treating anemia are to first correct the underlying cause of the anemia and second treat the symptoms of the anemia. Successful management of anemia may require erythropoietin, transfusions or both.

• Blood Transfusions - in depth

Anemia in Cancer Patients

Anemia has many causes including low iron levels, decreased folate, diseases that prevent blood cell production in the bone marrow, chronic "inflammatory" health conditions like cancer, and as a side effect of chemotherapy treatment. 

Anemia of chronic disease (ACD), also referred to as anemia of inflammatory response is common in cancer patients and is in fact a protective and natural mechanism that the human body uses to limit the amount of iron available when potentially harmful things get into our body.  When the body senses a potential threat, iron gets shuttled to ferritin to be contained so that the harmful invader cannot get to the iron. Just enough iron is made available to make red blood cells but no surplus is left to nourish harmful pathogens

Scroll to Continue

Pancreatic Cancer Treatment

Zenocutuzumab - the first approved systemic therapy for patients with NRG1 fusion–positive NSCLC or pancreatic adenocarcinoma.

Zenocutuzumab targeted therapy approved for treatment of pancreatic ductal adenocarcinoma and non-small cell lung cancer with NRG1 fusions.

By Dr. C.H. Weaver M.D.Dec 5, 2024

Lung Cancer Treatment

Immunotherapy After Chemoradiotherapy Promising in Limited-Stage Small Cell Lung Cancer

Adjuvant therapy with Imfinzi (durvalumab) significantly improved survival outcomes for patients with limited-stage SCLC

By Dr. C.H. Weaver M.D.Nov 29, 2024

Breast Cancer Treatment

Breakthrough in Understanding Tamoxifen's Effectiveness in Breast Cancer: Gut Bacteria Play a Crucial Role

Since tamoxifen is taken orally and travels through the digestive system, variations in patient responses may be connected to the gut microbiome—the trillions of bacteria in our intestines that differ significantly from one person to another.

By Dr. C.H. Weaver M.D.Nov 26, 2024

A person with ACD will experience a modest decline in hemoglobin. This will take place over time following the onset of inflammation due to the presence of the infection or disease. Hemoglobin values will generally reach a low normal range of 9.5–10.5 g/dL and remain there within this moderately low range until the underlying condition is cured.

Anemia of chronic disease is not progressive. Hemoglobin values may remain in a slightly low range, but the levels can drop to as low as 7.0 g/dL depending on the severity of the inflammation and the length of time present.

There is no treatment for anemia of chronic disease except to address the underlying condition. Iron supplementation is inappropriate in these patients because the added iron can become free to nourish bacteria and cancer cells. Taking iron pills for anemia of chronic disease could be harmful, even fatal.

Chemotherapy Induced Anemia

Erythropoietin is a blood cell growth factor that selectively increases production of red blood cells. Erythropoietin is FDA-approved for the treatment of anemia in patients with non-myeloid cancers whose anemia is a result of chemotherapy. Treatment with erythropoietin causes a gradual increase in red blood cell production. The body uses iron in red blood cell production. Thus, supplemental iron may be required to adequately support erythropoietin-stimulated erythropoiesis. Virtually all patients receiving erythropoietin therapy will eventually require supplemental iron therapy.

The two commercially available forms of erythropoietin are darbepoetin alfa (Aranesp^®) and epoetin alfa (Procrit^®, Epogen^®). Aranesp^® is a longer-acting form of erythropoietin that allows patients to receive fewer injections.

Although erythropoietin has been shown to reduce the need for blood transfusions in patients with chemotherapy-induced anemia, studies have reported serious adverse effects of erythropoietin in certain groups of patients. In response to these reports, and based on the advice of two advisory committees.

FDA Advisory on the use of Erythropoietin

The U.S. Food and Drug Administration approved revised labeling for the erythropoiesis-stimulating agents (ESAs) Procrit^® (epoetin alfa), Epogen^® (epoetin alfa), and Aranesp^® (darbepoetin alfa).

Use of ESAs to manage anemia increases hemoglobin levels and reduces the need for RBC transfusions but increases the risk of thromboembolic events. Some studies have also reported decreased survival, increased mortality during active study phase, and/or an increased risk of cancer progression or recurrence with the use of ESAs in patients with cancer.

Individuals with anemia considering the use of an ESA should discuss their risks with their recommending physician.

• ESAs may shorten your survival time or may cause your tumors to grow faster.
• ESAs should only be used to treat anemia caused by chemotherapy and not anemia from other causes in patients with cancer.
• ESAs should not be used to treat the symptoms of anemia, such as fatigue, or improve the quality of life in patients with cancer. The goal of treatment with ESAs is to avoid blood transfusions.
• Treatment with an ESA should be stopped after you complete your course of chemotherapy.
• ESAs may be considered for chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to less than 10 g/dL.
• ESAs are not generally recommended for patients with chemotherapy-associated anemia whose cancer treatment is curative in intent.
• ESAs increase the risk of thromboembolism, and clinicians should carefully weigh the risks of thromboembolism and use caution and clinical judgment when considering use of these agents.
• ESAs should be discontinued in patients who do not respond within 6 to 8 weeks.

The studies that reported increased tumor growth or decreased survival with ESAs targeted a hemoglobin level that is higher than the approved level. Nevertheless, the FDA notes that “no clinical data are available to determine whether there is a similar risk of shortened survival or increased tumor growth for patients with cancer who receive an ESA dose that attempts to achieve a hemoglobin level of less than 12 g/dL. This is the hemoglobin level commonly achieved in clinical practice.

In spite of concerns about the potential for more rapid tumor progression or shortened survival, the FDA notes: “ESA products do have an important supportive role in the treatment of patients with cancer who are undergoing chemotherapy. There is no doubt that use of ESAs in that setting reduces the need for a blood transfusion. 

Blood Transfusions

Blood transfusions rapidly replace the oxygen-carrying capacity of the blood. The goal of a blood transfusion is to increase oxygen and carbon dioxide exchange between the tissues and reduce the symptoms of anemia. However, transfusions are associated with complications. Patients should carefully consider whether to undergo a transfusion and the benefits should outweigh the risk or complications of the procedure.

Although improvements have lowered the risk of transfusion-transmitted complications, the only way to effectively eliminate the risk is to avoid exposure to allogeneic or “banked” blood. Despite the risks, red blood cell transfusions are common treatments for the severe anemia associated with cancer and chemotherapy.

Complications of Blood Transfusion

Patients receiving red blood cell transfusions are at risk for several noninfectious reactions that range from mild allergic reactions to life-threatening anaphylaxis. Clinically, the most significant complications involve impact on the immune system. However, these conditions are rare.

Infectious Complications: Patients receiving allogeneic blood are at risk for bacterial, parasitic and viral infections. Bacterial infections are estimated to occur in 1 of every 2500 blood transfusions and viral infections occur in approximately 1 in every 3000. Fear of infection with the human immunodeficiency virus (HIV) has caused the most concern, although the risk per unit of blood transfused is relatively low (1 in 225,000 transfusions). All blood components are tested for HIV antibodies; however, there is a period of time after HIV exposure before antibodies can be detected in the blood. To address this issue, intense donor screening is being used and more sensitive tests are being developed.

Patients receiving an allogeneic transfusion are at greater risk for lethal infection with the hepatitis viruses than from HIV. It is estimated that hepatitis results from approximately 1 in every 3000 transfusions.

Other Alternatives to Allogeneic Blood Transfusions

Autologous blood transfusion: A transfusion in which the patient is used as both donor and recipient is called an autologous blood transfusion. For the patient, autologous blood transfusion has no risk of infection, alloimmunization, allergic reaction or graft-versus-host disease. Autologous blood is obtained from the recipient before it is needed, which means that collection must be preplanned (e.g., before surgery or bone marrow harvest). Usually autologous blood is not collected more than once per week and no closer than 72 hours before the procedure. The autologous blood is then mixed with an anticoagulant solution and either stored for up to 42 days or frozen.

Directed donors: Directed blood donations are collected from designated donors, usually friends and family of the recipient. However, no evidence exists that directed donor blood is safer than allogeneic blood.

Tips for Dealing with Anemia

Anemia, a common condition among cancer patients, is an inadequate supply of red blood cells that results in a decrease in the oxygen-carrying capacity of the blood. Chemotherapy, radiation therapy, and blood loss during surgery are all common causes of anemia in cancer patients. Anemia is an important consideration because it may cause unwanted symptoms, such as fatigue, tiredness, or shortness of breath and may exacerbate or cause other medical problems, such as a heart condition. Furthermore, severe anemia may cause a delay in cancer treatment. If you do experience anemia during cancer treatment, there are several steps you can take to control symptoms and lessen their impact on your treatment schedule and quality of life.

The following tips will help you handle the effects of anemia:

1. If you experience any symptoms of anemia (such as fatigue, tiredness, or shortness of breath), tell your healthcare team immediately.
2. Eat a well balanced diet and drink plenty of fluids.
3. Get adequate rest.
4. Prioritize your activities so that you can participate in those that are most important and require more energy when you are feeling your best. Low-priority activities can be put off until you feel stronger.
5. Let friends and family help you with errands and regular chores so that you can conserve your energy.
6. To prevent dizziness, get up slowly from a sitting position; when you are lying down, sit up slowly before standing.
7. Consult your doctor about the risks and benefits of treatment for anemia with erythropoietin, a blood cell growth factor that increases red blood cell production. 

References:

1. Schwartzberg L, Yee L, Senecal F, et al. A Randomized Comparison of Every-2-Week Darbepoetin Alfa and Weekly Epoetin Alfa for the Treatment of Chemotherapy-Induced Anemia in Patients With Breast, Lung, or Gynecologic Cancer. The Oncologist. 2004: 9: 696-707. On-line at: theoncologist.alphamedpress.org/cgi/content/full/9/6/696
2. Amgen. Published Head-to-Head Data Show Aranesp Dosed Every Two Weeks is Comparable to Epoetin Alfa Dosed Once-a-Week. Available at: amgen.com/news/viewPR.jsp?id=647344. Accessed November 2004.
3. Razzouk BI, Hord JD, Hockenberry M, et al. Double-blind, placebo-controlled study of quality of life, hematologic end points, and safety of weekly epoetin alfa in children with cancer receiving myelosuppressive chemotherapy. Journal of Clinical Oncology. 2006;24:3583-3589.
4. Community Oncology Alliance. In the Senate of the United States. Available at: communityoncology.org/Default.aspx?tabid=68&ctl=Details&mid=386&ItemID=851. Accessed September 2007.
5. Rearden TP, Charu V, Saidman B, et al. Results of a randomized study of every three-week dosing (Q3W) of darbepoetin alfa for chemotherapy-induced anemia (CIA). Proceedings of the 40th Annual Meeting of the American Society of Clinical Oncology 2004;23:741, Abstract #8064
6. Bohlius J, Wilson J, Seidenfeld J et al. Recombinant Human Erythropoietins and Cancer Patients: Updated Meta-Analysis of 57 Studies Including 9353 Patients. Journal of the National Cancer Institute. 2006;98:708-14.
7. Straus DJ, Testa MA, Sarokhan BJ, et al. Quality-of-life and health benefits of early treatment of mild anemia. A randomized trial of epoetin in patients treated with chemotherapy for hematologic malignancies. Cancer. 2006;107:1909-1917.
8. The United States Food and Drug Administration (FDA). FDA Receives New Data on Risks of Anemia Drugs. Available at: fda.gov/bbs/topics/NEWS/2008/NEW01769.html. Accessed January 2008.
9. Mannone L, Gardin C, Quarre MC, et al. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodycplastic syndrome. Results of a phase II study. British Journal of Haematology. 2006;133:513-519.
10. Berardi R, Braconi C, Mantello G et al. Anemia May Influence the Outcome of Patients Undergoing Neoadjuvant Treatment of Rectal Cancer. Annals of Oncology. 2006;17:1661-1664.
11. Cannon J-L, Vansteenkiste J, Bodoky G, et al. Randomized, double-blind, active-controlled trial of every-3-week darbepoetin alfa for the treatment of chemotherapy-induced anemia. Journal of the National Cancer Institute. 2006;98:273-284.
12. Mancuso A, Migliorino M, De Santis S, et al. Correlation Between Anemia and Functional/Cognitive Capacity in Elderly Lung Cancer Patients Treated with Chemotherapy. Annals of Oncology. 2006; 17:146-150.
13. Freemantle N, Yao B, Calvert M, et al. Impact of Darbepoetin Alfa on Transfusion, Hemoglobin Response, and Survival in Cancer Patients with Chemotherapy-Induced Anemia: Results of a Meta-Analysis of Randomized, Placebo-Controlled Trials. Blood. 2005;106:871a, abstract #3116.
14. Amgen. FDA Approves Extended Dosing of Aranesp(R) to Treat Chemotherapy-Induced Anemia; Every-Three-Week Dosing Can Provide Added Convenience, Potentially Reducing Number of Clinic Visits and Injections for Anemia Treatment. Available at: amgen.com/media/media_pr_detail.jsp?releaseID=835699. Accessed March 2006.
15. Glaspy JA, Tchekmedyian NS: Darbepoetin alfa administered every 2 weeks alleviates anemia in cancer patients receiving chemotherapy. Oncology (Huntingt) 2002;16:23-9.
16. Mirtsching B, Beck J, Charu V, et al. Darbepoetin alfa administered every two weeks (Q2W) reduces chemotherapy-induced anemia (CIA) to the same extent as recombinant human erythropoietin (rHuEPO) but with less-frequent dosing. Proc Amer Soc of Clin Oncol 2003. Abstract 2944.
17. Vadhan-Raj S, Schreiber F, Thomas L, et al. Every-2-week darbepoietin alfa imporves fatigue and energy ratign scores in cancer patients (pts) undergoing chemotherapy. Proc Amer Soc of Clin Oncol 2003. Abstract 2942.
18. Glaspy JA, Jadeja JS, Justice G, et al. Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy. Br J Cancer 2002;87:268-76
19. Glaspy JA, Jadeja JS, Justice G, et al. A randomized, active-control, pilot trial of front-loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anemia during chemotherapy for malignant disease. Cancer 2003;97:1312-20.
20. Glaspy JA, Tchekmedyian N, Erder M, et al. Early and sustained improvement in health-related quality of life (HRQOL) was observed with frontloaded darbepoetin alfa compared to conventional therapy. Proc Amer Soc of Clin Oncol 2003. Abstract 3063.
21. Jumbe N, Heatherington A. Darbepoitin alfa rational dose/schedule evaluation based on quantitative understanding of erythropoiesis for early and sustained alleviation of anemia. Proc Amer Soc of Clin Oncol 2003. Abstract 3077.
22. Henry D, Patel R, Tchekmedyian S, et al. A phase 2 randomized study evaluating the timing of darbepoetin alfa administration relative to chemotherapy. Proc Amer Soc of Clin Oncol 2003. Abstract 3162.
23. Jadersten M, Montgomery S, Astermark J, et al. Treatment of Anemia in Myelodysplastic Syndromes with Granulocyte Colony-Stimulating Factor and Erythropoietin: Response and Impact on Survival in a Long-Term Follow-Up of 129 Patients. Blood 102:184a, 2003 (abst 643).
24. Charu V, Belani C, Gill A, et al. Every-2-Week (Q2W) Dosing of Darbepoetin Alfa in Patients with Anemia of Cancer (AOC): Interim Analysis of a Randomized, Controlled Study. Blood 102:, 499a, 2003 (abst 1816).