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Medically reviewed by C.H. Weaver M.D. 11/2022

Diagnosing and treating anemia is important to feeling your best when living with a myeloproliferative neoplasm (MPN). 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 in most patients.

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.

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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

What Causes Anemia in MPN Patients?

Anemia may have more than one cause which can be related or unrelated to a MPN. 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 result is increased red blood cell production in the bone marrow.

  • Myelofibrosis and other MPN’s can cause anemia directly by crowding out healthy cells in the bone marrow and interfering with normal blood cell production.
  • Anemia can occur as a direct result of MPN treatment. Chemotherapy, radiation therapy and blood loss during surgery are all common causes of anemia. Anti-cancer drugs kill rapidly dividing cells in the body, including \ normal cells in the bone marrow responsible for red blood cell production. Over 60% of patients treated with chemotherapy develop anemia. Hydroxyurea and Jakafi which are commonly used to treat MPN’s can cause anemia.1,11
  • Nutritional Deficiency such as iron, vitamin B12, or folic acid can cause or contribute to anemia. These nutrients are all required to produce healthy red blood cells.

Why is Anemia Important?

· 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

  • 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.
  • 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 complete blood count (CBC), 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.

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 blood cell growth factors or maturation agents 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 a growth factor, transfusions, or both.

Medications

  • Erythropoietin (epoetin alfa or darbepoetin alfa).1-6,7
  • Androgens (synthetic male hormones)
  • Rebolzyl: The U.S. Food and Drug Administration (FDA) has approved Reblozyl® (luspatercept-aamt), the first and only erythroid maturation agent (EMA), for the treatment of anemia in patients with MDS failing an erythropoiesis stimulating agent.
  • MPN treatments, such as combination therapy with JAK inhibitors, may improve anemia.10

Nutritional Supplements

If a nutritional deficiency is a partial cause of a person’s anemia, supplementing those nutrients can often help. Folic acid, B12, and Iron can all be replaced with supplements. Always talk with your doctor before trying a new nutritional supplement.

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 may also be associated with complications.

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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.9

Anemia in Cancer Patients

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

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 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.8

Tips for Dealing with Anemia

If you 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:

  • If you experience any symptoms of anemia (such as fatigue, tiredness, or shortness of breath), tell your healthcare team immediately.
  • Eat a well-balanced diet and drink plenty of fluids.
  • Get adequate rest.
  • 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.
  • Let friends and family help you with errands and regular chores so that you can conserve your energy.
  • To prevent dizziness, get up slowly from a sitting position; when you are lying down, sit up slowly before standing.
  • 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.
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References:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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
  7. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-erythropoiesis-stimulating-agents-esa-epoetin-alfa-marketed-procrit-epogen-darbepoetin
  8. 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).
  9. National Heart Lung and Blood Institute. What are the risks of a blood transfusion? Available at: Accessed February 11, 2020.
  10. Gupta V, Verstovsek S, Mesa R, et al. Long-term outcomes of Jakafi (RUX) therapy in patients (pts) with myelofibrosis (MF): 5-year update from COMFORT-I. Proceedings from the 2016 annual meeting of the American Society of Clinical Oncology (ASCO). Abstract #1712.
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665047/