Anemia is a condition of lower than normal levels of healthy red blood cells and their oxygen carrying component called hemoglobin. Hemoglobin in red blood cells carries oxygen from the lungs to the rest of the body. People with anemia, therefore, do not get enough oxygen delivered to the important tissues of the body. This results in many symptoms such as tiredness and weakness, and is why prolonged anemia can cause damage to the heart and other organs.

Anemia can be mild, moderate, or severe and may develop slowly over time. In many cases, anemia develops because of a nutritional problem or a chronic disease such as cancer, kidney disease, or rheumatoid arthritis. If the underlying condition or nutritional deficiency can be effectively treated, the anemia can be managed or corrected.

What Causes Anemia?

There are many reasons anemia can develop. It can result from inherited blood disorders, nutritional problems, infections, chronic diseases, menstruation, blood loss, or exposure to a drug or toxin, to name a few. Even though there are many types and causes of anemia, there are three major categories of anemia.

• Decreased Production of Red Blood Cells
  Normally, the kidneys make the hormone erythropoietin which signals the bone marrow to produce red blood cells. Many of the causes of anemia disrupt this process either by slowing erythropoietin production, damaging the bone marrow, or by not allowing the body to use building blocks needed to make red blood cells. Chronic kidney disease is the most important condition causing interruption of erythropoietin production, and as a result most patients with serious kidney disease are anemic. Iron or vitamin deficiencies can also make it hard for the body to produce healthy red blood cells. Such deficiencies can occur either from a poor diet or because the body does not properly absorb nutrients from food.


• Increased Destruction of Red Blood Cells
  If something in the body destroys or attacks red blood cells, the body tries to produce more blood. If the destruction of red blood cells is rapid, the body can't catch up. This problem is sometimes inherited, such as Sickle Cell Anemia and Thalassemia. In anemia of cancer, red blood cells also wear out faster than normal and are not replaced as quickly as they are needed.
Symptoms of Anemia
• Fatigue
• Weakness
• Pale skin
• Brittle nails
• Chest pain
• Dizziness
• Irritability
• Coldness of hands or feet
• Trouble breathing
• Fast or irregular heartbeat
• Headache
• Fuzzy thinking
• Loss of concentration
• Depression
• Loss of sex drive
• Decreased work performance
• Desire to eat ice or other peculiar things


• Blood Loss
  Severe bleeding from an accident, surgery or childbirth can result in anemia. When a lot of blood is lost within a short time, blood pressure and the amount of oxygen in the body can drop suddenly, causing severe symptoms sometimes leading to heart failure or death. The body can replace the blood that was lost, but this takes time.   
  
  Small, persistent losses of blood are a much more common cause of anemia. Bleeding from nosebleeds and hemorrhoids is easily recognized, but other causes may not be as obvious. Some less apparent sources of blood loss include ulcers in the stomach or small intestine, polyps or cancers in the large intestine, heavy menstrual bleeding, and kidney or bladder tumors, which may cause blood to be lost in the urine. Some cancers (especially digestive system cancers) can cause internal bleeding, which can lead to anemia. In addition, chronic kidney disease patients on dialysis can lose blood during treatment sessions.

People with mild anemia may have no symptoms or may not notice the symptoms because they appeared slowly. However, if the anemia is severe, the symptoms increase and become more serious. Anemic patients may feel weak, easily tired, out of breath, faint or dizzy on movement, and have problems doing the things they usually do. Other symptoms include pale skin, chest pain, irritability, numbness or coldness in the hands and feet, a fast heartbeat, and headache.  

If you’ve been feeling some of these symptoms and think you may have anemia, we recommend you see your healthcare professional. To help you tell your doctor about your symptoms which could be related to anemia, NAAC has developed an anemia Symptoms Quiz for you to fill out and take to your doctor. If you are diagnosed with anemia, there are treatments available to help. Close communication with your doctor will help him or her provide the treatment that is best for you based on what is causing the anemia.

For nearly 20 years, hematopoietic growth factors have dramatically enhanced medical treatments in the fields of hematology and oncology.  In particular, erythropoiesis-stimulating agents (ESAs) have been proven extremely effective in decreasing the need for blood transfusions, increasing hemoglobin levels, and improving the energy levels in patients with chemotherapy-induced anemia.  However, recent studies have pointed to potential risks of using ESAs to treat chemotherapy-induced and non-cancer anemia, leading to intense debate on patient safety and medicare reimbursement.

In 2003, several phase III clinical trials evaluated the safety of two commonly used ESAs: epoetin alfa (EPO) and darbepoetin alfa (DARB). These trials demonstrated a possible link to tumor progression and venous thromboembolism in anemic cancer patients receiving higher doses of ESAs or off-label use of ESAs, prompting the Oncologic Drugs Advisory Committee (ODAC) of the Food and Drug Administration (FDA) to review and update the safety profiles of EPO and DARB in 2004. 

Additional clinical studies in 2006 and 2007 identified further safety concerns with EPO and DARB, including increased patient mortality, prompting the FDA to add a “black box” warning to the label.  In May of 2007, ODAC issued a report that urged caution with off-label use and careful consideration of the risks and benefits of ESA dosing.

Safety concerns continued following a 2007 statement to health care professionals by the ESA manufacturer, Amgen, which detailed an unpublished clinical study in which patients were found to have a higher mortality rate after treatment with DARB.  Because of this letter and increased attention from the FDA, private payers and the Center for Medicare and Medicaid Services modified reimbursement policies to cover fewer types of cancer patients and only those with increasingly severe anemia. These drastic provisions have been criticized by health care providers who feel that patients may be short-changed by “reactive policies” that are lacking proper justification through published, peer-reviewed studies.

For example, studies have demonstrated that a hemoglobin level between 11 and 13 g/dL is needed to prevent fatigue. However, because treatment thresholds have been lowered to less than 10 g/dL of hemoglobin, many cancer patients will experience fatigue and functional dependence.  This problem is compounded by the denial of ESAs for patients with certain types of cancer-related anemia and for patients more than eight weeks removed from chemotherapy. 

Although policy changes and unpublished research findings seem to further complicate the ESA dosing debate, physicians and payers alike have stepped up efforts to quell the controversy.  Many physicians recommend strict adherence to the current FDA label and dosing guidelines that have been based on peer-reviewed research. In addition, physicians and policy makers have recommended research to explore safety risks of off-label ESA use before insurance organizations permanently enact policies that may be too restrictive. 

Although economic costs are a large concern when developing medical policy, many physicians agree that patient safety should remain paramount in any debate regarding ESA dosage. Clearly, additional research and proper analysis are required in order to ensure that patient’s medical needs are consistently served.