Anemia Due to Malignancy

Why cancer causes anemia

Anemia in cancer usually has more than one cause at the same time.

Anemia of inflammation

Cancer triggers inflammatory signals (such as interleukin-6) that raise hepcidin, a hormone that locks iron inside storage cells, so the bone marrow cannot use it even when stores are normal. Inflammation also blunts the kidney's production of erythropoietin, the hormone that drives red cell production. This is called anemia of chronic disease or functional iron deficiency.

Blood loss

Tumors of the stomach, bowel, bladder, kidney and uterus can bleed slowly, leading to iron deficiency anemia. Unexplained iron deficiency in an adult, especially a man or a woman after menopause, is a classic reason to check for colorectal cancer.

Bone marrow involvement

Cancers of the blood and marrow, such as leukemia, multiple myeloma, lymphoma and myelodysplastic syndrome, crowd out normal blood production. Solid tumors such as breast, prostate and lung cancer can also spread to the bone marrow.

Cancer treatment

• Chemotherapy damages rapidly dividing marrow cells, with anemia often worst several weeks into treatment. Platinum drugs such as cisplatin also affect the kidneys.
• Radiation to large areas of bone marrow, such as the pelvis or spine.
• Targeted therapies and immunotherapy occasionally cause autoimmune hemolysis.

Other causes

• Poor nutrition with low iron, vitamin B12 or folate
• Chronic kidney disease
• Hemolysis (red cell destruction), linked to some lymphomas and leukemias
• Surgery and blood draws

Symptoms

Symptoms depend on how low and how fast the hemoglobin falls:

• tiredness and weakness, often described as cancer fatigue
• shortness of breath, especially on exertion
• dizziness, lightheadedness and headaches
• a fast or pounding heartbeat
• pale skin, gums or nail beds
• feeling cold
• difficulty concentrating
• chest pain in people with heart disease

Because cancer itself causes fatigue, anemia is easily overlooked. A blood count helps tell them apart.

Diagnosis

• Complete blood count (CBC): hemoglobin, red cell size (MCV) and other blood cells
• Reticulocyte count: shows whether the marrow is responding
• Iron studies: ferritin, transferrin saturation. In cancer, ferritin may be normal or high despite functional iron deficiency, so transferrin saturation is important
• Vitamin B12 and folate
• Kidney function
• Hemolysis tests: bilirubin, LDH, haptoglobin, Coombs test
• Stool tests or endoscopy for bleeding
• Bone marrow biopsy if marrow involvement is suspected

Treatment

The choice depends on the cause, the severity, symptoms and the goals of cancer treatment.

Treat the underlying cause

Stopping bleeding, treating the cancer and correcting deficiencies are first steps.

Iron

• Intravenous iron is often preferred in cancer, because inflammation blocks absorption of oral iron. It is recommended for absolute iron deficiency and for functional iron deficiency, especially alongside ESAs.
• Oral iron can work for straightforward iron deficiency with mild inflammation.

Vitamin B12 and folate

Replaced if low.

Red blood cell transfusion

Gives fast relief for severe or symptomatic anemia. Guidelines generally consider transfusion when hemoglobin falls below about 7 to 8 g/dL, or at higher levels with symptoms or heart disease. Each unit raises hemoglobin by about 1 g/dL. Risks include reactions, fluid overload and iron overload with repeated transfusions.

Erythropoiesis-stimulating agents (ESAs)

Epoetin alfa and darbepoetin mimic erythropoietin. ASCO and ASH guidelines recommend considering them for people receiving chemotherapy with non-curative intent whose hemoglobin is below 10 g/dL, after discussing risks. ESAs increase the risk of blood clots and stroke, and in some cancers may shorten survival or speed tumor growth, so they are generally avoided when cancer treatment aims at cure and are used at the lowest effective dose.

Living with cancer-related anemia

• Pace activities and rest between tasks.
• Eat a balanced diet with protein and iron-rich foods if appetite allows.
• Stand up slowly to avoid dizziness.
• Report increasing breathlessness, chest pain or bleeding promptly.
• Gentle exercise as tolerated reduces cancer fatigue.

Outlook

Anemia often improves after chemotherapy ends, usually over a few months, and when the cancer responds to treatment. Anemia from marrow involvement or advanced cancer may need ongoing transfusions. Treating anemia improves energy and quality of life, and in some cases allows cancer treatment to continue on schedule.

Frequently asked questions

Why does cancer cause anemia?

Cancer causes anemia through inflammation that blocks iron use and lowers erythropoietin, bleeding from tumors, cancer cells crowding the bone marrow, kidney damage and poor nutrition. Chemotherapy and radiation also suppress red cell production. Most people have more than one cause.

Is anemia a sign of cancer?

It can be. Unexplained iron deficiency anemia, especially in men and women after menopause, can be a sign of bowel or stomach cancer. Anemia with low platelets or abnormal white cells can suggest a blood cancer. Most anemia has other causes, but unexplained anemia should be investigated.

How long does chemotherapy-induced anemia last?

It usually develops during treatment and improves over several weeks to a few months after chemotherapy ends, as the bone marrow recovers. Recovery can take longer after intensive treatment or radiation to large areas of bone.

When do cancer patients need a blood transfusion?

Transfusion is usually considered when hemoglobin drops below about 7 to 8 g/dL, or at higher levels if there are symptoms such as breathlessness, chest pain or severe fatigue, or heart disease. Your cancer team weighs symptoms, blood counts and treatment plans.

Are ESAs safe for cancer patients?

ESAs can reduce the need for transfusion but raise the risk of blood clots and stroke and may affect tumor growth in some cancers. Guidelines limit them mainly to people having chemotherapy that is not aimed at cure, with hemoglobin below 10 g/dL, after a careful discussion of risks.