Anemia

How anemia works

Red blood cells are made in the bone marrow under the control of erythropoietin, a hormone made by the kidneys. Each cell lives about 120 days and carries oxygen bound to hemoglobin. Making hemoglobin needs iron, and making new cells needs vitamin B12 and folate.

Anemia develops when one of three things happens:

1. Blood loss: acute (injury, surgery, gut bleeding) or chronic (heavy periods, slow bleeding from the stomach or bowel)
2. Decreased production: lack of iron, B12 or folate, kidney disease, chronic inflammation, or bone marrow failure
3. Increased destruction (hemolysis): red cells are broken down faster than the marrow can replace them

Symptoms of anemia

Symptoms depend on how low hemoglobin is and how fast it fell. Slowly developing anemia can be surprisingly well tolerated.

• Fatigue, weakness and reduced exercise tolerance
• Pale skin, pale inner eyelids, nail beds and gums
• Breathlessness on exertion
• Fast heartbeat or palpitations
• Dizziness, especially when standing up
• Headaches, poor concentration and irritability
• Cold hands and feet
• Chest pain (angina) or ankle swelling in people with heart disease

For a practical look at what these signs mean and what to do after a low blood test result, see signs of anemia.

Types of anemia

Doctors classify anemia by the size of the red cells (mean corpuscular volume, MCV), which narrows the cause quickly.

Iron deficiency anemia

Iron deficiency anemia accounts for about half of all anemia. Common causes are heavy periods, pregnancy, low-iron diets, poor absorption from celiac disease or gastric surgery, and gut bleeding from ulcers, NSAIDs, polyps or bowel cancer. Clues include brittle or spoon-shaped nails, sore tongue, hair loss and pica (craving ice or non-food items).

Vitamin B12 and folate deficiency

Vitamin B12 deficiency is often caused by pernicious anemia, an autoimmune condition that blocks B12 absorption. Other causes are vegan diets, long-term metformin or acid-reducing medicines, and bowel surgery. It can damage nerves, causing numbness, unsteadiness and memory problems. Folate deficiency comes from poor diet, alcohol, pregnancy and some medicines.

Anemia of chronic disease

Anemia of chronic disease, or anemia of inflammation, occurs with rheumatoid arthritis, inflammatory bowel disease, chronic infections and cancer. The hormone hepcidin traps iron in storage so the marrow cannot use it.

Anemia of chronic kidney disease

Failing kidneys make less erythropoietin. Anemia due to chronic kidney disease becomes common as kidney function falls and is treated with iron and, when needed, erythropoiesis-stimulating agents (ESAs).

Hemolytic anemias

In hemolytic anemia, red cells are destroyed early. Causes include autoimmune disease, inherited conditions such as G6PD deficiency and hereditary spherocytosis, infections, some medicines, and mechanical damage from heart valves. Jaundice and dark urine are typical.

Inherited hemoglobin disorders

• Sickle cell disease: abnormal hemoglobin makes red cells sickle-shaped, causing chronic anemia, pain crises and organ damage.
• Thalassemia: reduced production of hemoglobin chains, ranging from mild trait to transfusion-dependent disease.

Aplastic anemia and marrow disorders

Aplastic anemia is failure of the bone marrow to make all blood cells, causing anemia, infections and bleeding. Leukemia, myelodysplastic syndrome and myeloma can also crowd out normal red cell production.

Risk factors

• Heavy menstrual periods
• Pregnancy, especially closely spaced pregnancies
• Infancy and adolescence growth spurts
• Vegan or vegetarian diets without supplements
• Age over 65
• Chronic kidney disease, heart failure, inflammatory diseases and cancer
• Regular use of NSAIDs or aspirin
• Gut conditions such as celiac disease, Crohn's disease, or previous stomach or bariatric surgery
• Family history of inherited anemias

Diagnosis

1. Complete blood count (CBC): confirms anemia and measures red cell size (MCV). White cells and platelets show whether the whole marrow is affected.
2. Reticulocyte count: high in bleeding and hemolysis, low in production problems.
3. Iron studies: a ferritin below about 30 ng/mL indicates iron deficiency in most adults. Inflammation raises ferritin, so it is interpreted with transferrin saturation and CRP.
4. Vitamin B12 and folate levels, with intrinsic factor antibodies if pernicious anemia is suspected.
5. Kidney, liver and thyroid function.
6. Blood film: a specialist looks at cell shapes under the microscope.
7. Hemolysis tests: bilirubin, LDH, haptoglobin and a direct antiglobulin (Coombs) test.
8. Hemoglobin electrophoresis for sickle cell disease and thalassemia.
9. Finding the source of iron loss: celiac screening, and upper endoscopy and colonoscopy for unexplained iron deficiency in men and in women after menopause.
10. Bone marrow biopsy if marrow failure or a blood cancer is suspected.

Treatment

Iron deficiency

• Oral iron: usually one tablet daily or every other day, which improves absorption and reduces side effects. Hemoglobin should rise about 1 to 2 g/dL within 4 weeks. Continue for about 3 months after it normalizes to refill stores.
• Side effects: constipation, nausea and dark stools. Taking iron with vitamin C or a small amount of food helps tolerance. Avoid taking it with tea, coffee, milk or antacids.
• Intravenous iron: for people who cannot tolerate or absorb tablets, have ongoing losses, CKD or inflammatory bowel disease, or need rapid correction late in pregnancy.
• Treat the source: manage heavy periods, stop NSAIDs where possible, treat ulcers and remove polyps or tumors.

B12 and folate deficiency

B12 is given by injection or high-dose tablets. Pernicious anemia needs lifelong treatment. Folic acid tablets correct folate deficiency, but B12 deficiency must be ruled out first, because folate alone can worsen nerve damage.

Anemia of chronic disease and CKD

Treating the underlying disease helps most. In CKD, IV or oral iron is given first, then ESAs if hemoglobin stays low, with targets that avoid raising it too high because that increases stroke and heart risks.

Hemolytic and inherited anemias

Treatments include steroids and other immune treatments for autoimmune hemolysis, stopping trigger medicines, folic acid supplements, hydroxyurea and newer therapies for sickle cell disease, and regular transfusions with iron chelation for severe thalassemia.

Blood transfusion

Transfusion is used for severe or symptomatic anemia, active bleeding, or when a rapid rise is needed. Most guidelines use a threshold of about 7 g/dL in stable patients, or 8 g/dL with heart disease.

Diet

Iron-rich foods include red meat, poultry, fish, beans, lentils, tofu, dark leafy greens and fortified cereals. Iron from meat (heme iron) is absorbed best. Pairing plant iron with vitamin C improves absorption. Diet alone rarely corrects established iron deficiency anemia, but it helps prevent recurrence.

Complications

• Heart strain, worsening angina and heart failure in severe or long-standing anemia
• Pregnancy complications: preterm birth and low birth weight
• Delayed growth and development in children
• Falls, confusion and reduced independence in older adults
• Nerve damage in untreated B12 deficiency
• Iron overload from repeated transfusions

Outlook

Most nutritional anemias resolve fully with treatment within 2 to 3 months, provided the underlying cause, such as bleeding, is addressed. Anemia from chronic disease improves as the disease is controlled. Inherited and marrow-related anemias need long-term specialist care, but treatments have improved significantly.

Prevention

• Iron-rich foods, and iron supplements in pregnancy if advised
• B12 supplements for vegans and people over 50 with poor absorption
• Folic acid before conception and in early pregnancy
• Seeing a doctor about heavy periods
• Regular blood counts if you have CKD, inflammatory disease or take medicines that affect the blood

Frequently asked questions

What is anemia?

Anemia is a condition in which you have fewer red blood cells or less hemoglobin than normal, so your blood carries less oxygen. It causes tiredness, weakness, pale skin and breathlessness. It has many causes, the most common being iron deficiency.

What are the main types of anemia?

The main types are iron deficiency anemia, vitamin B12 and folate deficiency anemia, anemia of chronic disease, anemia of chronic kidney disease, hemolytic anemia, inherited anemias such as sickle cell disease and thalassemia, and aplastic anemia.

What is the most common cause of anemia?

Iron deficiency is the most common cause worldwide. It usually results from blood loss, such as heavy periods or bleeding from the gut, from increased needs in pregnancy, or from low iron intake or poor absorption.

How long does it take to recover from anemia?

With iron tablets, hemoglobin usually rises within 2 to 4 weeks and returns to normal within about 2 to 3 months, and energy improves along the way. Iron stores take several more months to refill. B12 injections can improve symptoms within days to weeks.

Can anemia be cured?

Most anemias caused by iron, B12 or folate deficiency can be cured by correcting the deficiency and treating its cause. Anemia related to chronic kidney disease or inherited conditions is usually managed long term rather than cured.

What foods help with anemia?

Red meat, poultry, fish, beans, lentils, tofu, dark leafy greens and fortified cereals provide iron. Eggs, dairy, meat and fortified foods supply B12. Leafy greens, legumes and citrus fruit supply folate. Vitamin C-rich foods improve iron absorption from plant sources.