Anemia

Anemia is characterized by a reduction in either the hematocrit (red blood cell [RBC] volume <42% in men and <36% in women) or the concentration of hemoglobin (<14 g/dL in men and <12 g/dL in women). The prevalence of anemia is highest among menstruating women (5.8%), infants (5.7%), and the elderly (12%). Anemias can be distinguished morphologically based on the size of the RBCs or the mean corpuscular volume.

• Microcytic anemias are characterized by small RBCs (mean corpuscular volume <80 fL) and include iron-deficiency anemia, anemia of chronic disease, thalassemias, and sideroblastic anemias.
• Macrocytic anemias are characterized by large RBCs (mean corpuscular volume >98 fL) and include megaloblastic anemias (e.g., from vitamin B12 [pernicious anemia] and folic acid deficiencies), myelodysplastic anemias (e.g., from cancer chemotherapy), and liver disease (e.g., alcoholism).
• Normocytic anemias are characterized by RBCs within the normal size range (mean corpuscular volume, 80 to 98 fL) and include anemias of acute blood loss, acquired and inherited hemolytic anemias (e.g., sickle-cell anemia), mixed micro-macrocytic anemias, and anemias related to renal failure and bone marrow disease.

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Etiology

Anemia is caused by decreased production of RBCs resulting from deficiencies in the elemental ingredients necessary for RBC production, by increased destruction of RBCs (hemolysis) from defects in the RBC or environmental stressors, and from excessive bleeding.

Decreased production of RBC is caused by the following.

• Menstruation (monthly iron losses, 20 to 30 mg/month)
• Pregnancy (iron losses from increased needs and losses at the time of delivery) and lactation
• Iron, folic acid, vitamin B12, or erythropoietin deficiencies
• Chronic disease states (e.g., rheumatoid arthritis, inflammatory bowel disease, renal failure)
• Inherited anomalies (e.g., thalassemias)
• Gastrointestinal blood loss (e.g., ulcers, cancer, parasites)
• Genitourinary blood loss (e.g., pregnancy, uterine bleeding, menstruation)
• Overt blood loss (e.g., after surgery, chronic ingestion of nonsteroidal anti-inflammatory drugs [NSAIDs], or regular blood donations)
• Malabsorption syndromes (e.g., celiac disease)
• Neoplasia
• Alcohol ingestion

Increased destruction of RBC is caused by the following.

• Inherited anomalies (e.g., membrane, enzyme, or hemoglobin anomalies)
• Environmental stresses (e.g., antibody deposition, parasitic infection)
• Oxidant drugs (e.g., antibiotics, antimalarials, analgesics)—specific to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency

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Risk Factors

• Family history of anemia
• African-American with G6PD deficiency
• Mediterranean ancestry (thalassemia)
• Women in the reproductive years
• Inflammatory disease or advanced malignancy
• Drugs that injure the gastric or intestinal mucosa
• Parasitic infestation (e.g., malaria and babesiosis)
• Malnutrition
• Alcoholism
• Low-income elderly with poor diets

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Signs and Symptoms

There is tremendous variability among individuals in the clinical manifestations of anemia, which depend on the cause, severity, onset, and any underlying disease process. Generally symptoms occur when there is an acute drop in hemoglobin to 7 to 8 g/dL. However, if anemia develops slowly, patients may be able to tolerate hemoglobin levels as low as 6 to 7 g/dL before becoming symptomatic.

• Fatigue
• Headache
• Dyspnea (shortness of breath)
• Lightheadedness
• Pain in the abdomen and back
• Palpitations and angina
• Episodic jaundice and dark urine (i.e., hemoglobinuria)—specific to sideroblastic anemia
• Pica (cravings for strange foods) and koilonychia (thin, concave nails)—specific to iron-deficiency anemia
• Glossitis, jaundice, loss of vibratory and position sense, and neurologic symptoms, which may be permanent—specific to pernicious anemia (i.e., vitamin B12 deficiency)

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Differential Diagnosis

Many disorders, including congestive heart failure and hypersplenism.

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Diagnosis Physical Examination

Because anemia is often the result of an underlying disease process, the history and physical examination are extremely important. Anemic patients are often pale and may appear confused, frail, unsteady, and short of breath. The presenting symptom may be chest pain or syncope. Vital sign abnormalities include hypotension or tachycardia. Anemia is defined by the laboratory values and these values and the clinical picture are necessary for a definitive diagnosis.

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Laboratory Tests

• Complete blood count (CBC)
• Peripheral blood smear
• Reticulocyte count
• Stool for occult blood
• Serum iron studies
• Platelet count
• Blood test for B12 and folic acid

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Pathology/Pathophysiology

• Low, normal, or high mean corpuscular volume defines microcytosis, normocytosis, or macrocytosis, respectively.
• Poilkilocytosis (abnormal variation in shape of RBCs) as described by the red cell distribution width
• Hypochromia (decreased hemoglobin content of RBCs)
• Reticulocytosis (increased number of reticulocytes [immature RBCs]) is an important distinguishing characteristic of hemolytic anemia.
• A decreased number of reticulocytes is an important distinguishing characteristic of hypoproliferative anemia.
• Iron accumulation is specific to sideroblastic anemia.
• Low serum iron is specific to iron deficiency anemia.
• Pancytopenia.
• Sickled RBCs are specific to sickle-cell anemia.
• Elevated blood urea nitrogen and serum creatinine are specific to anemia of chronic renal failure.

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Imaging

May need abdominal sonogram to check spleen size.

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Other Diagnostic Procedures

• Coulter counter (for CBC)
• Radioimmunoassay (to measure vitamin B12 levels)
• Bone marrow examination
• Gene mapping for alpha and beta chains (for thalassemias) and for sickle-cell disease
• Schilling test
• Coombs antiglobulin test
• Hemoglobin electrophoresis
• Erythrocyte sedimentation rate
• Creatinine levels
• Liver function tests
• Thyroid profile
• GI exam for source of bleeding

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Treatment Options Treatment Strategy

Therapy for anemia depends on the cause and the severity of the anemia. In some anemias, the therapy is well established; in others the therapy is largely expectant, depending on the successful treatment of the underlying disease (e.g., anemia of chronic disease). Avoid oxidant medications in patients with G6PD deficiency.

Other treatment options include the following.

• Supportive care (e.g., transfusions), folic acid, and fluids—for patients with sickle cell anemia
• Supportive care (e.g., transfusions), symptomatic therapy, bone marrow transplantation, and splenectomy—for the alpha and beta thalassemias
• Splenectomy—for hereditary spherocytosis

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Drug Therapies

• Erythropoietin plus iron—for anemia of chronic renal failure
• Steroids (e.g., prednisone), splenectomy, cytotoxic agents (e.g., azathioprine), or transfusions—for autoimmune hemolytic anemia
• Analgesics (for painful crises)—for sickle-cell anemia
• Cessation of offending drugs—for acquired forms of sideroblastic anemia
• Iron replacement
• Transfusions
• Treatment of underlying disorders

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Complementary and Alternative Therapies

Most cases of macrocytic and microcytic anemias may respond well to nutritional therapy. Patients need to be counseled that excess iron is toxic and should not be taken unless indicated by abnormal lab values. Herbal and dietary treatments may be helpful as adjunctive.

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Nutrition

• Ferrous fumerate, glycerate or glycinate (100 mg/day for three to six months) are the most absorbable forms of iron. Ferrous sulfate (325 mg/day) is poorly absorbed and more frequently causes problems with GI upset and/or constipation. Dietary sources of iron include meat, beans, green leafy vegetables, beet greens, blackstrap molasses, almonds, and brewer's yeast.
• Vitamin C—for pernicious anemia, up to 1,000 mg tid will aid in absorption of iron.
• Vitamin B12—cyanocobalamine, 1,000 IU intramuscular injection bid for one week, then weekly for one month, then every two to three months. (Note that dosing varies depending on individual case.) Dietary sources include organ meats, meats, eggs, fish, and cheese.
• Folic acid (1 to 2 mg/day)—for folic acid deficiency and hereditary spherocytosis. Good food sources include green leafy vegetables and grains.
• Omega-3 and omega-6 essential fatty acids (1,000 to 1,500 IU) have been shown to decrease the frequency of sickle-cell crisis. EFAs can increase clotting times so may need to be checked in people on anticoagulants.

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Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, it is important to ascertain a diagnosis before pursuing treatment. Herbs may be used as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, teas should be made with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Drink 2 to 4 cups/day. Tinctures may be used singly or in combination as noted.

Patients may be treated for one to three months and then reassessed.

• Blackstrap molasses, also known as pregnancy tea (1 tbsp./day in a cup of hot water), is a good source of iron, B vitamins, minerals, and is also a very gentle laxative.
• Spirulina, or blue-green algae, has been used successfully to treat both microcytic and macrocytic anemias. Dose is 1 heaping tsp./day.
• Alfalfa (Medicago sativa), dandelion (Taraxacum officinale) root or leaf, burdock (Arctium lappa), and yellowdock (Rumex crispus) have long been used to fortify and cleanse the blood. For mild cases of anemia, they may help to bring lab values into normal range. Dosage is 1 tbsp./cup of water. Simmer roots for 20 minutes and leaves for 5 minutes. A single herb, or a combination of these four herbs, may be used.

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Homeopathy

An experienced homeopath should assess individual constitutional types and severity of disease to select the correct remedy and potency. Use Ferrum phosphoricum 12C once a day for iron deficiency anemia.

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Patient Monitoring

The frequency of checking the CBC for anemia depends on its cause and severity. Patients should be counseled to maintain a normal balanced diet containing all of the nutrients necessary for blood formation and on the potential adverse gastric effects of certain drugs. Vegetarians need to pay close attention to sources of vitamin B12 and iron, and may need to take supplements.

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Other Considerations Prevention

It can take three to five years to develop a vitamin B12 deficiency. Folic acid is more rapidly depleted, and deficiency can manifest within a few months. B12 requires sufficient hydrochloric acid for proper utilization. Macrocytic anemia treated with only folate may mask a B12 deficiency—leading to rare cases of permanent nerve damage. Therefore, B12 should be given with folate.

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Complications/Sequelae

Complications for anemia can range from loss of productivity due to weakness and fatigue to myocardial infarction and death.

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Prognosis

The expected course and prognosis is dependent on the type of anemia and the treatment.

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Pregnancy

Pregnant women need three to four times as much iron as normal (10 mg/day); thus, the increased demands of pregnancy and blood loss at the time of delivery can lead to iron-deficiency anemia (iron, B12, and/or folate). Iron-deficiency anemia can result in premature labor, post-partum hemorrhage, low-birth-weight infants, perinatal mortality and can contribute to post-partum depression. A folic acid deficiency during pregnancy, but most importantly in the three months prior to conception, increases the risk of neural tube defects in the infant.

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References

Branch WT Jr. Office Practice of Medicine. Philadelphia, Pa: WB Saunders Company; 1994.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998.

Kelley WN, ed. Textbook of Internal Medicine. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1997.

Tyler VE. The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. 3rd ed. Binghamton, NY: Pharmaceutical Products Press; 1993.

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