AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Anemia is defined as an absolute reduction in the quantity of the oxygen-carrying pigment hemoglobin (Hgb) in the circulating blood. Anemia is further broadly subcategorized into acute and chronic. Viewing anemia as a symptom of a disease manifested by low Hgb rather than as an isolated diagnosis is often helpful.

Pathophysiology

Anemia usually is grouped into 3 etiologic categories: decreased red blood cell (RBC) production, increased RBC destruction, and blood loss.

A disease may lead to anemia through a combination of several mechanisms. For example, a GI malignancy may manifest blood loss as well as anemia of chronic disease.

Frequency

United States

Incidence of anemia mirrors the incidence of the underlying cause. Some published studies report the incidence of anemia at 2-15% in the United States and Great Britain.

International

Anemia is far more common in underdeveloped countries than in the United States. The true incidence of anemia is difficult to define because of multiple factors (eg, patient population, geographic location, normal range reference, ability to adequately screen for the disease).

Mortality/Morbidity

Morbidity and mortality are dependent on several variables (eg, underlying disease process, comorbid conditions, chronicity of the disease, patient's diet, patient's access to medical care).

Race

• African Americans have a higher incidence of sickle cell anemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. G-6-PD is essential for RBC protection from oxidative insults and for approximately 10% of RBC energy production.
• Mediterranean populations show a higher incidence of beta thalassemia.

Sex

Sex distribution varies based on the underlying cause. Overall, females have approximately twice the incidence of males of anemia.

Age

Anemia is prevalent in all age groups. Some younger patients may have a better ability to compensate for anemia, which may delay initial diagnosis.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

A comprehensive history and physical examination is vital in determining the cause of anemia. For example, a family history of a dominant inheritance pattern would suggest spherocytosis. In addition, knowing what medications the patient is taking is vital, as many drugs and toxins can cause anemia (eg, alcohol, isoniazid, lead). The spectrum of symptoms manifested by anemia is dependent on many factors, including underlying medical condition, medications, rate of onset, and the individual's ability to compensate for the deficit. The hallmark of chronic anemia is the ability of patients to sustain a relatively normal level of function at significantly lower than normal Hgb levels.

• Primary symptoms result from tissue hypoxia and might include the following:
• • Fatigue, weakness, irritability
  • Headache
  • Dizziness, especially postural
  • Vertigo
  • Tinnitus
  • Syncope
  • Dyspnea, especially with increased physical activity (exercise intolerance)
  • Chest pain, palpitations
  • Difficulty sleeping or concentrating
  • Thirst
  • Anorexia
  • Decreased urine output/bowel irregularity
  • Decreased libido or impotence
• Anemia is a manifestation of an underlying disease process and is not a diagnosis in itself. A wide array of diseases, including inflammations, infections, and malignancies, may at some point be associated with anemia. Common conditions associated with anemia include the following:
• • Gastritis
  • Gastric or duodenal ulcer
  • Liver or renal disease
  • Hypothyroidism
  • Sickle cell disease
  • Hypermenorrhea
  • Previous history of anemia or blood transfusions
  • Thrombocytopenia or blood coagulation disorders
  • Cancer or other chronic illness (eg, rheumatic disease)
  • Poor diet, especially iron deficiency

Physical

Physical findings mirror the underlying disease process and the duration from the onset. Patients with chronic anemia usually do not manifest typical physical findings associated with acute anemia. Potential physical findings include the following:

• Skin pallor
• • The usefulness of this sign is limited by the color of the skin, Hgb concentration, and the fluctuation of blood flow to the skin.
  • The color of the palmar creases is a better indicator. If they are as pale as the surrounding skin, Hgb is usually less than 7 g/dL. Patients also may exhibit purpura, petechiae, and jaundice.
• Eyes
• • Pale conjunctiva
  • Retinal hemorrhages
• Cardiovascular
• • Tachycardia
  • Orthostatic hypotension
• Pulmonary
• • Tachypnea
  • Rales
• Abdomen
• • Hepatomegaly and/or splenomegaly
  • Ascites
  • Masses
  • Positive result on Hemoccult test
• Neurologic
• • Peripheral neuritis/neuropathy
  • Mental status changes

Causes

The first question a clinician must address is whether the anemia is due to a decreased production of RBCs or to increased destruction or loss of RBCs. The reticulocyte count is the most valuable test in answering this question. If the reticulocyte count is low, a failure in RBC production is indicated. If it is high, hemolysis is suggested.

• Hypochromic microcytic anemia
• • Possible causes include iron deficiency, thalassemia, sideroblasts, and lead poisoning.
  • Anemia of chronic disease commonly is manifested by normocytic normochromic indices; however, microcytic hypochromic indices also can be associated with anemia of chronic disease.
• Macrocytic anemia: Possible causes include vitamin B-12 deficiency, folate deficiency, liver disease, and hypothyroidism.
• Normocytic anemia is further divided into 2 broad categories.
• • Primary bone marrow involvement
  • • Aplastic anemia
    • Myelophthisic anemia: Pathogenesis involves interruption of normal hematopoiesis due to the accumulation of malignant or reactive cells or cell products. It is characterized by the appearance of immature myeloid cells and nucleated RBCs in the peripheral blood. The 3 major classes of disorders that can produce myelophthisic anemia are intrinsic bone marrow malignancies (eg, leukemia, lymphoma, myeloma), metastatic tumors (eg, neuroblastoma, melanoma, cancers that are more prone to bone marrow metastasis (eg, prostate, breast, lung, stomach, renal carcinomas), and granulomatous disease (eg, tuberculosis, sarcoidosis).
    • Myeloid metaplasia is known as agnogenic myeloid metaplasia and involves gradual bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly with no known underlying systemic disorder.
  • Anemia secondary to underlying disease: Most cases of anemia in the world are secondary to an underlying disease. The marrow does not respond appropriately to microcytic anemia, leading to decreased production of RBC. This type of anemia includes liver cirrhosis, uremia, chronic inflammation, and hypoendocrine conditions (eg, thyroid, adrenal, pituitary disorders).
• Hemolytic anemias: This type of anemia includes sickle cell anemia, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, aortic valve prosthesis, disseminated intravascular coagulation (DIC), cold agglutinin disease, and paroxysmal cold hemoglobinuria (PCH).

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• The 3 laboratory measurements that are critical in the workup of anemia are as follows:
  • Measurement of RBC indices
  • Examination of peripheral blood smear
  • Bone marrow examination (not necessary in all patients)
• Additional laboratory tests that allow differentiation of anemias based on RBC index information include the following:
  • Serum iron concentration
  • Total iron-binding capacity (TIBC)
  • Serum vitamin B-12
  • Serum folate
  • Serum bilirubin
  • LFTs
  • Thyroid panel
  • Hgb electrolytes
  • Heavy metal studies
• The ultimate diagnosis of chronic anemia is based on results of blood studies. In the initial emergency department (ED) evaluation, a prudent choice of labs includes the following:
• • Complete blood count (CBC) with leukocyte differential and peripheral smear
  • Red blood cell indices
  • Reticulocyte count
  • Bilirubin
• Based on the RBC indices, further blood work may be initiated in the ED, including the following:
• • Iron studies may be performed. These can include ferritin, TIBC, total iron, and percent saturation. Typically, iron studies are helpful in the diagnosis of microcytic and normocytic anemias.
  • Serum vitamin B-12, folate levels, and the red cell folate level are useful in evaluating macrocytic anemias. Order concurrent liver and thyroid function studies for patients with macrocytic anemia.
  • Hgb electrophoresis may delineate sickle cell anemia and thalassemias.
  • Heavy metal studies (eg, serum lead level) may be considered when a high level of suspicion is present, both historically and clinically, for heavy metal poisoning.
• The significance of common lab studies ordered in the ED in evaluation of anemia is as follows:
• • Hematocrit also is known as the packed cell volume (PCV) and indicates the percentage of RBCs in a volume of whole blood. Increased values occur with severe dehydration, erythrocytosis, polycythemia, severe burns, shock, and in people living in high altitudes, males, and infants. Decreased values occur with anemia and the many differential diagnoses that encompass anemia (eg, hyperthyroidism, leukemia, liver disease, hemolytic reactions). Other causes of decreased hematocrit values include female sex, advanced age, and pregnancy. Hematocrit value is not reliable immediately after blood loss or blood transfusions.
  • Hgb concentration is expressed in grams per 100 mL of blood. Increased values can indicate severe dehydration, erythrocytosis, polycythemia, severe burns, shock, chronic obstructive pulmonary disease (COPD), or congestive heart failure (CHF). Increased values also occur in people living in high altitudes, people consuming drugs such as gentamicin or methyldopa, and infants. Decreased values indicate anemia and the many differential diagnoses that encompass anemia (eg, hyperthyroidism, leukemia, liver disease, hemolytic reactions). Other possible causes of decreased Hgb values include overhydration, pregnancy, and drugs (eg, acetaminophen, antineoplastic agents, chloramphenicol, hydralazine, monamine oxidase inhibitors [MAOIs], nitrites, penicillin, tetracycline, sulfonamide). Each gram of Hgb has a carrying capacity of 1.34 mL of oxygen.
  • Mean corpuscular volume (MCV) is the hematocrit divided by the RBC count. It is a measurement of the volume occupied by a single RBC and is an indicator of individual cell size. Increased values indicate differentials that encompass macrocytic anemia (eg, vitamin B-12 or folate deficiency, liver disease, alcoholism), while decreased values indicate microcytic anemia (ie, iron deficiency, thalassemia, anemia of chronic blood loss). This is the most important of the RBC indices. A normal value can appear when a wide variety of cell sizes is present (ie, macrocyte, microcyte).
  • Mean corpuscular Hgb concentration (MCHC) is the Hgb divided by the hematocrit. It represents average concentration of Hgb in the red blood cells. The value is expressed as a percentage. Increased values point to spherocytosis (eg, congenital hemolytic anemia), and decreased values indicate iron deficiency, thalassemia, or macrocytic anemia.
  • Mean corpuscular Hgb (MCH) is the Hgb divided by the RBC count. It represents the average weight of Hgb in the RBCs and serves to confirm the accuracy of MCV value. Increased values occur in macrocytic anemia, newborns, and infants. Decreased values indicate microcytic anemia.
  • Reticulocyte count: A reticulocyte is a nonnucleated, immature RBC formed in the bone marrow. Increased values indicate accelerated erythropoiesis and can be present following treatment of anemia, after splenectomy 3-4 days following hemorrhage, in sickle cell disease hemolytic anemia, during pregnancy, or in infants. Decreased values indicate decreased RBC production by the bone marrow and can be a result of aplastic anemia, chronic infection, or radiation therapy. A persistent reticulocyte deficiency is a poor prognostic sign.
  • Reticulocyte index (RI): The RI is defined as the percent reticulocyte count divided by 2 and then multiplied by the ratio of the patient's hematocrit (or Hgb) to normal hematocrit (or Hgb). Good marrow response is defined as an RI value of 2-6.

Imaging Studies

• No specific imaging tests exist for chronic anemia; however, several imaging modalities are helpful based on the underlying etiology (eg, CT scanning for abdominal mass, chest radiography for histoplasmosis/coccidioidomycosis).

Other Tests

• Bone marrow examination may be diagnostic in cases in which workup is otherwise nonspecific. This is not a procedure performed in the acute setting.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Prehospital care most often is initiated for patients in extremis. Attention to ABCs is most appropriate. All such patients should have IV placement, fluid resuscitation, and airway management as necessary.
• Initial status and appearance of the patient may hold useful information and should be elicited from prehospital personnel.
• Most patients presenting with chronic anemia are not in distress.

Emergency Department Care

• Patients with chronic anemia usually do not require intervention in the ED. Ultimate treatment requires investigation into the etiology of the anemia and correction of the underlying cause.
• Records of previous hospitalization or ED visits are invaluable in many aspects. Such patients frequently have undergone previous workup, and trends of previous Hgb or hematocrit indicate the time course of the illness.
• EDs rarely treat anemia beyond the emergent needs. Discharging the patient on iron, vitamin B-12, or folate may mask other problems and cloud the correct diagnosis.
• Transfusions
• • One conspicuous exception in the treatment of chronic anemia is the use of transfusion therapy. Unless cardiopulmonary or cerebrovascular disease is present, transfusion is rarely needed in patients who have chronic anemia with an Hgb greater than 7 g/dL. Multiple situations that may require transfusion include angina, CHF, transient ischemic attack (TIA), and signs of tissue hypoxia.
  • It is important to weigh the risks and benefits of blood transfusion.
  • Many adverse reactions are associated with transfusion therapy. Most frequently encountered is a febrile nonhemolytic reaction. Patients who have had previous transfusion or patients who are pregnant are at greatest risk. Treatment is supportive with antipyretics. The clinician should maintain a high level of suspicion for a hemolytic reaction because fever may the first symptom.
  • Many patients fear infection. Hepatitis C occurs in 1 of 103,000 transfusions, hepatitis B occurs in 1 of 200,000 transfusions, and human immunodeficiency virus (HIV) occurs in 1 of 490,000 transfusions.
  • The graft versus host reaction is rare but is especially dangerous in patients who are immunocompromised. It carries a mortality rate higher than 90%. Pathogenesis in this reaction involves donor T lymphocytes attacking host human leukocyte antigens (HLA). High fever, erythematous rash, diarrhea, and abnormal LFTs associated with recent or concurrent transfusion may herald the severe reaction. Symptoms may not appear until 8 days after transfusion, and death occurs in 3-4 weeks. Using irradiated blood can decrease the incidence of graft versus host reaction and should be considered in all patients deemed immunocompromised, as well as in fetuses receiving intrauterine transfusions, patients receiving units from a blood relative, and patients transplanted with marrow. Care should be taken when transfusing patients with CHF. Preferably, transfusion should occur over 3-4 hours in the sitting position.

Consultations

• Generally, patients with chronic anemia can be treated on an outpatient basis, and referral to a primary care provider is appropriate.
• Consultation with the patient's primary care provider or an available internist should begin in the ED.
• Symptomatic patients with an underlying medical condition that requires surgical consultation, such as chronic GI bleeding from colon cancer, should be evaluated by a surgeon in the ED.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with chronic anemia requiring admission include the following:
• • Patients presenting with hypovolemia, active bleeding, angina, tachypnea, altered mental status, TIA, or exacerbation of CHF
  • Patients who demonstrate a considerable drop in Hgb and hematocrit values when compared to previous values or have new-onset or worsening pancytopenia
  • Patients with an initial Hgb less than 10 g/dL or hematocrit less than 30%
  • Patients who may not comply with follow-up or those in whom the clinician anticipates the need for an extensive workup
• Patients can be admitted to a ward bed, a monitored bed, or an ICU bed, depending on their condition.

Further Outpatient Care

• Patients with chronic anemia most often are treated in the outpatient setting. Clear instructions must be given to the patient regarding proper follow-up.
• Considering the financial situation and outpatient capability to comply with follow-up of these patients is imperative. The key to minimizing complications from chronic anemia is ongoing reassessment and compliance with proposed medical therapy.
• All efforts should be made to arrange for follow-up. When all avenues for outpatient evaluation fail, patients should be instructed to return to the ED for reassessment in 2-3 weeks.
• Upon discharge, instruct the patient to watch for signs and symptoms of worsening anemia. The patient should be advised to return to the ED if such symptoms develop.

Transfer

• Patients with chronic anemia seldom require transfer to another facility for definitive care. Transfers are only acceptable if the patient is hemodynamically stable.

Complications

• Failure to comply with follow-up and treatment regimens predisposes patients with chronic anemia to complications.
• The majority of complications arise from chronic or persistent tissue hypoxia.
• Pediatric patients, elderly patients, and patients who are immunocompromised are at the highest risk for complications, since they have less physiological reserve.

Prognosis

• Prognosis is dependent on several factors. The underlying medical condition usually dictates the prognosis, but comorbid conditions, the patient's age, and the patient's access to medical care are contributing factors.

Patient Education

• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Anemia.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to identify acute blood loss while attributing low Hgb and hematocrit values to a chronic state
• Failure to recognize anemia as an etiologic factor for patients who present with dyspnea, headache, angina, or altered mental status
• Failure to recognize anemia as the contributing factor to jaundice (hemolytic anemia) while focusing on other conditions, such as acute hepatitis, that can present with jaundice
• Failure to recognize the presence of pancytopenia while focusing mainly on anemia
• Failure to provide appropriate instructions for return

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Binder LS. Anemia. In: Harwood-Nuss AL, Linen CH, eds. The Clinical Practice of Emergency Medicine. Philadelphia, Pa: Williams & Wilkins; 1996:915-7.
• Chandrasoma P, Taylor CR. The blood and lymphoid system. In: Concise Pathology. New York, NY: McGraw-Hill; 1991:374-406.
• Dzieczkowski JS, Anderson KC. Transfusion biology and therapy. In: Harrison TR, ed. Harrison's Principles of Internal Medicine. Vol 1. New York, NY: McGraw-Hill; 1998:718-24.
• Fischbach FT. Blood studies. In: A Manual of Laboratory Diagnostic Tests. Philadelphia, Pa: Williams & Wilkins; 1984:25-8, 867-8.
• Hamilton GC. Anemia, polycythemia, and white blood cell disorders. In: Rosen P, Barkin RM, eds. Emergency Medicine Concepts and Clinical Practice. Vol 3. 4^th ed. St. Louis: Mosby; 1998:2053-2076.
• Lux SE, Fruchtman SM, Berk PD. Introduction to anemias: Polycythemia vera and agnogenic myeloid metaplasia. In: Handin RI, Lux SE, Stossel TD, eds. Blood: Principles and Practice of Hematology. Philadelphia, Pa: Williams & Wilkins; 1995:430-5, 1391-2.
• Rapaport SI. Diagnosis of anemia. In: Introduction to Hematology. Philadelphia, Pa: Williams & Wilkins; 1987:10-38.
• Rhule RL. Anemia. In: Schwarz GR, ed. Principles and Practice of Emergency Medicine. Vol 2. Philadelphia, Pa: Williams & Wilkins; 1992:1966-77.
• Tarasiuk A, Abdul-Hai A, Moser A, et al. Sleep disruption and objective sleepiness in children with beta-thalassemia and congenital dyserythropoietic anemia. Arch Pediatr Adolesc Med. May 2003;157(5):463-8. [Medline].
• Williams MD, Wheby MS. Anemia in pregnancy. Med Clin North Am. May 1992;76(3):631-47. [Medline].

Article Last Updated: Jan 14, 2008