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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e

Chapter 231: Chapter 231: AnemiaAnemia John C. Ray; Robin R. Hemphill

INTRODUCTIONINTRODUCTION

Anemia is a common medical problem worldwide, a�ecting approximately one quarter of the world'spopulation, especially children, pregnant and premenopausal women, the elderly, and the chronically

ill.1,2,3,4,5,6,7 Anemia is not so much a disease as a sign or symptom. There are three broad causes of anemia:(1) blood loss, (2) decreased red blood cell production, and (3) increased red blood cell destruction.

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Anemia is a reduced concentration of red blood cells (RBCs) from the normal ranges based on age, gender,

and race.8 In healthy persons, normal erythropoiesis ensures that the concentration of RBCs present isadequate to meet the body's demand for oxygen and that the destruction of RBCs balances the production.The average life of the circulating erythrocyte is approximately 110 to 120 days. Any process or condition thatresults in the loss of RBCs, that impairs RBC production, or that increases RBC destruction will result inanemia if the body cannot produce enough new cells to replace those lost (Table 231-1Table 231-1). It is not uncommonfor more than one mechanism to produce anemia in the same individual.

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TABLE 231-1

Classification of AnemiaClassification of Anemia

MechanismMechanism ExampleExample

Loss of red blood cells by hemorrhage Acute GI bleeding

Increased destruction Sickle cell disease

Drug-induced autoimmune hemolytic anemia

Impaired production Nutritional deficiency anemia (iron, folate)

Aplastic or myelodysplastic anemia

Dilutional Rapid IV crystalloid infusion

Quantification of the erythrocyte concentration is reflected in (1) RBC count per microliter, (2) hemoglobinconcentration, and (3) hematocrit (percentage of RBC mass to blood volume). Normal RBC values for adultsvary between genders, with small variations for ethnicity and age (Table 231-2Table 231-2).

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Note: Normal values may vary depending on the equipment used, patient's age, and the altitude of the equipment

location.

TABLE 231-2

Normal Red Blood Cell Values for AdultsNormal Red Blood Cell Values for Adults

MaleMale FemaleFemale

Red blood cell count (million/mm3) 4.5–6.0 4.0–5.5

Hemoglobin (grams/dL) 14–17 12–15

Hematocrit (%) 42–52 36–48

Mean corpuscular volume (fL) 78–100 78–102

Mean corpuscular hemoglobin (picograms/cell) 25–35 25–35

Mean corpuscular hemoglobin concentration (grams/dL) 32–36 32–36

Red cell distribution width (%) 11.5–14.5 11.5–14.5

Reticulocytes (%) 0.5–2.5 0.5–2.5

The body responds to anemia in several ways in order to blunt the e�ect of a reduction in the oxygen-carrying capacity. The mechanisms vary, depending on the rapidity of onset, the degree of anemia, and theunderlying condition of the patient. In acute forms of anemia that result from intravascular volume loss, theperipheral vasculature compensates by vasoconstriction, while the central vasculature vasodilates to help

preserve blood flow to vital organs.9 As the condition worsens, systemic small-vessel vasodilation will occur,allowing increased blood flow to tissues. These mechanisms result in decreased systemic vascularresistance, increased cardiac output, and o�en tachycardia. Along with these changes, the RBCs themselvesenhance their ability to release oxygen to the tissues. If the anemia is chronic in nature, there is commonly anincrease in plasma volume that maintains total blood volume at a constant level. Finally, anemia will result inthe stimulation of erythropoietin as a result of tissue hypoxia and breakdown products from RBCdestruction. New immature erythrocytes, known as reticulocytes, will appear in the blood within 3 to 7 days.

CLINICAL FEATURESCLINICAL FEATURES

The severity of signs and symptoms related to anemia depends on several factors: the rate of development ofanemia (acute vs chronic), the extent of anemia that is present, the age and general physical condition of the

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patient, and other existing comorbidities. Children and young adults, for example, may tolerate a significantdecline in RBC volume with minimally altered vital signs until they become acutely hypotensive, whereas

elderly patients frequently have other comorbidities that make physiologic compensation challenging.3,4

Patients with chronic and slowly developing anemia may have no complaints even with hemoglobin levels aslow as 5 to 6 grams/dL. Typically, most otherwise healthy adults will be symptomatic when hemoglobinlevels decrease to about 7 grams/dL.

Patients with chronic anemia may note weakness, fatigue, dizziness, lethargy, dyspnea with minimalexertion, palpitations, and orthostatic symptoms. Specific historical features can be helpful in theidentification and diagnosis of anemia; a history of recent trauma, hematochezia, melena, hemoptysis,hematemesis, hematuria, or menorrhagia suggests possible anemia. More subtle historical features includerelevant comorbidities such as peptic ulcer disease, chronic liver disease, and chronic renal disease. Specificinquiries about the use of antiplatelet agents, anticoagulants, and nonsteroidal anti-inflammatory agentsshould be made.

Physical exam findings that may be present in patients with clinically significant anemia include tachycardia;skin, nail bed, and mucosal pallor; systolic ejection murmur; bounding pulse; and widened pulse pressure(Figure 231-1Figure 231-1). Signs of easy bleeding or bruising suggest a coagulation disorder. Evidence of jaundice andhepatosplenomegaly suggests hemolysis. Unusual skin ulcerations, peripheral neuropathy, or neurologicsigns such as ataxia or altered mental status may be evidence of nutritional deficiencies. Additionalmanifestations may depend on comorbid illnesses. For example, a patient with preexisting angina may findthat episodes of chest pain are markedly worsened when anemia is present.

FIGURE 231-1.FIGURE 231-1.

Pale conjunctiva (AA) and palms (BB) in patient with anemia. In BB, the physician's hand is on the le� forcomparison with the patient's hand on the right. [Image used with permission of J. Stephan Stapczynski,MD.]

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Patients who develop an acute, severe anemia may have all the signs and symptoms noted above and, inaddition, may have hypotension, resting and exertional dyspnea, palpitations, diaphoresis, anxiety, or severeweakness that may progress to lethargy and altered mental status. They may also complain of thirst and willusually have decreased urine output. Loss of >40% of blood volume from trauma or spontaneoushemorrhage can lead to severe symptoms that are due more to intravascular volume depletion than to

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anemia.10 In healthy patients, myocardial oxygen delivery usually is not limited until hemoglobinconcentration is 50% or less of normal.

DIAGNOSISDIAGNOSIS

The diagnosis is established by a finding of decreased RBC count, hemoglobin, and hematocrit on the routineCBC. It is rarely essential that a specific cause of anemia be established in the ED. However, appropriateassessment initiated in the ED can help expedite a diagnosis and should therefore be started before the

transfusion of packed RBCs.6,8

The initial evaluation of a patient newly diagnosed with anemia includes several steps. First, look for a sourceof bleeding, including the most common internal sites—GI or uterine bleeding. If there is no physical orhistorical evidence of GI or uterine bleeding, then review RBC indices provided with the CBC, reticulocytecount, and peripheral blood smear (Table 231-3Table 231-3). The mean corpuscular volume is the most useful guide tothe possible etiology of an anemia and is used to classify the anemic process as microcytic, normocytic, ormacrocytic. Other useful diagnostic tests include the red cell distribution width and reticulocyte count. The

serum ferritin is the most useful test for the diagnosis of iron deficiency anemia.11 Following this initial

classification, additional tests can lead to a specific diagnosis (Figures 231-2Figures 231-2, , 231-3231-3, and 231-4231-4).5,7,8,12,13,14,15

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TABLE 231-3

Laboratory Tests in the Evaluation of AnemiaLaboratory Tests in the Evaluation of Anemia

TestTest InterpretationInterpretation Clinical CorrelationClinical Correlation

MCV Measure of the average RBC size. Decreased MCV (microcytosis) is seen in chronic

iron deficiency, thalassemia, anemia of chronic

disease, and lead poisoning.

Increased MCV (macrocytosis) can be due to vitamin

B12 or folate deficiency, alcohol abuse, liver disease,

reticulocytosis, and some medications (see

"Diagnosis" section).

MCH Measure of the amount of

hemoglobin in average RBC.

—

RDW Measures the size variability of the

RBC population.

In early deficiency anemia (iron, vitamin B12, or

folate), may be increased before the MCV becomes

abnormal.

MCHC Measure of hemoglobin

concentration in average RBC.

Low MCHC can be seen in iron deficiency anemia,

defects in porphyrin synthesis, and hemolytic

anemia.

Ferritin Ferritin is a protein in the body that

binds to iron. Serum levels serve as

an indication of the amount of iron

stored in the body.

Low serum ferritin is associated with iron deficiency

anemia and helps di�erentiate this anemia from

other causes.

Reticulocyte

count

These RBCs of intermediate maturity

are a marker of production by the

bone marrow.

Decreased reticulocyte count reflects impaired RBC

production.

Increased counts are a marker of accelerated RBC

production.

Peripheral

blood

smear

Allows visualization of the RBC

morphology.

May guide to new diagnosis of diseases such as

sickle cell disease.

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Abbreviations: MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV =

mean corpuscular volume; RBC = red blood cell; RDW = red cell distribution width.

TestTest InterpretationInterpretation Clinical CorrelationClinical Correlation

Allows evaluation for abnormal cell

shapes.

Aids in the diagnosis of entities such as hemolytic

anemia.

Allows examination of the WBCs and

platelets.

May guide the diagnosis of other diseases that

cause anemia.

Direct and

indirect

Coombs test

Direct Coombs test is used to detect

antibodies on RBCs.

Direct Coombs test is positive in autoimmune

hemolytic anemia, transfusion reactions, and some

drug-induced hemolytic anemia.

Indirect Coombs test is used to detect

antibodies in the sera.

Indirect Coombs test is routinely used in

compatibility testing before transfusion.

FIGURE 231-2.FIGURE 231-2.

Evaluation of macrocytic anemia. MCV = mean corpuscular volume; RDW = red cell distribution width.

FIGURE 231-3.FIGURE 231-3.

Evaluation of normocytic anemia. MCV = mean corpuscular volume; RDW = red cell distribution width.

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FIGURE 231-4.FIGURE 231-4.

Evaluation of microcytic anemia. MCV = mean corpuscular volume; RBC = red blood cell; RDW = red celldistribution width.

Macrocytosis can result from multiple causes; most common are alcohol abuse, liver disease, vitamin B12

and/or folate deficiency, and hypothyroidism.14,15 A variety of medications can a�ect folate absorption ormetabolism and produce macrocytosis. Drugs include phenytoin, valproate, trimethoprim,

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sulfamethoxazole, and metformin. The reverse transcriptase inhibitors used to treat humanimmunodeficiency virus infection can also produce macrocytosis, but they do so without causing anemia.Reticulocytes are larger than mature RBCs, so automated blood cell counters can report a mean corpuscularvolume value above the normal range when an increased reticulocyte count is present.

TREATMENTTREATMENT

The treatment of anemia depends on the etiology, symptoms, and clinical status of the patient. In the ED,

anemia that requires the most urgent attention results from acute blood loss.10 All patients who haveongoing blood loss and anemia should have their blood typed and cross-matched, so that information isavailable for transfusion, if needed (see chapter 238, "Transfusion Therapy"). The decision to transfuse RBCsmust be individualized for each patient, taking into account clinical symptoms, age of the patient, presence

of comorbid disease, and the likelihood of further blood loss.16,17,18,19,20 In general, patients who aresymptomatic and hemodynamically unstable and show evidence of tissue hypoxia and/or limitedcardiopulmonary reserve should have RBCs transfused. In most settings, patients with anemia resulting fromacute blood loss benefit when transfused at hemoglobin levels of 6 to 8 grams/dL. Liberal transfusionstrategy (defined as a hemoglobin threshold of 9.5 to 10 grams/dL) is not associated with clinical benefit, so ahemoglobin value threshold of 6 to 8 grams/dL for RBC transfusion is recommended in most

circumstances.21

ED patients with chronic anemia or a newly diagnosed anemia of uncertain etiology not caused by acuteblood loss may not require immediate transfusion unless they are hemodynamically unstable, hypoxic, orhave acidosis or ongoing cardiac ischemia. In a patient with newly diagnosed anemia of uncertain etiology,obtain laboratory studies for hematologic evaluation before transfusion. Consultation with a hematologistmay be beneficial to guide this evaluation. The subsequent evaluation of some patients with chronicanemias or anemias of uncertain etiology can be made more di�icult by transfusion, so transfusion shouldnot be undertaken unless specifically indicated.

Treatment for nutritional deficiency anemias usually produces a reticulocyte response in 4 to 7 days (TableTable231-4231-4). Standard therapy for iron or folate deficiency uses oral replacement. Vitamin B12 replacement has

traditionally been intramuscular because of concern that malabsorption of the vitamin, a common

predisposing condition for vitamin B12 deficiency, would limit the e�ectiveness of oral replacement.22

However, oral doses of 2000 micrograms of vitamin B12 per day are as e�ective as the intramuscular route in

achieving the desired clinical response.23,24

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TABLE 231-4

Treatment for Specific AnemiasTreatment for Specific Anemias

Anemia TypeAnemia Type Treatment (Adult Doses)Treatment (Adult Doses)

Iron deficiency

anemia

Elemental iron, 200–300 milligrams PO daily (e.g., ferrous sulfate, 325 milligrams PO, 3–4

tablets taken on an empty stomach over the course of day); reticulocyte count should

increase within 4–7 d and peak at 10 d; sustained treatment a�er correction of anemia is

usually necessary to replenish iron stores.

Cyanocobalamin

(vitamin B12)

deficiency

anemia

Cyanocobalamin, 1000 micrograms IM per week for 8 wk and every month therea�er;

reticulocyte count should increase within 4 d and peak at 7 d. Oral replacement with 2000

micrograms daily is also e�ective (see "Treatment" section).

Folate

deficiency

anemia

Folate, 1 milligram PO daily (doses up to 5 milligrams may be needed for patients with

malabsorption); reticulocyte count should increase within 4 d with normalization of

hemoglobin level in 1–2 mo.

Sideroblastic

anemia

Evaluate for reversible causes, including alcohol or other drug toxicity, or toxin exposure.

Discontinue any o�ending agents. Treatment is mainly supportive, consisting primarily of

blood transfusions to maintain the hemoglobin level. A trial of pyridoxine at

pharmacologic doses (500 milligrams PO daily) may be helpful, with response most

commonly seen in cases resulting from ethanol abuse or the use of pyridoxine

antagonists. Some patients with hereditary, X-linked sideroblastic anemia also respond

to pyridoxine. Improvement with pyridoxine is rare for sideroblastic anemia of other

causes.

Aplastic anemia Supportive care, including transfusion if appropriate. Referral for further workup.

Anemia of

chronic disease

Supportive care, including transfusion if appropriate. Referral for further workup and

evaluation for underlying disease.

DISPOSITION AND FOLLOW-UPDISPOSITION AND FOLLOW-UP

Patients with anemia from ongoing blood loss should be admitted to the hospital for further evaluation andtreatment. Patients with isolated anemia that is chronic or newly diagnosed and not related to blood loss donot necessarily require hospital admission if they are asymptomatic and hemodynamically stable, they haveminimal comorbid disease, and close follow-up can be arranged. Patients newly diagnosed with anemia who

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1. 

2. 

3. 

4. 

5. 

6. 

7. 

8. 

9. 

10. 

also have abnormalities in the WBC or platelet count should have hematologic consultation and shouldprobably be admitted.

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