Anemia In The Emergency
Department: Evaluation And
Treatment
Anemia is a common worldwide problem that is associated with
nonspecific complaints. The initial focus for the emergency evaluation of anemia is to determine whether the problem is acute or
chronic. Acute anemia is most commonly associated with blood
loss, and the patient is usually symptomatic. Chronic anemia is
usually well tolerated and is often discovered coincidentally. Once
diagnosed, the etiology of anemia can often be determined byapplying a systematic approach to its evaluation. The severity of
the anemia impacts clinical outcomes, particularly in critically illpatients; however, the specific threshold to transfuse is uncertain.
Evaluation of the current literature and clinical guidelines does
not settle this controversy, but it does help clarify that a restrictive
transfusion strategy (ie, for patients with a hemoglobin < 6-8 g/dL) is associated with better outcomes than a more liberal transfusion strategy. Certain anemias may have well-defined treatment
options (eg, sickle cell disease), but empiric use of nutritional
supplements to treat anemia of uncertain etiology is discouraged.

Andy Jagoda, MD, FACEP
Professor and Chair, Department ofEmergency Medicine, Icahn Schoolof Medicine at Mount Sinai, Medical
Director, Mount Sinai Hospital, New
York, NY

Associate Editor-In-Chief
Kaushal Shah, MD, FACEP
Associate Professor, Department ofEmergency Medicine, Icahn Schoolof Medicine at Mount Sinai, New
York, NY

Editorial Board
William J. Brady, MD
Professor of Emergency Medicine
and Medicine, Chair, Medical
Emergency Response Committee,
Medical Director, Emergency
Management, University of Virginia
Medical Center, Charlottesville, VA
Peter DeBlieux, MD 		
Professor of Clinical Medicine,Interim Public Hospital Directorof Emergency Medicine Services,Louisiana State University Health
Science Center, New Orleans, LA

Authors

Timothy G. Janz, MD, FACEP, FCCP

Professor, Department of Emergency Medicine, Pulmonary/Critical
Care Division, Department of Internal Medicine, Boonshoft School of
Medicine, Wright State University, Dayton, OH

Roy L. Johnson, MD, FAAEM

Abstract

Editor-In-Chief

November 2013

Volume 15, Number 11

of Medicine at Mount Sinai, New
York, NY
Michael A. Gibbs, MD, FACEP
Professor and Chair, Departmentof Emergency Medicine, Carolinas
Medical Center, University of North
Carolina School of Medicine, Chapel
Hill, NC
Steven A. Godwin, MD, FACEP
Professor and Chair, Departmentof Emergency Medicine, AssistantDean, Simulation Education,
University of Florida COMJacksonville, Jacksonville, FL
Gregory L. Henry, MD, FACEP
Clinical Professor, Department ofEmergency Medicine, Universityof Michigan Medical School; CEO,
Medical Practice Risk Assessment,
Inc., Ann Arbor, MIJohn M. Howell, MD, FACEP
Clinical Professor of Emergency
Medicine, George Washington
University, Washington, DC; Directorof Academic Affairs, Best Practices,Inc, Inova Fairfax Hospital, Falls
Church, VA

Attending Physician, Massachusetts
General Hospital, Boston, MA

Assistant Professor, Associate Program Director, Integrated
Residency in Emergency Medicine, Boonshoft School of Medicine,
Wright State University, Dayton, OH

Scott D. Rubenstein, MD, MS, EMT-T

Chief Resident, Wright State University/Wright-Patterson Air Force
Base Combined Emergency Medicine Residency, Dayton, OH
Peer Reviewers

David Cherkas, MD, FACEPAssistant Professor of Emergency Medicine, Icahn School of
Medicine at Mount Sinai, New York, NY

Chad Meyers, MD

Director, Emergency Critical Care, Bellevue Hospital Center;
Assistant Professor of Clinical Emergency Medicine, New York
University School of Medicine, New York, NY
CME Objectives
Upon completion of this article, you should be able to:
1.
2.
3.

Differentiate between the 3 categories of anemia when
considering a differential diagnosis.

Describe the diagnostic workup for patients presenting to the
ED with anemia.
Summarize the general principles of transfusion therapy.

Prior to beginning this activity, see “Physician CME Information” on
the back page.
Icahn School of Medicine at Mount
Sinai, New York, NY

Scott Silvers, MD, FACEPCharles V. Pollack, Jr., MA, MD,
Chair, Department of Emergency
FACEP
Medicine, Mayo Clinic, Jacksonville, FL
Professor and Chair, Department ofEmergency Medicine, Pennsylvania
Corey M. Slovis, MD, FACP, FACEP
Hospital, Perelman School ofProfessor and Chair, Department
Medicine, University of Pennsylvania,
of Emergency Medicine, Vanderbilt
Philadelphia, PA
University Medical Center; Medical
Michael S. Radeos, MD, MPH
Director, Nashville Fire Department andAssistant Professor of Emergency
International Airport, Nashville, TN
Medicine, Weill Medical College
StephenH. Thomas, MD, MPH
of Cornell University, New York;
George Kaiser Family Foundation
Research Director, Department ofProfessor & Chair, Department ofEmergency Medicine, New York
Emergency Medicine, University of
Hospital Queens, Flushing, NY
Oklahoma School of Community
Ali S. Raja, MD, MBA, MPH
Medicine, Tulsa, OK
Director of Network Operations andBusiness Development, Department Ron M. Walls, MD
Professor and Chair, Department ofof Emergency Medicine, Brigham
Emergency Medicine, Brigham andand Women’s Hospital; Assistant
Women’s Hospital, Harvard Medical
Professor, Harvard Medical School,
School, Boston, MA
Boston, MA
Scott D. Weingart, MD, FCCM
Robert L. Rogers, MD, FACEP,
Associate Professor of Emergency
FAAEM, FACP
Medicine, Director, Division ofAssistant Professor of Emergency
ED Critical Care, Icahn School of
Medicine, The University of
Medicine at Mount Sinai, New
Maryland School of Medicine,York, NY
Baltimore, MD

Shkelzen Hoxhaj, MD, MPH, MBA
Chief of Emergency Medicine, Baylor
Francis M. Fesmire, MD, FACEP
College of Medicine, Houston, TX
Alfred Sacchetti, MD, FACEP
Professor and Director of Clinical
Assistant Clinical Professor,
Research, Department of Emergency Eric Legome, MD
Department of Emergency Medicine,
Medicine, UT College of Medicine,
Chief of Emergency Medicine,Thomas Jefferson University,
Chattanooga; Director of Chest Pain
King’s County Hospital; Professor ofPhiladelphia, PA
Center, Erlanger Medical Center,
Clinical Emergency Medicine, SUNY
Chattanooga, TN
Robert Schiller, MD
Downstate College of Medicine,
Chair, Department of Family
Brooklyn, NY
Nicholas Genes, MD, PhD
Medicine, Beth Israel Medical
Keith A. Marill, MD
Assistant Professor, Department ofCenter; Senior Faculty, Family
Assistant Professor, Harvard Medical
Emergency Medicine, Icahn School
Medicine and Community Health,
School; Emergency Department

Senior Research Editors
James Damilini, PharmD, BCPS
Clinical Pharmacist, Emergency
Room, St. Joseph’s Hospital andMedical Center, Phoenix, AZ
Joseph D. Toscano, MD
Chairman, Department of Emergency
Medicine, San Ramon Regional
Medical Center, San Ramon, CA

Research Editor
Michael Guthrie, MD
Emergency Medicine Residency,
Icahn School of Medicine at Mount
Sinai, New York, NYInternational Editors
Peter Cameron, MD
Academic Director, The Alfred
Emergency and Trauma Centre,
Monash University, Melbourne,
Australia
Giorgio Carbone, MD
Chief, Department of Emergency
Medicine Ospedale Gradenigo,
Torino, Italy
Amin Antoine Kazzi, MD, FAAEM
Associate Professor and Vice Chair,
Department of Emergency Medicine,
University of California, Irvine;
American University, Beirut, Lebanon
Hugo Peralta, MD
Chair of Emergency Services,
Hospital Italiano, Buenos Aires,
Argentina
Dhanadol Rojanasarntikul, MD
Attending Physician, Emergency
Medicine, King Chulalongkorn
Memorial Hospital, Thai Red Cross,
Thailand; Faculty of Medicine,
Chulalongkorn University, Thailand
Suzanne Peeters, MD
Emergency Medicine Residency
Director, Haga Hospital, The Hague,
The Netherlandspositive fecal occult blood test on digital rectal examination. The patient’s ECG is consistent with rate-controlled
atrial fibrillation and shows ST-segment depression in
the lateral leads. The CBC reveals a hemoglobin of 4.9 g/
dL and a hematocrit of 15.2%, with a normal WBC andplatelet count, PT, INR, and aPTT. His basic chemistry
panel reveals an elevated BUN of 64 mg/dL and a creatinine of 2.3 mg/dL. The troponin is within the normal
range. A normal saline bolus of 500 cc is administered.
As you call cardiology, you wonder: what is the optimaltreatment for this patient’s presentation… cardiac catheterization or transfusion?
Just as you think you are getting control of the ED, a
6-month-old boy is brought in by his parents for congestion, increased work of breathing, and perioral cyanosis.
The parents state that their child is taking longer to feed
because he seems to be out of breath. This has been goingon for several weeks, and they are unsure if their child has
had a fever; they do not have a thermometer or a pediatrician. The patient was born at home with a midwife. The
child’s vital signs are: blood pressure, 70/50 mm Hg; heartrate, 155 beats/min; respiratory rate, 53 breaths/min;
SpO2, 92% on room air. He is afebrile. On your examination, the child is alert and responsive, but he is small for
his age. He cries at appropriate aspects of the physicalexamination and is easily consoled by his mother. He istachypneic with bilateral faint rales but does not demonstrate retractions or nasal flaring. The patient’s face isdysmorphic. His skin has a yellow hue with scleral icterus
and perioral cyanosis and acrocyanosis. On abdominal
examination, he has significant hepatosplenomegaly. The
rest of his physical exam is unremarkable. A basic chemistry panel is otherwise normal; however, his CBC reveals ahemoglobin of 7.8 g/dL, with a normal WBC and platelet
count. The mean corpuscular volume is 75.4 fL, mean
corpuscular hemoglobin concentration is 29.1%, and red
cell distribution width is 16.2%. A chest radiograph issuggestive of pulmonary congestion. Pediatrics isn’t yourstrength, and you wonder: why is this child anemic, andwhat are my next steps?

Case Presentations
A 54-year-old Hispanic male presents to the ED with thecomplaints of fatigue and weakness. The weakness is described as generalized, and the symptoms have been present and constant for the last 2 days. The patient denies
hematemesis, hematochezia, dark-colored stools, hematuria, or other evidence of bleeding. He also denies chest or
abdominal pain, dyspnea, diaphoresis, fever, or chills. The
patient has not seen a doctor in the last 15 years and does
not think he has any medical conditions. The only medication he has been taking is over-the-counter ibuprofen,
which he has been taking daily since he injured his backat work 2 weeks ago. The patient works as a construction
laborer and denies past surgeries or allergies. His vital
signs are: blood pressure, 110/50 mm Hg; heart rate, 127
beats/min; respirations, 22 breaths/min; and SpO2, 97%
on room air. The patient is afebrile. His skin is warm anddry but, despite being dark-skinned, he appears a little
pale. On eye examination, the sclerae appear to have ayellow hue. Cardiovascular examination reveals bounding
pulses, a hyperdynamic precordium, and a grade II overVI soft, systolic murmur. The remainder of the examination is unremarkable, including a rectal examination,
which is negative for occult blood. An ECG shows a sinus
tachycardia but is otherwise normal. A basic chemistry
panel is within normal limits; however, the CBC reveals ahemoglobin of 5.4 g/dL, hematocrit of 16%, WBC of 8000,
and platelet count of 154,000. Based on the presenting
symptoms and signs, the patient is likely to need RBC
transfusions. An IV catheter is placed, and a normal saline infusion is initiated. A 500-mL bolus of normal saline
reduces the heart rate to 105 beats/min. As you write
the order for the transfusion, your nurse asks, “What is
the goal for the transfusion and what is the cause of theanemia?” You think, “Good questions!”
In the next room, there is a 68-year-old male who reports 1 week of increasing weakness, dyspnea on exertion,and mild chest pressure. He states the reason for coming
in today is that his chest pressure was substantially worse
and was associated with diaphoresis. The patient has ahistory of atrial fibrillation (rate controlled) and has been
taking dabigatran for the past 2 years. The patient denies
hematemesis but has a history of dark stools. However, hestates that he was placed on iron supplementation by his
primary care physician over a year ago. He denies backpain, abdominal pain, fevers, chills, or focal neurologicalcomplaints. The patient has no known drug allergy anddenies past surgeries, but he does have a history of hypertension and chronic anemia in addition to atrial fibrillation. Based on his chief complaints, an ECG, CBC, BMP,
PT/INR, portable chest radiograph, and 325 mg of aspirin
are ordered. His vital signs are: temperature, 37°C; bloodpressure, 105/65 mm Hg; heart rate, 105 beats/min;
respirations, 26 breaths/min; and SpO2, 94% on room air.
Overall, the patient’s examination is unremarkable except
for an irregularly irregular heart rate accompanied by asoft blowing systolic murmur, pale conjunctiva, and a
Emergency Medicine Practice © 2013

Introduction
Anemia is defined as an absolute decrease in thenumber of circulating red blood cells (RBCs). The
diagnosis of anemia is based upon laboratory measurements of RBC indices that fall below accepted
normal values. (See Table 1.) It is the most common

Table 1. Normal Values

2

Age

Hemoglobin(g/dL)

Hematocrit(%)

Red Blood Cell
Count (x 106/mcL)

3 months

10.4-12.2

30-36

3.4-4.0

3-7 years

11.7-13.5

34-40

4.4-5.0

Adult man

14.0-18.0

40-52

4.4-5.9

Adult woman

12.0-16.0

35-47

3.8-5.2

www.ebmedicine.net • November 2013

hematologic disorder, and it is a global health problem. Worldwide, anemia affects 24.8% of the population and is more prevalent in children and pregnant
women.1 The prevalence of anemia varies depending on the RBC indices used to define it. In theAmericas, anemia affects 29% of preschool children
and 24% of pregnant women.1 Another age groupassociated with an increased incidence of anemia isthe elderly (defined as age ≥ 65 years). From a 2010
prospective population-based study of 8744 elderly
individuals, the prevalence of anemia was 11%.2
Data on the frequency of anemia in the emergency department (ED) are less robust. Anemia occurs
in 9% to 14% of pediatric ED patients and 14% ofobstetric ED patients.3-5 Data defining the frequency
of its occurrence in the general ED population islacking. In emergency medicine, anemia is divided
into 2 broad categories: acute, with potential lifethreatening complications; and chronic, with morestable clinical presentations. The focus of this issueof Emergency Medicine Practice is the ED evaluationof anemia and, more importantly, its management
based on the best available evidence in the literature.

of the major components usually results in compensatory changes in the other 2 components. As an
example, a decrease in hemoglobin is compensatedby both inotropic and chronotropic cardiac changes
that result in increased blood flow and a decreased
hemoglobin affinity at the tissue level, thereby allowing the release of more oxygen. These compensatory responses may fail because of disease severity
or underlying pathologic conditions. The result offailed compensatory responses is tissue hypoxia, cellular dysfunction, and eventual cell death.
Anemia often stimulates the compensatory
mechanism of erythropoiesis controlled by the hormone erythropoietin. Erythropoietin is a glycoprotein produced primarily in the kidney. It regulates
the production of RBCs by controlling differentiation of the committed erythroid stem cell. Erythropoietin is stimulated by tissue hypoxia and byproducts of RBC destruction. Erythropoietin levels areelevated in many types of chronic anemia.6
Bone marrow contains pluripotent stem cells
that differentiate into erythroid, myeloid, megakaryocytic, and lymphoid progenitors. Erythropoietin stimulates the growth and differentiationof erythroid progenitors. When the normoblast extrudes its nucleus, it retains its ribosomal network,
which identifies the reticulocyte. The reticulocyte
will keep its ribosomal network for approximately
4 days, 3 of which are normally spent in the bonemarrow and 1 in the peripheral circulation. The
RBC develops as the reticulocyte loses its ribosomal
network, and the mature RBC circulates for 110
to 120 days. The old erythrocytes are removed bymacrophages that detect senescent signals. Under
steady-state conditions, the rate of RBC production
equals the rate of destruction. The mass of RBCs
remains constant because an equal number of reticulocytes replace the destroyed senescent erythrocytes during the same period.6
Common sites of unrecognized blood loss fromtrauma include the pleural, peritoneal, pelvic, andretroperitoneal spaces. In addition to trauma, risk
factors for blood loss include hereditary and acquired abnormalities to platelets and the coagulation
system. This is especially true for the elderly, who
are more likely to be taking anticoagulants and antiplatelet agents.7,8 In nontraumatic situations of blood
loss, the gastrointestinal tract, retroperitoneal space,
peritoneal space, and pelvis must be considered.9
Causes other than blood loss may be responsible
for severe anemia of rapid onset. Rare hemolytic
conditions can cause rapid destruction of RBCs.
(See Table 2, page 4.) More commonly, patients withchronic compensated hemolytic anemia (eg, sickle
cell disease) have more stable anemias.
Beyond red cell production and destruction, thestatus of hemoglobin function must be considered.
Impaired hemoglobin transport of oxygen is seen in

Critical Appraisal Of The Literature
A literature search of PubMed was performed
using the search terms anemia, transfusion, transfusion threshold, and emergency department. Studies
within the last 12 years were analyzed and included
reviews, case reports, case series, and prospective
randomized trials. More than 300 articles werereviewed, and 57 were selected for inclusion in thisissue. In addition, data from the National Guideline Clearinghouse and the Cochrane Database of
Systematic Reviews were used. The literature, muchof it observational in form, shows that hemoglobin
levels < 6 g/dL, especially in acute anemia, are associated with worse outcomes compared to individuals with hemoglobin levels above this value. On
the other hand, the literature has also shown thatthe use of RBC transfusions is associated with pooroutcomes. Randomized controlled studies showthat using a restrictive transfusion strategy (defined
as a transfusion hemoglobin threshold of < 6-8 g/dL) is associated with better outcomes than using aliberal strategy (defined as a transfusion hemoglobin
threshold of < 9-10 g/dL). However, the hemoglobin level that should be the endpoint of transfusion
therapy still has not been defined in the literature.

Etiology And Pathophysiology
The major function of the RBCs is to transport oxygen from the lungs to the tissues and transport carbon dioxide in the reverse direction. Oxygen transport is influenced by the amount of hemoglobin, its
oxygen affinity, and blood flow. An alteration in any
November 2013 • www.ebmedicine.net

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Emergency Medicine Practice © 2013

patients with carbon monoxide poisoning. Methemoglobinemia from nitrates, cyanohemoglobin fromcyanide, and sulfhemoglobinemia resulting fromhydrogen sulfide can severely decrease functionalhemoglobin. These patients often present withsymptoms associated with anemia, such as fatigue,
altered mental status, shortness of breath, and othermanifestations of hypoxia, but without signs of RBC
loss or volume depletion.10

in the ED, but replacement of iron, vitamin B12,or folate without a definitive diagnosis should be
avoided, especially the use of supplemental iron.
RBC indices are useful in classifying anemias
caused by a production deficit. Their calculation
formulas and normal ranges are provided in Table
3. Mean corpuscular volume (MCV) is a measureof RBC size. Decreases in MCV define microcytosis
and increases reflect macrocytosis. Mean corpuscular hemoglobin (MCH) incorporates both RBC
size and hemoglobin concentration. The MCH
concentration is a measure of the concentration ofhemoglobin. Low values represent hypochromia,
whereas high values are noted in patients withdecreased cell membrane relative to cell volume(such as spherocytosis). An additional index is the
RBC distribution width (RDW), which is a measureof the homogeneity of the RBCs measured.6,10

Differential Diagnosis
The differential diagnosis of anemia is facilitated byclassifying the anemia into 1 of 3 groups: (1) blood
loss, (2) decreased RBC production, or (3) increased
RBC destruction. A complementary approach basedon RBC morphology and indices is often used.10(See the Clinical Pathway, page 8.) Anemia secondary to acute blood loss is characterized by reduced
hemoglobin value with normal RBC indices.

Microcytic Anemias
Hypochromic microcytic anemias are subdivided
into deficiencies of the 3 components of hemoglobin:(1) iron (iron-deficiency anemia), (2) globin (thalassemia), and (3) porphyrin (sideroblastic anemia
and lead poisoning). Anemia of chronic disease, asecondary iron abnormality, is the last of the microcytic anemias. It must be remembered that not all
microcytic anemias are the result of iron deficiency,
and routine iron therapy for a patient with a low
MCV and mean corpuscular hemoglobin concentration (MCHC) should be avoided.10

Decreased Red Blood Cell Production

Anemias caused by decreased RBC production
have an insidious onset and are associated witha decreased reticulocyte count. The RBC indicesand morphology manifested in a peripheral smear
are useful in making the diagnosis. The definitive
diagnosis is not usually made in the ED, and it may
require bone marrow examination. In general, theemergency clinician does not initiate replacement
therapy except in circumstances that require transfusion. Appropriate diagnostic tests may be ordered

Iron-Deficiency Anemia

Iron deficiency is a frequent cause of chronic anemia
seen in the ED, and it is usually occult in presentation. The diagnosis is made by laboratory evaluationof the fasting levels of serum iron, serum ferritin,and the total iron-binding capacity. Occult blood
loss (especially gastrointestinal) may initially appear
as iron-deficiency anemia. Therefore, a concentrated
search for occult blood loss is vital.

Table 2. Common Causes Of Hemolysis
Extravascular Destruction• Intrinsic Red Blood Cell Defectslll

Enzyme deficiencies (eg, glucose-6-phosphate dehydrogenase
deficiency)
Hemoglobinopathies (eg, sickle cell disease, thalassemia)

Membrane defects (eg, elliptocytosis, hereditary spherocytosis)

Table 3. Red Blood Cell Indices• Extrinsic Red Blood Cell Defects
l

l

l

l

l

Autoimmune hemolytic anemia
Liver disease

Infections (eg, malaria, Bartonella)

Toxins (eg, nitrates, dapsone, aniline dyes, snake and spider
bites)

l

		
l

l

l

Formula for Calculation

Normal Range

MCV

Hematocrit x 10/RBC
count

81-100 fL

MCH

Hemoglobin x 10/RBC
count

26-34 pg

MCHC

Hemoglobin x 100/hematocrit

31%-36%RDW

Standard deviation of
MCV/MCV x 100

11.5%-14.5%

Hypersplenism

Intravascular Destruction
l

Index

Transfusion reactions

Microangiopathic trauma (eg, prosthetic heart valves, aortic
stenosis, thrombotic thrombocytopenic purpura, disseminatedintravascular coagulation)
Infection (eg, sepsis)

Abbreviations: MCH, mean corpuscular hemoglobin; MCHC, mean
corpuscular hemoglobin concentration; MCV, mean corpuscularvolume; RDW, red blood cell distribution width.

Paroxysmal nocturnal hemoglobinuria
Heat damage

Emergency Medicine Practice © 20134www.ebmedicine.net • November 2013

ritin levels. This anemia can be differentiated fromiron deficiency by the total iron-binding capacity
and the serum ferritin level. Because the hematocrit
is seldom < 25% to 30%, these patients are often
asymptomatic and therapy is not usually required.
Any of several chronic comorbid disease states is theunderlying cause of the anemia.13

Thalassemia

Thalassemia is a genetic autosomal defect associatedwith the decreased synthesis of globin chains. The
hemoglobin molecule is present as 2 paired globin
chains. Each type of hemoglobin is made up of different globins: normal adult hemoglobin is made upof 2 alpha chains and 2 beta chains (alpha2 and beta2),
and fetal hemoglobin (HbF) is alpha2 gamma2. A separate autosomal gene controls the production of each
globin chain. Decreased globin production in thalassemia results in a decreased hemoglobin synthesis
and ineffective erythropoiesis. The ineffective erythropoiesis results in increased intramarrow hemolysis
with destruction of RBCs before they are released.6,10
Homozygous beta-chain thalassemia (thalassemia major) occurs predominantly in populationsof Mediterranean origins and represents one of themost common single-gene disorders. The disease ischaracterized by severe anemia, hepatosplenomegaly, jaundice, abnormal childhood development, andpremature death. Patients are dependent on bloodtransfusions and often die from iron toxicity.11,12
Heterozygous beta-chain thalassemia (thalassemia minor) is manifested as a mild microcytic hypochromic anemia with associated target cells seen on
the peripheral blood smear. These patients are usuallyasymptomatic, and no treatment is necessary.6,10

Macrocytic Anemia
The most important cause of macrocytic anemia is
the megaloblastic form. Megaloblastic anemia is thehematologic manifestation of a total-body alteration
in DNA synthesis caused by a lack of vitamin B12
and folic acid. The deficiency affects tissues with
rapid cell turnover, including hematopoietic cells
and those of mucosal surfaces, particularly in thegastrointestinal tract. Hematopoietically, this deficiency is characterized by ineffective erythropoiesis
and pancytopenia. The differentiation between folate
and vitamin B12 deficiencies usually depends on
measured serum levels.6,10
A unique feature of vitamin B12 deficiency is neurologic involvement. The classic neurologic complex
includes loss of proprioception, weakness and spasticity of the lower extremities with altered reflexes,
and variable mental changes. The latter 2 complaints
may also be seen in folic acid deficiency.6,10
Macrocytic anemia is suggested when the MCV
is > 100 fL. Large oval red cells (macro-ovalocytes)
and hypersegmented polymorphonuclear neutrophils seen on the peripheral blood smear are
believed to be diagnostic for megaloblastic anemias. Other useful laboratory tests include levelsof vitamin B12, folate, red cell folate, and lactate
dehydrogenase (LDH).6,10 Liver disease, often associated with alcoholism, is the most common causeof macrocytic anemia. Macrocytic target cells may
be seen on the peripheral smear in conjunction withthis disorder. Hypothyroidism and hemolysis may
also present as a macrocytic anemia.

Sideroblastic Anemia

Sideroblastic anemia involves a defect in porphyrin
synthesis and results in excess iron being depositedin the mitochondria of the RBC precursor. Defective
heme synthesis results in ineffective erythropoiesis,
mild to moderate anemia, and a dimorphic peripheral smear with hypochromic microcytes, along withnormal and macrocytic cells. Sideroblastic anemia
can be secondary to a rare sex-linked hereditaryform, but it is more often a disease of the elderly.
Pallor and splenomegaly may be noted, and the
peripheral smear may demonstrate iron-containing
inclusion bodies in RBCs. Idiopathic sideroblastic
anemia is considered a preleukemic state, and acute
myelogenous leukemia develops in approximately
5% of these patients. Secondary causes of sideroblastic anemia include toxins such as chloramphenicol,
isoniazid, and cycloserine as well as diseases suchas hemolytic and megaloblastic anemia, infection,
carcinoma, leukemia, and rheumatoid arthritis. The
exact mechanisms of these causative agents and diseases are unknown. Lead poisoning is one reversible
cause of sideroblastic anemia. Elevated blood leadlevels are diagnostic.

Normochromic And Normocytic Anemias
The origin of normochromic and normocytic anemia
secondary to decreased production is not as obvious as that of macrocytic and microcytic anemias.
Since reticulocytes reflect RBC production in bonemarrow, one hematologic parameter that can aid in
the diagnosis of normocytic anemia associated withhypoproduction is the corrected reticulocyte count.
Low reticulocyte counts reflect depressed bone marrow production. Normocytic anemia can be classified as being due to primary bone marrow involvement or a secondary marrow response to underlying
disease. Aplastic anemia, myelophthisic anemia, andmyelofibrosis are examples of normochromic andnormocytic anemias.

Anemia Of Chronic Disease

Anemia of chronic disease is common and is usually
normochromic and normocytic. This form of anemia
is characterized by low serum iron levels, low totaliron-binding capacity, and normal or elevated ferNovember 2013 • www.ebmedicine.net

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Emergency Medicine Practice © 2013

Increased Red Blood Cell Destruction

tibodies are IgM in nature and, consequently, cause
intravascular hemolysis.
Another set of antigens on the RBC is the Rh
system. This system is unique in that individuals
do not have antibodies that correspond to Rh antigens unless they have been sensitized by previous
exposure to these antigens. The antibodies produced are IgG in nature and accelerate extravascular destruction of RBCs within the spleen and liver.
Most autoimmune antibodies are directed toward
antigens in the Rh system.

The hemolytic anemias are defined by a shortened life
span of the erythrocyte and can be acute or chronic
in form. In their acute form, hemolytic anemias canbe life-threatening and require rapid diagnosis andintervention. Fortunately, they are relatively rarecompared to chronic hemolytic conditions. Chronic
disorders may be related to primary blood disorders(eg, sickle cell anemia) or may be a result of otherdisease states (eg, chronic renal failure).
The clinical signs and symptoms of hemolytic
anemia are caused by either intravascular or extravascular hemolysis. Intravascular hemolysis is usually associated with an acute and dramatic presentation. Large numbers of RBCs may be lysed within
the circulation, and free hemoglobin initially binds
to haptoglobin and hemopexin. These complexes
are transported to the liver, converted to bilirubin,
conjugated, and excreted. When the binding andtransport system is overwhelmed, free hemoglobin
may appear in the blood.6,10
The clinical appearance of intravascular hemolysis may vary from mild chronic anemia to prostration, fever, abdominal and back pain, and mental
changes, as seen with transfusion reactions. Jaundice, brown to red urine, and oliguria induced by
the hemoglobin complex can also occur.6,10
Extravascular hemolysis is more common andclinically better tolerated than intravascular hemolysis. Primary splenic overactivity, antibody-mediatedchanges, or RBC membrane abnormalities may
cause normal splenic function to increase to pathologic levels. Hemolysis may also occur within thebone marrow.14 The clinical picture of extravascular hemolysis is usually mild to moderate anemia,
jaundice, and splenomegaly; however, the signs andsymptoms vary with the severity and chronicity of
the hemolysis. Because extravascular hemolysis is
not associated with myoglobinuria or hemoglobinuria, the urine will appear normal in color or havean orange hue secondary to elevated bilirubin.
Sickle cell disease is the most common hemolytic anemia presenting to the ED. The emergency
clinician should be familiar with this disease process. Even experienced physicians may overlook its
major complications. Physicians with less experience may fail to recognize the complexity of thisdisease and the many potential complications.15 For
more information on managing patients with sickle
cell disease, see the August 2011 issue of Emergency
Medicine Practice, “Evidence-Based Management Of
Sickle Cell Disease In The Emergency Department.”

Extrinsic Autoantibodies
The major feature of autoimmune hemolysis is the
production of an IgG or IgM antibody to an antigen present on the RBC membrane. Autoimmune
hemolytic anemias are acquired disorders, with 40%
to 50% being idiopathic. The remainder are associated with a number of diseases. (See Table 2, page4.) Classification of autoimmune hemolytic anemias
is based on the optimal temperature at which theantibody reacts with the RBC membrane. Therefore, there are warm-reacting (> 37°C) and coldreacting (< 37°C) antibodies. The direct antiglobulin(Coombs) test helps differentiate the warm-reactingfrom the cold-reacting. The Coombs test is positive
with warm-reacting antibodies and characterizes an
autoimmune hemolytic anemia.10,14
Extrinsic Mechanical Causes
The peripheral blood smear may demonstrateschistocytes or fragmented RBCs, which shouldraise the suspicion of traumatic injury. Microangiopathic hemolytic anemia, cardiac trauma, andexercise-induced hemoglobinemia are the mostcommonly encountered forms of traumatic hemolysis. Microangiopathic hemolytic anemia is a form of
microcirculatory fragmentation by fibrin depositedin the arterioles. It may be found in preeclampsia,
vasculitis, thrombotic thrombocytopenic purpura,disseminated intravascular coagulation, and vascular anomalies. The signs and symptoms are those of
intravascular hemolysis, and treatment is directed at
the underlying cause.
Increased cardiac blood turbulence can cause
trauma to RBCs. It is most commonly found inpatients with prosthetic valves but can also be associated with traumatic arteriovenous fistula, aortic
stenosis, and other left-sided heart lesions.
March hemoglobinemia is a form of trauma
caused by breaking of intravascular RBCs by repetitive pounding. Soldiers, marathon runners, and anyone with repetitive striking against a hard surface
may incur this problem.16

Extrinsic Alloantibodies
Alloantibodies are formed in response to foreign
RBC antigens, and the ABO system is one of themost important RBC wall antigens. ABO incompatibility can be a life-threatening reaction. These anEmergency Medicine Practice © 2013

Abnormal Sequestration
Hypersplenism can be caused by any disease thatenlarges the spleen or stimulates the reticuloen6

www.ebmedicine.net • November 2013

complaints may include irritability, headache,postural dizziness, chest pain, decreased exercise
tolerance, and dyspnea on exertion. When the anemia is of slow onset, the patient may adapt until thehemoglobin is very low, and they may have minimal complaints. The presence of easy bleeding may
suggest a platelet or coagulation disorder. Jaundice,scleral icterus, or splenomegaly in the setting ofanemia should alert the physician to the possibilityof a hemolytic process. Neurologic symptoms (suchas paresthesias, ataxia, or altered mental status) may
suggest a megaloblastic anemia. A history about disorders known to be associated with anemia, such as
renal failure, hepatic disease, hypothyroidism, andcollagen vascular disease, should also be obtained.18
If anemia is suggested by the history, a thoroughphysical examination should be conducted. However, many patients with mild to moderate anemia
will have a normal physical examination. The presence of tachycardia, bounding cardiac impulse, andfunctional systolic murmur may suggest a significant anemia. Pallor in the nail beds, face, palms, andconjunctivae is associated with significant anemia.
Jaundice, splenomegaly, and scleral icterus are often
seen in hemolytic anemias. Abnormal findings on
neurologic examination may suggest folate or vitamin B12 deficiency. The presence of petechiae or ecchymosis suggests bleeding disorders that may haveassociated anemia. Generalized lymphadenopathy
and hepatomegaly are also important physical findings that may be accompanied by anemia. Althoughphysical findings are important, the ability to actually diagnose anemia based on physical examination
is limited.19-21

dothelial system. The enlarged spleen traps blood
components, which contributes to the splenomegaly.
Splenic sequestration should be suspected in thesetting of splenomegaly, pancytopenia, and marrow
hyperactivity (elevated reticulocyte count).6,10

Prehospital Care
The role of emergency medical services (EMS) providers in the setting of anemia is limited. EMS is likely to
be involved if the anemia is secondary to blood loss
(particularly acute loss) or symptoms related to anunderlying anemia. At times, the patient may alreadyhave a diagnosed anemia (such as sickle cell disease)and is presenting with an apparent complicationof such. EMS providers can be particularly helpful
in obtaining historical information, especially if thepatient is unable to give an accurate history. Examples
of key information from prehospital providers may
include the presence of blood, coffee-ground emesisor an odor of digested blood at the scene, the presenceof pill bottles at the scene (particularly antiplatelet
or anticoagulant drugs), and the location or occupation of the patient (eg, an industrial site or site where
chemical exposure is possible).17

Emergency Department Evaluation
Blood loss is the most common cause of clinicallysignificant anemia.1-4 The clinical manifestation ofanemia depends on how rapidly the hematocrit
decreases and on the patient’s ability to compensate.
Clinical signs and symptoms of blood loss potentially include tachycardia, hypotension, postural
hypotension, and tachypnea. Complaints of thirst,
light-headedness, syncope or near-syncope, weakness, altered mental status, and decreased urine output may also be present. Age, concomitant illness,and underlying hematologic, cerebral, and cardiovascular status tremendously influence the clinicalfindings. Children and young adults may toleratesignificant blood loss with unaltered or minimallyaltered vital signs until a precipitant hypotensive
episode occurs. Elderly patients commonly have underlying disease states that compromise their ability
to compensate for blood loss.18
A history of trauma or clinical evidence of bleeding, such as hematochezia, hematemesis, hematuria,
or menorrhagia, is often present. However, featuresless obvious to the patient (such as melena, history of peptic ulcer disease, chronic liver disease,or bleeding diathesis) should also be asked about.
Antacids, H2 blockers, proton pump inhibitors,
nonsteroidal anti-inflammatory drugs, antiplatelet
agents, and anticoagulants are medications that may
suggest blood loss.
Patients presenting with chronic anemias often
complain of fatigue and weakness. Other voiced
November 2013 • www.ebmedicine.net

Diagnostic Studies
As mentioned earlier, anemia is defined as an absolute decrease in the number of circulating RBCs, and
it is a laboratory diagnosis based on an abnormally
low value of hemoglobin, hematocrit, or RBC count.
The hemoglobin measures the concentration of the
major oxygen-carrying pigment in whole blood. The
hematocrit is the percentage of a sample of whole
blood that is occupied by intact RBCs. The RBC
count is the number of RBCs contained in a specified
volume of whole blood. Some institutions have theability to determine the hematocrit at the bedside (ie,spun hematocrit). This can be useful for establishing the diagnosis of anemia but is not helpful in theevaluation of anemia. The evaluation of anemia generally follows one of two approaches: (1) the kinetic
approach, which is based on the mechanism of theanemia; or (2) the morphological approach, which isbased on RBC indices.
The more commonly used method of evaluation is the morphological approach. The RBC indicesthat are typically used are the MCV, MCH, MCHC,
7Emergency Medicine Practice © 2013

Clinical Pathway For The Evaluation Of Anemia

Hemoglobin < 12 g/dL

MCV < 81 fL

•
•
•
•
•
•
•
•

Peripheral blood smear:microcytic or hypochromic RBCs?

NO

Acute blood loss
Chronic disease
Chronic renal insufficiency
Hypothyroidism
Bone marrow suppression
Hemolysis
G-6-PD deficiency
Aplastic anemia

iron, ­ TIBC,
ferritin

•
•
•
•
•
•
•

Vitamin B12 deficiency
Folate deficiency
Liver disease
Reticulocytosis
Myelodysplastic syndromes
ETOH abuse
Drugs (hydroxyurea, AZT, chemotherapeutic agents)

Peripheral blood smear:schistocytes, helmet cells,
spherocytes, bite cells?

Peripheral blood smear:large oval-shaped RBCs,
hypersegmented neutrophils?

YES

NO

• Iron deficiency• Thalassemia• Sideroblastic
anemia• Chronic disease (late)➞ ➞Lead intoxication

YES

➞

NO

MCV > 100 fL• Acute bloodloss• Chronic
disease• Chronic renal
insufficiency• Hypothyroidism• Bone marrow
suppression• Aplastic
anemia­LDH,
globinNO➞

Iron deficiency
Thalassemia
Sideroblastic anemia
Lead intoxication
Chronic disease (late)

➞

•
•
•
•
•

MCV 81-100 fL

hapto-

Hemolysis

YES• Liver disease• Reticulocytosis• Myelodysplastic syndromes• ETOH abuse• Drugs

Iron deficiency

Nonautoimmune hemolytic
anemia• Vitamin B12
deficiency• Folate
deficiency

ObtainVitamin B12 andfolate levels

Coombs test
NEGATIVE• Thalassemia• Sideroblastic
anemia• Chronic disease (late)

YES

POSITIVE

Autoimmune
hemolytic anemia

Abbreviations: AZT, zidovudine; ETOH, ethanol; G-6-PD, glucose-6-phosphate dehydrogenase; Hgb, hemoglobin; LDH, lactate dehydrogenase; MCV,
mean corpuscular value; RBC, red blood cell; TIBC, total iron-binding capacity.

Emergency Medicine Practice © 20138www.ebmedicine.net • November 2013

and RDW. The MCV is calculated from the following formula: hematocrit x 10/RBC count. The MCV
can be artificially elevated in the presence of cold
agglutinins. The MCH is derived from the following
formula: hemoglobin x 10/RBC count. Iron deficiency and thalassemias are the most common causes
for a reduced MCH, and an elevated MCH denotes
a macrocytosis of any cause. The MCHC is calculated by the following formula: hemoglobin x 100/
hematocrit. Reductions in the MCHC are caused by
the same conditions that will reduce the MCV and
MCH. An elevated MCHC is almost always causedby the presence of spherocytosis or congenital hemolytic anemias (eg, sickle cell anemia).
The RDW is the least commonly used RBC index
and represents a measure of the degree of variationin RBC size. The RDW is calculated from the following formula: standard deviation of MCV/MCV
x 100. Elevated values indicate the presence of cells
that differ in size. Although an abnormal RDW is
not diagnostic for any particular disorder, elevatedvalues indicate a need for a microscopic review of amanual peripheral blood smear.
With the current technology, all of the RBC
indices are automated and derived at the sametime the hemoglobin, hematocrit, and RBC countare measured. The evaluation of anemia is usuallybased on obtaining a complete blood count (CBC).
Although the anemia is based on the RBC component of the CBC, the presence of abnormalities in
the white blood cell count or platelet count may
suggest causes for the anemia (eg, aplastic anemia,
thrombotic thrombocytopenic purpura, or chronic
lymphocytic leukemia).6,10
Additional laboratory studies may be indicatedonce the initial CBC and RBC indices are evaluated.
(See the Clinical Pathway, page 8.) Some machinesthat measure the CBC will also report an automatedevaluation of the peripheral blood smear. A peripheral blood smear is most useful in the evaluationof a hemolytic anemia, an anemia associated withthrombocytopenia, or white blood cell disorders. In
these settings, a manual peripheral blood smear isindicated, which is more reliable than the automatedform. In the presence of pancytopenia, a reticulocyte
count should be considered. The reticulocyte countreflects the activity of the bone marrow. A decreased
value in the setting of pancytopenia strongly suggests aplastic anemia. Iron studies, as well as otherblood work, may be indicated but are not part of theinitial evaluation of anemia.
Once anemia is diagnosed, the RBC indicesshould be evaluated, particularly the MCV. If the
MCV is decreased (microcytic anemia), then serum
iron, total iron-binding capacity, and ferritin values
should be ordered. An elevated MCV is an indication for obtaining folate and vitamin B12 levels. In
most ED settings, the results of these specialized
November 2013 • www.ebmedicine.net

blood tests will not be available while the patientis still in the ED. However, these data can be very
useful to the healthcare provider that will be assuming care of the patient after the ED visit. An anemia
with a normal MCV (particularly if hemolysis isconsidered) should prompt the ordering of a manual
peripheral blood smear. The presence of schistocytes
and helmet cells are often seen in microangiopathic(intravascular) hemolytic anemia. Spherocytes andelliptocytes are often seen in autoimmune hemolytic
conditions, hereditary spherocytosis, and extravascular hemolysis. The peripheral blood smear
associated with sickle cell disease (one of the mostcommon extravascular hemolytic anemias) typicallydemonstrates sickle cells and target cells. A haptoglobin, LDH, and Coombs test should also be obtained if hemolysis is suggested. A positive Coombs
tests is very suggestive of an autoimmune hemolytic
anemia and will alter therapy.6,10

Treatment
As with any medical condition, assuring adequate
oxygenation, ventilation, and hemodynamic stability are the primary priorities. Once the diagnosis ofanemia is established, the next hurdle to overcome
is to determine whether the anemia requires specifictreatment, especially RBC transfusion. The universally accepted trigger for transfusion is based on
the presence of clinical symptoms or signs that are
determined to be caused by the anemia.
In an asymptomatic anemic patient, the need totransfuse is less clear and the literature is conflicting. In the past, the decision to transfuse RBCs wasoften based on the “10/30 rule,” utilizing a threshold of hemoglobin of 10 g/dL or a hematocrit of 30%
for transfusion.22 In favor of a specific threshold totransfuse is the fact that anemia is associated withworse outcomes in some patients.23,24 In a retrospective cohort study of 2083 patients, individuals withpostoperative hemoglobin of 7.1 to 8 g/dL had 0%
mortality and 9.4% morbidity, while patients withhemoglobin of 4.1 to 5 g/dL had 34.4% mortality
and 57.7% morbidity.25 However, arguing against
transfusions based solely on a specific threshold aredata from patients who refuse transfusion (usuallyfor religious reasons). These patients can have similar or better outcomes than their transfused counterparts, despite having low hemoglobin values.26,27
A 2009 retrospective cohort study, however, demonstrated that 1958 Jehovah’s Witness patients had a
33.3% mortality rate when postoperative hemoglobin was ≤ 6 g/dL, which demonstrates that very low
hemoglobin values (defined as a hemoglobin ≤ 6 g/dL) are not well tolerated.28
Transfusion of RBCs has its own set of problems. Besides the potential problems of transfusion
reactions, infection, volume overload, iron overload
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and transfusion-related acute lung injury, criticallyill patients receiving RBC transfusions have worse
outcomes.29-31 In a recent study of 167 critically illpatients, transfusion was shown to be an independentrisk factor for mortality, with an odds ratio (OR) of
2.67. In addition, transfused patients in this study had
longer intensive care unit (ICU) and hospital stays.32
The optimal level of hemoglobin to trigger RBC
transfusions in asymptomatic anemic patients is
unknown.32 Recent studies have attempted to better
define indications for RBC transfusions. A Cochranereview of 6264 patients showed that a restrictive
transfusion strategy (defined as a hemoglobin of
7-8 g/dL) was associated with a reduction in risk ofreceiving a RBC transfusion by 39%. The use of therestrictive strategy did not impact the rate of adverse
events compared to a liberal transfusion strategy(defined as a threshold hemoglobin of 9.5-10 g/dL), and it was associated with a significant reduction in hospital mortality (relative risk of 0.77) but
not a reduction in 30-day mortality.33 The results ofthis Cochrane review are consistent with publishedclinical practice guidelines, which recommend using
lower hemoglobin values (6-8 g/dL) as the thresholdfor RBC transfusion.34-36 At this time, data are insufficient to use a threshold < 6 g/dL.37
Trauma and upper gastrointestinal hemorrhage
are the most common indications for RBC transfusion in acute anemia.38 A 2010 Cochrane review was
unable to demonstrate a benefit from RBC transfusion in patients with acute upper gastrointestinal
bleeding; however, the authors noted that the evidence at the time was suboptimal.39 A recent study
randomized 921 patients presenting with acute
upper gastrointestinal bleeding to a restrictive transfusion strategy (hemoglobin < 7 g/dL) and a liberaltransfusion strategy (hemoglobin < 9 g/dL). The
45-day mortality was 5% in the restrictive group and
9% in the liberal group (P = .02). The risk of rebleeding was also lower in the restrictive group (10%)
compared to the liberal group (16%) (P = .01).40 This
study supports additional data from patients withacute bleeding that have shown that RBC transfusions increase the risk of rebleeding.41 European
guidelines for RBC transfusion for acute anemia
recommend even lower thresholds (eg, hemoglobin< 6.4 g/dL in healthy adults aged < 60 years).42
Each unit of transfused packed RBCs in patients
who are not actively bleeding increases the hemoglobin approximately 1 g/dL.43 In a prospective studyof 52 patients who were not bleeding, it was determined that post-transfusion hemoglobin levels canbe reliably determined as little as 15 minutes after thetransfusion is complete, and waiting a longer time toassess the effects of RBC transfusion is not required.44
The need to treat anemia in the setting of acutecoronary syndromes is less clear. A retrospective
study of 3324 elderly patients with acute myocardial
Emergency Medicine Practice © 2013

infarction showed that RBC transfusion for hematocrit
between 5% and 24% was associated with a reduction in 30-day mortality, (adjusted OR, 0.22).45 In acohort study of 39,922 patients, anemia was found in
30.6% of patients, but hemoglobin < 10 g/dL was seen
in only 5.4% of patients. In this study, patients with
ST-elevation myocardial infarction and a hemoglobin< 14 g/dL had higher mortality and recurrent cardiovascular events, with an adjusted OR of 1.21 (P < .001).
Similarly, patients with non-ST-elevation myocardial
infarction had high mortality and recurrent cardiovascular events with hemoglobin < 11 g/dL (OR, 1.31;
P = .027).46 In this same study, the rate of cardiovascular events and death increased with hemoglobin
levels > 16 g/dL. However, a recent meta-analysis
revealed an increase in all-cause mortality associatedwith RBC transfusions in patients with acute coronary
syndromes compared to no transfusions: 18% versus
10.2%, respectively (P < .001). In this same study, asubgroup analysis showed that RBC transfusions may
be of benefit in patients with hematocrit < 30%; however, the data were not strong enough to show statisticalsignificance.47 The practical application of this study islimited because the analysis was not stratified by baseline hemoglobin values. Since low hemoglobin levels
are associated with worse outcomes in acute coronary
syndromes and use of RBC transfusions may also be
associated with worse outcomes, confusion remains
as to which patients benefit, based on hemoglobin
thresholds. Neither the American Heart Association
nor the European Society of Cardiology specify a hemoglobin trigger to use in the setting of acute coronary
syndromes.48,49 Until better data are available, utilizinga hemoglobin < 9 to 10 g/dL to trigger the replacementof RBCs in this population seems prudent.
Autoimmune hemolytic anemia presents with
its own particular issues. The treatment of choicefor these patients is corticosteroids: 1 to 1.5 mg/kg
of prednisone or its equivalent. However, improvement in the anemia associated with steroid therapy
can take up to 1 to 3 weeks.50 The threshold for RBC
transfusion in these patients is even more confusing,since the use of incompatible blood can worsen thehemolytic process. Steroid therapy should be initiated in the ED; however, the use of RBC transfusion
is best done in consultation with a hematologist. Despite these issues, a patient with acute autoimmune
hemolytic anemia who has severe hemolysis should
be approached the same as any patient with a lifethreatening anemia, including the use of unmatched
RBC transfusions, if indicated.
In the absence of a confirmed diagnosis for a
specific form of anemia, the empiric use of iron, folate, and vitamin B12 supplements in the ED setting
should be avoided. The use of nutritional supplements may delay the actual cause and workup of theanemia by assuming that the supplementation will
remedy the problem.
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Special Circumstances

Disposition

The evaluation and treatment of anemia are thesame for all age groups and patient populations.
Certain forms of anemia (eg, sickle cell anemia)
require specific therapies and transfusion thresholds
that are beyond the scope of this article. Iron-deficiency anemia is the most common form of anemia
in pregnancy.51 A recent systematic review suggested benefit from oral iron replacement,51 but there
are no data supporting RBC transfusions for chronic
anemia in this patient group.
The data supporting RBC transfusions for thetreatment of anemia are less robust in children thanin adults. However, the literature currently available
shows similar thresholds and results as those usedin adults. The TRIPICU study was a prospective randomized controlled trial of 648 critically ill childrenthat compared a restrictive hemoglobin threshold fortransfusion of 7 g/dL to a liberal threshold of 9.5 g/
dL. There was no significant difference in morbidity
or 28-day mortality between the 2 groups.52 Anotherprospective randomized controlled study of 137
children with sepsis compared outcomes of transfusing for a hemoglobin < 7 g/dL to a hemoglobin < 9.5
g/dL. No clinically significant difference was noted
in morbidity or ICU mortality.53 A more recent
systematic review concluded that patients with a hemoglobin > 7 g/dL do not have an outcome benefit
from transfusions and suggested an increased risk ofmorbidity and mortality with transfusions.54

Disposition of the patient with anemia is dependent
on several factors. The patient who has symptoms
related to anemia is likely to require admission to
the hospital. In most cases, acute anemia will require
admission, usually to an intensive care or acute careunit. The exception may be a case where the blood
loss is known and well controlled (eg, a major laceration that has been repaired). A patient with acuteanemia who is discharged needs explicit instructions
on when to return or seek medical assistance. The
vast majority of patients who require RBC transfusion will not be discharged from the ED unless thepatient has been receiving chronic transfusions on an
outpatient basis. Patients with asymptomatic stablechronic anemia can usually be safely discharged.10 A
stable, but new, anemia that is diagnosed in the ED
should have follow-up arranged prior to discharge.
Although specific laboratory tests that are indicatedin the evaluation of anemia can be ordered in theED, studies with delayed turnaround times can befollowed up by the patient’s physician or consultant.

Summary
Anemia is a common occurrence in all age groups.
The initial focus of the emergency clinician evaluating anemia should be on determining whether theanemia is acute or chronic. Acute anemia is mostcommonly associated with blood loss, and chronic
anemia is usually clinically stable. The clinicalpresentation of anemia is nonspecific and morecommonly seen with acute anemia. The presence ofjaundice or scleral icterus should alert the physician
to the possibility of a hemolytic anemia.
The diagnosis of anemia is based on laboratory
findings, and the evaluation for anemia should bebased on a systematic approach. Iron deficiency
is the most common cause of microcytic anemia,
and if it is suspected, order serum iron, total ironbinding capacity, and ferritin levels. Suspicion ofmacrocytic anemia should prompt the ordering offolate and vitamin B12 levels. The results of studies
ordered in the workup of microcytic or macrocytic
anemias may not be available by the time disposition from the ED is being considered. A normocytic anemia or an elevated RDW should prompt
the ordering of a peripheral blood smear, and theresults can then be used to guide the ordering ofadditional laboratory studies.
The major dilemma associated with the evaluation of anemia is when to replace RBCs. The old“10/30 rule” should be avoided, since it is notsupported in the literature. Patients can toleratevery low hemoglobin levels in chronic anemia;
however, the literature shows that hemoglobin
levels < 6 g/dL (especially in acute anemia) are

Controversies And Cutting Edge
The universally accepted indication for emergent
RBC transfusion is hemorrhagic shock.36-38 The decision to transfuse RBCs during the initial resuscitation in hemorrhagic shock is based on the clinicalcondition of the patient, the evidence of the amountof blood lost, and the potential for ongoing bleeding. The American College of Surgeons’ Advanced
Trauma Life Support (ATLS) course recommends
considering RBC transfusions after administering
2 20-mL/kg fluid boluses of crystalloid solution inpatients with ongoing hemorrhagic shock.55 Despite
the accepted principles of the ATLS course andthe common-sense concept of blood transfusion insevere hemorrhage, there are little scientific data
defining the goals for the use of RBC transfusions
in the resuscitation of hemorrhagic shock.35 The indications for emergency-release or uncrossmatchedblood is even less well defined in the literature;
however, the use of this type of RBC transfusion appears to be relatively safe.56,57 For more informationon the management of traumatic hemorrhagic shock,see the November 2011 issue of Emergency Medicine
Practice, "Traumatic Hemorrhagic Shock: Advances
In Fluid Management (Trauma CME)."
November 2013 • www.ebmedicine.net

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Risk Management Pitfalls For The Patient With Anemia
1.

“He didn’t say he was on warfarin, so why
would I check an INR?”
Many elderly patients are poor historians
secondary to dementia or polypharmacy. In anelderly patient being evaluated for anemia, theINR should be considered, as elderly patientsare more likely to omit mentioning prescribed
medications than their younger counterparts
and are more likely to develop coagulopathies
from other causes.

2.

“Patients always exaggerate how much bleeding there is. Most is self-limited anyway.”
Bleeding (eg, from the gastrointestinal tract andupper airway) can produce a significant amountof hemorrhage that may require admission to
the hospital for observation.

3.

“The patient with a gastrointestinal bleed wasold, but he didn’t have any chest pain, so why
would I get an ECG?”
Many older patients have major cardiovascularrisk factors. With enough bleeding, there may
be ECG changes to suggest cardiac ischemia
secondary to supply/demand mismatch.

4.

“The hemoglobin was 9 g/dL, so I didn’t think
she needed a transfusion; I just gave her 1.5 L
of normal saline for resuscitation.”
By initiating too much crystalloid, there is
the possibility of dilution of RBCs, causing
decreased oxygen-carrying capacity and further
injury (such as cardiac ischemia).

5.

“The patient came in with a history of moderate gastrointestinal bleeding and a bloodpressure of 90/60 mm Hg. I gave him 2 L of
crystalloid. The blood pressure improved, but
the bleeding restarted.”
While not true for every patient, it may be moreadvantageous to allow a patient to be mildly
hypotensive as long as they do not show signsof tissue hypoperfusion. Increasing the bloodpressure may disrupt primary hemostasis ashydrostatic forces within the blood vessels
increase.

Emergency Medicine Practice © 2013

6.

“The vital signs are normal, so he can’t be
bleeding much.”Many patients are on beta blockers or otheratrioventricular nodal blocking agents that may
falsely normalize the vital signs in the face ofsignificant hemodynamic compromise.

7.

“I gave the patient 4 units of packed RBCs, but
she continued to bleed and deteriorate.”
When patients bleed, they lose more than justRBCs. Coagulation factors and platelets are also
lost as hemorrhage continues, and dilutional
coagulopathies can occur. Resuscitation withfresh frozen plasma (and possibly platelets)
may be required, depending on the degreeof bleeding and amount of RBCs that aretransfused.

8.

“Since the patient’s hemoglobin was 11 g/dL
with a low MCV of 78 fL, I figured the anemia
was due to iron deficiency and I discharged
him on iron supplements.”
Although iron deficiency is the most common
cause of a microcytic anemia, other causes of alow MCV need to be considered. As it turned
out, this patient had thalassemia minor, which
is usually asymptomatic and does not require
treatment.

9.

“The hemoglobin was 9.8 g/dL; since it was< 10 g/dL, I transfused the patient.”
No isolated threshold hemoglobin value has
been shown to correlate with outcome of RBC
transfusion. The use of blood transfusions
should be based on whether the patient has
clinical symptoms or signs suggesting aclinically significant anemia and not on as
specific number.

10. “The parents said there was blood in theirbaby's diaper, so I felt I needed to work up apotential coagulopathy and anemia.”
In infants with a history of rectal bleeding, thefirst step is to confirm that what the parents saw
was really blood. Even if blood is not confirmedon the rectal examination, a laboratory screening
for anemia and coagulopathy should be
pursued.

12

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associated with worse outcomes compared tohemoglobin levels above this value. On the other
hand, the literature has also shown that the useof transfusions is associated with poor outcomes.
The unanswered question is, “At what pointshould a patient receive RBC replacement?” Current literature and clinical guidelines show thatusing a restrictive transfusion strategy (defined asa transfusion hemoglobin threshold < 6-8 g/dL) is
associated with better outcomes than using a liberal strategy (hemoglobin < 9-10 g/dL). However,
the hemoglobin level that should be the endpointof transfusion therapy is still not known. A safe
approach would seem to be to transfuse RBCs inasymptomatic anemia when the hemoglobin is< 6 to 8 g/dL but to limit transfusions once thehemoglobin is no more than 9 to 10 g/dL.
Disposition of the anemic patient is morestraightforward. Patients with acute anemia andthose requiring RBC transfusions are likely to needadmission to the hospital. Patients with stable chronic anemia can usually be safely discharged from theED, even if the laboratory workup is not complete.
Unless it is an unusual circumstance, follow-up
should be provided at the time of discharge.

IU/L and the haptoglobin was reduced at 15 mg/dL. The
Coombs test was positive, which confirmed the diagnosisof an acute autoimmune hemolytic anemia. Because RBC
transfusion was anticipated but the patient had an acuteautoimmune hemolytic anemia, you consulted hematology. Prednisone (1.5 mg/kg) was given and transfusion
was also recommended with a goal of hemoglobin > 7 to
8 g/dL. The hematologist noted that there would likely beconsiderable delay in crossmatching blood for the patient.
He recommended monitoring the hemoglobin and hematocrit every 3 to 4 hours, and if the patient became moreanemic prior to receiving crossmatched blood, type-specific uncrossmatched blood should be transfused. The patient
was admitted to the ICU in a stable condition, with a final
diagnosis of acute autoimmune hemolytic anemia, likely
caused by the ibuprofen.
In case 2, the patient was on dabigatran, so the administration of aspirin was not warranted and may haveeven been detrimental because of the concerns for gastrointestinal bleeding. In this case, his cardiac supply-demand mismatch was secondary to his acute blood loss andunlikely secondary to underlying coronary artery disease(though a contributing factor). Therefore, cardiac catheterization was not likely to benefit this patient. Correctionof the patient’s anemia would likely reverse the myocardial ischemia. The patient was transfused with 2 units ofcrossmatched packed RBCs. You did not give fresh frozen
plasma or prothrombin complex concentrate because his
coagulation studies were normal and he was not actively
hemorrhaging. A repeat ECG showed normalization of the
ST segments, and his symptoms dissipated. Both cardiology and gastroenterology were consulted, and the patient
was admitted to the ICU. The final diagnosis was gastrointestinal bleeding from a gastric ulcer and myocardialischemia secondary to supply-demand mismatch.
The child in the third case appeared to be in significant high-output heart failure. You treated him with supplemental oxygen and a 1 mg/kg dose of furosemide. You
considered noninvasive positive pressure ventilation, but
an appropriate face mask was not available for this verysmall patient. The scleral icterus and hepatosplenomegalysuggested a possible hemolytic anemia. In this case,further studies were warranted, including liver function
tests, LDH, a blood smear, and a type and screen. The
blood smear showed microcytic RBCs, tear drop cells, andtarget cells. An elevated LDH and decreased haptoglobin
confirmed a hemolytic process. Liver function studies
showed an abnormally high unconjugated bilirubin that
correlated with his jaundice. Because of the hemolytic
process and a microcytic anemia, you consulted hematology and ordered a hemoglobin electrophoresis. Based on
the hematologic data, the hematologist suspected a thalassemia and recommended RBC transfusions to a hemoglobin of 9 to 10 g/dL and asked that the child be admitted
to the ICU. Ultimately, this patient was found to havebeta-thalassemia major and required additional transfusions and chelation therapy to reduce iron burden.

Case Conclusions
In case 1, the RBC indices were normal (MCV = 86.7 fL,
MCH = 27.3 pg, MCHC = 34.5%); however, the RDW
was increased at 23.9%. Because the patient had scleralicterus and the RDW was elevated, a peripheral bloodsmear was ordered, which showed spherocytes. Based on
the peripheral blood smear results, you were concerned
for a hemolytic anemia and ordered LDH, haptoglobin
levels, and a Coombs test. The LDH was elevated at 717

Time- And Cost-Effective
Strategies
•
•
•
•
•
•

A systematic approach to the evaluation of anemia can often determine the cause and limit theordering of unneeded laboratory studies.
The need for RBC transfusion should be basedon clinical signs and symptoms and not on a
specific hemoglobin level.
The effectiveness of RBC transfusion can be determined within 15 minutes after administration(as opposed to hours).
In the absence of a definitive diagnosis, prescribing iron, folate, or vitamin B12 supplementationin the ED should be avoided.
Consider restricting transfusions to patients witha hemoglobin < 6 to 8 g/dL.
Consider a restrictive transfusion approach inpatients with a gastrointestinal bleed.

November 2013 • www.ebmedicine.net

13

Emergency Medicine Practice © 2013

References

18.

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references areequally robust. The findings of a large, prospective,
random­ized, and blinded trial should carry moreweight than a case report.
To help the reader judge the strength of eachreference, pertinent information about the study
will be included in bold type following the ref­erence, where available.
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2010;95(11):1849-1856. (Prospective population-based observational study)
Kristinsson G, Shtivelman S, Hom J, et al. Prevalence ofoccult anemia in an urban pediatric emergency department;
what is our response? Pediatr Emerg Care. 2012;28(4):313-315.
(Retrospective observational study)
Pitetti RD, Lovallo A, Hickey R. Prevalence of anemia inchildren presenting with apparent life-threatening events.
Acad Emerg Med. 2005;12(10):926-931. (Prospective cohort
study)
Matteson KA, Raker CA, Pinto SB, et al. Women presenting
to an emergency facility with abnormal bleeding: patientcharacteristics and prevalence of anemia. J Reprod Med.
2012;57(1-2):17-25. (Retrospective cohort study)
Kaushansky K, Beutler E, Lichtman MA, et al, eds. Williams
Hematology. 8th ed. New York: McGraw Hill Medical; 2011.
Gage BF, Fihn SD, White RH. Warfarin therapy for an
octogenarian who has atrial fibrillation. Ann Intern Med.
2001;134(6):465-474. (Case-based review)
Anderson FA, Wheeler HB, Goldberg RJ, et al. A populationbased perspective of the hospital incidence and case-fatality
rates of deep vein thrombosis and pulmonary embolism. The
Worcester DVT Study. Ann Inter Med. 1991;151(5):933-938.
(Population-based perspective observational study)
Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic
complications of anticoagulant treatment. Chest. 2001;119(1suppl):108S-121S. (Review)
Janz TG, Hamilton GC. Anemia, polycythemia, and whiteblood cell disorders. In: Marx JA, Hockberger RS, Walls RM,
et al, eds. Rosen’s Emergency Medicine Concepts and Clinical
Practice. 7th ed. Philadelphia, PA: Mosby Elsevier; 2010.
Borgna-Pignatti C. Modern treatment of thalassemia intermedia. Br J Haematol. 2007;138:291-299. (Review)
Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med.
2005;353:1135-1139. (Review)
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl
J Med. 2005;352-357. (Review)
Packman CH. Hemolytic anemia due to warm autoantibodies. Blood Rev. 2008. 22(1):17-31. (Review)
Glassberg J. Evidence based management of sickle celldisease in the emergency department. Emerg Med Pract. 2011;13(8):1-20. (Review)
Kehat I, Shupak A, Goldenberg I, et al. Long-term hematological effects in Special Forces trainees. Mil Med.
2003;168:116-119. (Retrospective observational study)
Synder SR, Kivlehan SM, Collopy KT. Prehospital management of the anemia patient: what you need to know about
this common blood disorder and its clinical manifestations.

Emergency Medicine Practice © 2013

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EMS World. 2011;40(9):65-72. (Review)
Tefferi A. Anemia in adults: a contemporary approach todiagnosis. Mayo Clin Proc. 2003;78(10):1274-1280. (Review)
Nardone DA, Roth KM, Mazur DJ, et al. Usefulness of physical examination in detecting the presence of anemia. Arch
Intern Med. 1990;150(1):201-204. (Prospective observational
study)
Hung OL, Kwon NS, Cole AE, et al. Evaluation of the physician’s ability to recognize the presence or absence of anemia,
fever, and jaundice. Acad Emerg Med. 2000;7(2):146-156.
(Prospective observational study)
Sheth TN, Choudry NK, Bowes M, et al. The relation of conjunctival pallor to the presence of anemia. J Gen Intern Med.
1997;12(2):102-106. (Prospective observational study)
Wang JK, Klein HG. RBC transfusion in the treatment andmanagement of anaemia: the search for the elusive transfusion trigger. Vox Sang. 2010;98(1):2-11. (Review)
Hare GM, Freedman J, David Maser C. Review article: risksof anemia and related management strategies: can perioperative blood management improve patient safety? Can J
Anaesth. 2013; 60(2):168-175. (Review)
Karkouti K, Wijeysundera DN, McCluskey SA, et al. The
influence of baseline hemoglobin concentration on toleranceof anemia in cardiac surgery. Transfusion. 2008;48(4):666-672.
(Retrospective observational study)
Carson JL, Noveck H, Berlin JA, et al. Mortality and morbidity in patients with very low postoperative Hb levels who
decline blood transfusion. Transfusion 2002; 42(7):812-818.
(Retrospective cohort study)
Pattakos G, Koch CG, Brizzio ME, et al. Outcome of patients
who refuse transfusion after cardiac surgery. Arch Intern Med
2012;172(15):1154-1160. (Prospective cohort study)
Vaziri K, Roland JC, Robinson LL, et al. Extreme anemia in
an injured Jehovah’s Witness: a test of our understanding of
the physiology of severe anemia and the threshold for bloodtransfusion. J Trauma. 2009;67(1):E11-E13. (Case report)
Tobian AA, Ness PM, Noveck H, et al. Time course andetiology of death in patients with severe anemia. Transfusion.
2009;49(7):1395-1399. (Retrospective cohort study)
Marik PE, Corwin HL. Efficacy of red blood cell transfusionin the critically ill: a systematic review of the literature. Crit
Care Med. 2008:36(9):2667-2674. (Systematic review)
Fuller BM, Gajera M, Schorr C, et al. The impact of packed
red blood cell transfusion on clinical outcomes in patientswith septic shock treated with early goal directed therapy.
Indian J Crit Care Med. 2010;14(4):165-169. (Retrospective
cohort study)
Weiskopf RB. Do we know when to transfuse red cells to treat
acute anemia? Transfusion. 1998;38(6):517-521. (Editorial)
Silva Junior JM, Rezende E, Amendola CP, et al. Red blood
cell transfusions worsen the outcomes even in critically illpatients undergoing a restrictive transfusion strategy. Sao
Paulo Med J. 2012;130(2):77-83. (Prospective cohort study)
Carson JL, Carless PA, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood
cell transfusion. Cochrane Database Syst Rev. 2012 Apr
18;4:CD002042. (Systematic review)
Carson JL, Grossman BJ, Kleinman S, et al. Red blood celltransfusion: a clinical practice guideline from the AABB. Ann
Intern Med. 2012;157(1):49-58. (Practice guidelines)
Napolitano LM, Kurek S, Luchette FA, et al. Clinical practiceguideline: red blood cell transfusion in adult trauma andcritical care. Crit Care Med. 2009;37(12):3124-3157. (Practiceguidelines)
American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practiceguidelines for perioperative blood transfusion and adjuvant
therapies: an updated report by the American Society ofAnesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiol. 2006;105(1):198-

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Carson JL, Carless PA, Hebert PC. Outcomes using lower vshigher hemoglobin thresholds for red blood cell transfusion.
JAMA. 2013;309(1):83-84. (Clinical evidence synopsis)
Beckwith H, Manson L, McFarlane C, et al. A review ofblood product usage in a large emergency department over a
one-year period. Emerg Med J. 2010;227(6):439-442. (Retrospective case series)
Jairath V, Hearnshaw S, Brunskill SJ, et al. Red cell transfusion for the management of upper gastrointestinal haemorrhage. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD006613.
(Systematic review)
Villanueva C, Colomo A, Bosch A, et al. Transfusion
strategies for acute gastrointestinal bleeding. N Engl J Med.
2013;368(1):11-21. (Randomized control study)
Restellini S, Kherad O, Jairath V, et al. Red blood cell transfusion is associated with increased rebleeding in patientswith nonvariceal upper gastrointestinal bleeding. Aliment
Pharmacol Ther. 2013;37(3):316-322. (Prospective observational study)
Dutch Institute for Healthcare Improvement. Transfusion
policy for acute anemia. In: Blood transfusion guideline.
Utrecht (The Netherlands). 2011:166-208. (Practice guidelines)
Lee JH, Kim DH, Kim K, et al. Predicting change of hemoglobin after transfusion in hemodynamically stable anemic
patients in emergency department. J Trauma. 2010;68(2):337341. (Retrospective observational study)
Wiesen AR, Hospenthal DR, Byrd JC, et al. Equilibration ofhemoglobin concentration after transfusion in medical inpatients not actively bleeding. Ann Intern Med. 1994;121(4):278280. (Prospective observational study)
Wu WC, Rathore SS, Wang Y, et al. Blood transfusion inelderly patients with acute myocardial infarction. N Engl J
Med. 2001;345(17):1230-1236. (Retrospective cohort study)
Sabatine MS, Morrow DA, Giugliano RP, et al. Association ofhemoglobin levels with clinical outcomes in acute coronary
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cohort study)
Chatterjee S, Wettersley J, Sharma A, et al. Association ofblood transfusion with increased mortality in myocardial
infarction. JAMA Intern Med. 2013;173(2):132-139. (Metaanalysis)
Wright RS, Anderson JL, Adams CD, et al. 2011 ACC/AHA
focused update of the guidelines for the management ofpatients with unstable angina/non-ST-elevation myocardial infarction updating the 2007 guidelines. Circulation.
2011;123(18):2022-2060. (Practice guidelines)
Bassand JP, Hamm CW, Ardissino D, et al. Guidelines forthe diagnosis and treatment of non-ST-segment elevation
acute coronary syndromes: The Task Force for the Diagnosis
and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur
Heart J. 2007;28(13):1598-1660. (Practice guidelines)
Reardon JE, Marques MB. Laboratory evaluation and transfusion support of patients with autoimmune hemolytic anemia. Am J Clin Pathol. 2006;125(Suppl 1):S71-S77. (Review)
Reveiz L, Gyte GM, Cuervo LG, et al. Treatments of irondeficiency anaemia in pregnancy. Cochrane Database Syst Rev.
2011 Oct 6;(10):CD003094. (Systematic review)
Rouette J, Trottier H, Ducruet T, et al. Red blood cell transfusion threshold in postsurgical pediatric intensive care patients: a randomized clinical trial. Ann Surg. 2010;251(3):421427. (Randomized controlled trial)
Karam O, Tucci M, Ducruet T, et al. Red blood cell transfusion thresholds in pediatric patients with sepsis. Pediatr
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Tyrrell CT, Bateman ST. Critically ill children: to transfuse
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Life Support Manual. 8th ed. Chicago: American College ofSurgeons; 2008.
Saverimuttu J, Greenfield T, Rotenko I, et al. Implications forurgent transfusion of uncrossmatched blood in the emergency department: the prevalence of clinically significant red
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2003;15(3):239-243. (Retrospective observational study)
Mulay SB, Jaben EA, Johnson P, et al. Risks and adverse
outcomes associated with emergency-release red blood celltransfusion. Transfusion. 2013;53(7):1416-1420. (Retrospective
observational study)

CME Questions
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15

1.

A “restrictive” transfusion strategy:
a. Employs a hemoglobin threshold of < 9 to
10 g/dLb. Employs a hemoglobin threshold of < 6 to
8 g/dLc. Is associated with worse outcomesd. Is the same as the 10/30 rule2.

Anemia of blood loss is characterized by anormal hemoglobin value with abnormal RBC
indices.
a. Trueb. False

3.

Which of the following laboratory tests would
help to differentiate between decreased RBC
production and increased RBC destruction?
a. MCVb. Reticulocyte countc. Absolute hemoglobin difference
d. RDW

Emergency Medicine Practice © 2013

4.

What constellation of physical examination
findings would you expect in a patient withextravascular hemolysis?
a. Scleral icterus, brown/red urine, 		splenomegalyb. Scleral icterus, normal or orange urine, 		splenomegalyc. Normal sclera, dark urine, no splenomegaly
d. Normal sclera, normal urine, no 		
splenomegaly

5.

In which of the following conditions would
you least expect to find schistocytes on peripheral blood smear?
a. Mechanical prosthetic valveb. Thrombotic thrombocytopenic purpurac. Disseminated intravascular coagulationd. Sickle cell disease6.

The most common cause of clinically significant anemia is:
a. Thalassemiab. Blood lossc. Liver diseased. Marathon running7.

All factors being equal, which of the following
hemoglobin levels would you not transfuse?
a. 4.5 g/dL
b. 5.5 g/dL
c. 10 g/dL
d. 6.9 g/dL

8.

How much would you expect the hemoglobin
to rise in a patient after being given 1 unit ofpacked RBCs?
a. 1 g/dL
b. 2 g/dL
c. 3 g/dL
d. 4 g/dL

Physician CME Information
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