Approach Considerations

To evaluate anemia, obtain initial laboratory tests, including the complete blood count (CBC),
reticulocyte count, and review of the peripheral smear. (See the diagram below.)

An overwhelming majority of acute anemia is normocytic, although marked reticulocytosis may

raise mean corpuscular volume (MCV). If microcytic, it has an underlying chronic anemia
component, and one needs to know the cause.

Algorithm for diagnostic approach

and workup of anemia in children. Hb=hemoglobin; Hct=hematocrit; HS=hereditary spherocytosis;
HE=hereditary elliptocytosis; G-6-PD=glucose-6-phosphate dehydrogenase; PK=pyruvate kinase;
HUS=hemolytic uremic syndrome; TTP=thrombotic thrombocytopenic purpura; DIC=disseminated
intravascular coagulation; DBA=Diamond-Blackfan anemia.
Chest radiography is performed in patients who may have CHF and to rule out mediastinal mass
(associated with acute leukemia).

Abdominal ultrasonography is used to assess for gallstones or splenomegaly in hemolytic anemia,

while computed tomography (CT) scanning is used to evaluate occult bleeding in blunt trauma (eg,
splenic rupture, subcapsular hemorrhage of the liver) or a bleeding disorder. Abdominal Doppler
study is used to detect portal vein thrombosis.

Radioactively tagged RBC radionuclide scans are occasionally used to localize the site of GI
bleeding when the source is unclear (a common example in pediatrics is the Meckel scan, used in
the diagnosis of Meckel diverticulum).

Family studies, such as sending the CBC count, smear review, and hemoglobin electrophoresis
from parents, may be helpful in making a diagnosis of conditions such as hereditary spherocytosis
or thalassemia.

Rarely indicated in isolated acute anemia, bone marrow aspiration and biopsy are indicated in the
evaluation of possible bone marrow failure or malignancy. Suppression of the platelet count or
white blood cell (WBC; neutrophil) count, in association with anemia, often warrants an
examination of the bone marrow.

Magnetic resonance imaging in research settings

Recently an MRI change termed acute silent cerebral ischemic events (ASCIE) in patients who
developed acute anemia with and without sickle cell disease has been described.[1] The MRI
abnormality is detected by diffusion-weighted imaging. The lesion may be temporary or long-
lasting. If it is a permanent MRI lesion and the patient has no over clinical symptoms attributable to
that lesion, then it is called a silent infarct. The fact that it occurs in children without sickle cell
disease may indicate that in acutely severely anemic children regardless of the cause, ASCIE may
not be a very rare event, and it does raise a question if some of these lesions are permanent and
may cause subtle neurological dysfunction. Although MRI cannot be a routine imaging study for
acute severe anemia, it may be a worthwhile test under a research setting.

Complete Blood Count

 Base interpretation of the hemoglobin and hematocrit levels on the reference range for the specific
age group. Some laboratories provide only a uniform reference range for the entire pediatric age
group and not for specific age groups. Hemoglobin and hematocrit levels can be used
interchangeably, depending on professional preference and familiarity. Essentially, the hematocrit
level is 3 times the hemoglobin value.

If the patient is anemic, look at the red cell indices (mean corpuscular volume [MCV], mean
corpuscular hemoglobin [MCH] and mean corpuscular hemoglobin concentration [MCHC]). Note
that reference ranges for these parameters also vary with age. Of these, the MCV is particularly
helpful in classifying anemia. Microcytic anemia suggests iron deficiency, lead poisoning, or
thalassemia; macrocytosis suggests folate/B-12 deficiency or reactive reticulocytosis.

Another valuable parameter in classifying anemia is the RBC distribution width(RDW). This is the
statistical description of the heterogeneity of RBC sizes. It is increased in anisocytosis (variable
sizes of red cells), such as when increased reticulocytes are present.

Reticulocyte Count
Reticulocytes are immature, nonnucleated RBCs that indicate active erythropoiesis. The
relative reticulocyte count is useful in differentiating whether the anemia is caused by decreased
production, increased destruction, or loss of RBCs. An elevated number of reticulocytes
(eventually) is observed in individuals with anemia caused by hemolysis or blood loss; note that
the absence of reticulocytosis may simply reflect a "lag" in the response to the acute onset of
anemia. Note that in some autoimmune hemolytic anemias, reticulocytopenia is present due to
lysis of reticulocytes by the same antibodies.

The term reticulocyte count is often used inaccurately to refer to the percentage of reticulocytes, a
value that must be interpreted in light of the degree of anemia. Thus, a finding of 2-3%
reticulocytes (vs the normal value of approximately 1%) in a patient whose hemoglobin is only one
third to one half of normal does not indicate a reticulocyte "response." Some clinicians prefer to
use either the absolute number of reticulocytes per µL of blood or a reticulocyte percentage
"corrected" for the degree of anemia, as follows: corrected reticulocyte count = patient
hematocrit/normal hematocrit x %reticulocyte count.

Peripheral Smear
Examination of the peripheral smear helps to identify the cause of the anemia through recognition
of abnormal cell morphology (this is particularly helpful in normocytic anemia). The following are
examples of abnormal cell morphology:

 Schistocytes or fragmented cells (microangiopathic hemolytic anemia)

 Spherocytes (hereditary spherocytosis, autoimmune hemolytic anemia)
 Ghost, helmet, blister, or bite cells (G-6-PD deficiency)
 Sickle-shaped cells (sickle cell disease)
 Target cells (hemoglobin C): These can be seen nonspecifically in other conditions, such as
thalassemia, other hemoglobinopathies, and with liver disease; however, hemoglobin C is the
classic, most common example
 Stippled red blood cells (nonspecific, but may suggest lead poisoning; occurs in any condition
with reticulocytosis)
 Increased polychromasia (reticulocytosis)
 Crenated or spiculated cells (liver disease, uremia, abetalipoproteinemia)
Recognizing that normal RBC morphology does not rule out hemolysis is important.

Additional Laboratory Tests

Additional laboratory tests that may be indicated in the diagnosis and treatment of patients with
acute anemia include the following:

 Bilirubin level, lactate dehydrogenase (hemolytic anemia)

 Direct antiglobulin or Coombs test (autoimmune hemolytic anemia)
 Hemoglobin electrophoresis (hemoglobinopathies) (many unstable hemoglobins, such as Hb
KÖLN, cannot be detected by hemoglobin electrophoresis)
 Red cell enzyme studies (eg, G-6-PD, pyruvate kinase)
 Osmotic fragility (spherocytosis)
 Iron, total iron-binding capacity (TIBC), ferritin (iron deficiency anemia)
 Folate, vitamin B-12 (macrocytic/megaloblastic anemia)
 Blood typing and crossmatching to assess possible isoimmune anemia in a neonate and to
prepare for transfusion
 Bone marrow aspiration and biopsy
 Viral titers (eg, Epstein-Barr virus, cytomegalovirus)
 Blood urea nitrogen (BUN) and creatinine levels to assess renal function
 Thyroxine (T 4)/ thyroid-stimulating hormone (TSH) to rule out hypothyroidism
 "Fetaldex test" on maternal blood (Kleihauer-Betke test), when fetomaternal transfusion is
suspected
 Stool for occult blood (on multiple specimens)
 Acute anemia usually warrants immediate medical attention. Treatment depends on the
severity and underlying cause of the anemia.

 Initial treatment begins with careful assessment of the signs and symptoms of the anemia
that indicate therapy. Guidelines for the treatment of patients with critical illness apply to
children with severe anemia who are in acute distress and unstable. Supportive
measures, such as supplemental oxygen for decreased oxygen-carrying capacity, fluid
resuscitation for hypovolemia, and bed rest or activity restriction for fatigue, may be
required. Inpatient care is indicated in patients with CHF who are severely anemic and in
those with unstable vital signs (eg, hypotension, active bleeding). Most of these patients
require admission to the intensive care unit (ICU). Patients who may be stable but who
have severe anemia may also be admitted for diagnostic workup.

 Except in cases of uncontrolled hemorrhage, surgery is very rarely indicated in acute

anemia. Splenectomy is occasionally considered in persons with autoimmune hemolytic
anemia that is refractory to medical treatment.

 Activity restriction or bed rest may be indicated in symptomatic individuals with severe
anemia.

 Transfusion with packed RBCs (PRBC) is the universal treatment for most individuals with
severe acute anemia. The British Committee for Standards in
Hematology Transfusion Task Force has established guidelines for transfusions in
neonates and older children.[10] and its amendments[11] The indication to transfuse should
not be based solely on the hemoglobin or hematocrit levels; more importantly, one must
consider the clinical effects or the signs and symptoms of the individual with anemia. [12]

 A recently published article summarizing 19 randomized controlled studies in adults

concluded that transfusions at a low Hb threshold level (7-9) compared with transfusions
at a high Hb threshold level (9-13.3) showed a significantly reduced risk of 30-day all-
cause mortality.[13] In another adult study with acute GI hemorrhage, restricted
blood transfusion (Hb threshold of 7) versus a liberaltransfusion strategy resulted in
significantly reduced morbidity and mortality in the former group of patients.[14] While these
are adult studies, the same principle may apply to children. Thus, one may consider these
clear-cut study results when considering blood transfusion for a patient.

 If transfusion is indicated, the packed RBC (PRBC) dose is 10-15 mL/kg over 3-4 hours.
The rate of transfusion can be modified according to the clinical situation.Transfusion can
be administered faster in individuals with acute blood loss or slower or in smaller aliquots
in persons with CHF. Be aware of the risks of of inciting heart failure by
rapid transfusion in patients with severe chronic anemia and patients in a compromised
cardiovascular state.

 In individuals with autoimmune hemolytic anemia, blood must be given with extreme
caution, using the blood unit that is least reactive on crossmatch

Except for patients who have acute anemia secondary to blood loss from obvious trauma or injury,
a hematology consultation is ideal for most patients with acute anemia to determine the underlying
RBC disorder and provide the appropriate therapy.

In particular, the following features in an individual with acute anemia indicate the need for a
hematology consultation:
 Concomitant abnormality in WBC and/or platelet counts (eg, neutropenia, thrombocytopenia,
presence of immature WBCs)
 Positive Coombs test result
 Hepatosplenomegaly
 History of underlying hematologic disorder
 Excessive blood loss relative to the degree of injury in individuals who may have an underlying
bleeding disorder
Consider a gastroenterology consult for GI blood loss, particularly in suspected esophageal
varices, inflammatory bowel disease, and other conditions.

Consider a surgical consult for possible trauma to spleen, liver, and/or kidneys.

Medication Summary
Medications for specific forms of anemia may be indicated in addition to blood transfusion (eg,
corticosteroids for autoimmune hemolytic anemia, iron therapy for iron deficiency anemia).

Recombinant erythropoietin has been available for the treatment of certain forms of anemia. Its
use can allow for avoidance or minimization of the need for blood transfusion. Indications include
anemias of chronic disease (eg, renal failure), chemotherapy, acquired immunodeficiency
syndrome (AIDS) treatment, preparation for surgery with anticipated significant blood loss,
prematurity,[15] and hyporegenerative anemia of erythroblastosis fetalis. It is important to note that
erythropoietin is not indicated for the immediate correction of anemia. The correction of anemia
with erythropoietin occurs after about 2-8 weeks.

Blood Products
Class Summary
The goal of therapy in acute anemia is to restore the hemodynamics of the vascular system and
replace lost red-blood cells. To achieve this, the practitioner may use blood transfusions. Major
complications of acute anemia can be prevented by providing timely transfusion to restore
hemoglobin to safe levels.

Packed red blood cells

Packed red blood cells (PRBCs) are used preferentially to whole blood since they limit volume,
immune, and storage complications. PRBCs have 80% less plasma, are less immunogenic, and
can be stored about 40 days (versus 35 days for whole blood). PRBCs are obtained after
centrifugation of whole blood. Whole blood is not available in many blood banks

Iron Salts
Class Summary
Iron salts are used for treating patients with iron deficiency anemia.

View full drug information

Ferrous Sulfate (Feosol, Fer-Iron, Slow FE)
Iron salts are used as building blocks for hemoglobin synthesis in treating anemia. They allow
transportation of oxygen via hemoglobin and are necessary for oxidative processes of living tissue.
Treatment should continue for about 2 months after correction of anemia and etiological cause in
order to replenish body stores of iron. Ferrous sulfate is the most common and inexpensive form of
iron utilized. Tablets contain 50-60 mg of iron salt. Other ferrous salts are used and may cause
less intestinal discomfort because they contain smaller doses of iron (25-50 mg). Oral solutions of
ferrous iron salts are available for use in pediatric populations.

Patient Education
In pediatrics beyond the immediate neonatal period, acute anemia is rare in otherwise healthy
children. In most instances, it is due to blood loss usually through GI tract or via heavy menstrual
period. Most common reason for hospitalization due to acute anemia is due to so called aplastic
crisis in children with chronic hemolytic anemia who otherwise had been stable. Most common
varieties are herediatrary spherocytosis and sickle cell disease. Therefore it would be prudent to
educate parents regarding this complication, at the time when the diagnosis is established.