Pediatric emergency medicine trisk 551

corpuscular volume is low. The RBCs are hypochromic and microcytic, with striking
variation in size and shape; nucleated RBCs are present on the peripheral smear.
Children and adolescents with thalassemia intermedia have a moderate anemia, with
hemoglobin levels usually between 7 and 10 g/dL. Hemoglobin electrophoresis is used
to make the initial diagnosis of β-thalassemia, although in many cases, index of
suspicion is high due to family history. Hemoglobin electrophoresis may also reveal
other variant β-chains such as hemoglobin E or C. Independently, these hemoglobins
may not cause a significant clinical phenotype; however, in combination with a β0 or β+
mutation, patients may have a β-thalassemia major or intermedia phenotype.
Patients with β-thalassemia major require lifelong transfusion or bone marrow
transplantation. Gene therapy options are presently in clinical trials. Patients may
present to the emergency department with symptoms of severe anemia prior to initial
diagnosis or later in life due to toxicity related to iron overload (often due to poor
compliance with iron chelation therapy). The β-thalassemia intermedia phenotype is
variable, but patients typically only need transfusions for acute exacerbations of their
anemia during illness, pregnancy, or perioperatively. Patients who carry one mutated βgene are asymptomatic but their red cells are microcytic (low MCV) and a mild anemia
may be evident.
The α-thalassemia gene mutations occur most commonly in populations living in
Mediterranean countries, northern Africa, the Middle East, India, and Southeast Asia.
Loss of one or two of the four α-globin genes is clinically trivial and manifests as a
silent carrier or α-thalassemia trait, respectively. Loss of three α-globin genes causes
hemoglobin H disease, usually associated with a moderate anemia and chronic
hemolysis. Loss of all four α-globin genes results in production of Hemoglobin Barts (γ4
) and hydrops fetalis (stillborn or death soon after birth). Hemoglobin electrophoresis
does not aid the diagnosis of α-thalassemia trait but can identify hemoglobin H.
Hemoglobin Barts can be detected on newborn screen.
Congenital and Acquired Aplastic/Hypoplastic Anemia
The differential diagnosis of aplastic and hypoplastic anemias is discussed in Chapter 62
Pallor . DBA and transient erythroblastopenia of childhood (TEC) are the more common
causes of pure RBC aplasia in early childhood. In DBA, the level of RBC adenosine
deaminase (ADA) is frequently elevated, and blood samples for this test should be

obtained before transfusion. TEC typically presents in previously healthy children from
infancy to toddlerhood with severe anemia and reticulocytopenia but otherwise normal
blood counts. For patients with a hypoplastic anemia suggestive of TEC, a bone marrow
aspirate may be helpful in predicting the course of the disease during the next few days
and, in particular, the likelihood that pRBC transfusions will be required. For example,
if a patient with TEC has a hemoglobin level of 4 g/dL, low reticulocyte count, and few
RBC precursors on bone marrow evaluation, a further decrease in the hemoglobin
concentration should be anticipated and pRBC transfusions will almost certainly be


required. However, if the bone marrow aspirate shows numerous erythrocyte precursors
progressing through all levels of erythrocyte maturation, a peripheral reticulocytosis can
be expected within 24 hours and RBC transfusions may be unnecessary.
Nutrition Deficiencies and Excess
Nutritional anemias in children constitute more of a public health problem than a
hematologic emergency; however, in some cases, the hemoglobin level may be very low
at the time of diagnosis. Some of the most common micronutrients related to anemia
include deficiencies of iron, B12 , folate, zinc, vitamin C, and excess of copper. Of these,
iron-deficiency anemia is the most common in the pediatric population.
Severe iron deficiency occurs mainly in toddlers due to excess cow’s milk
consumption (more than 1 quart [32 fl oz or ∼1 L] daily). Adolescent girls make up
another group at high risk for iron deficiency because a diet normally marginal in iron
content becomes inadequate in the face of menstrual blood losses. The presenting
complaints in severe iron-deficiency anemia include pallor, lethargy, irritability, or poor
exercise tolerance. Iron replacement therapy consists of 3 to 6 mg/kg/day of elemental
iron given orally as ferrous sulfate at night on an empty stomach (and ideally with
ascorbic acid) as a single daily dose. The hematologic response to parenterally
administered iron is no faster than the response to orally administered iron for patients
with intact gastrointestinal absorption. Historically, intravenously administered iron has
been associated with anaphylaxis, but such reactions are rare with modern preparations.

Vitamin B12 and folate deficiency result in megaloblastic macrocytic anemia. Infants
exclusively breast-fed by a vegetarian mother may develop vitamin B12 deficiency.
Nutritional deficiencies may also be seen with other restrictive diets. In folic acid
deficiency caused by impaired folate absorption, nonhematologic symptoms such as
diarrhea, slowed development, or altered mental status and coma may be more
prominent than the symptoms of anemia. When considering replacement of folic acid or
vitamin B12 , traditional replacement doses of 1 mg of folic acid and 100 mcg of vitamin
B12 daily are undoubtedly excessive, but their common use reflects the safety and
concentrations of the available compounds. The administration of supplemental iron,
vitamin B12 , or folic acid should not be considered a substitute for adequate dietary
intake when nutritional deficiency is recognized. Unlike most hematologic emergencies,
the rapid improvement after treatment of these disorders may reduce the likelihood of
further visits despite attempts to ensure adequate follow-up care. Therefore, a strong
effort to restructure the diet should begin at the time of the initial contact.

Clinical Considerations
Clinical Recognition
Patients with congenital and acquired disorders of RBC production may be detected
incidentally, with mild symptoms such as pallor, fatigue or malaise, or due to severe


symptoms such as cardiopulmonary compromise. Some viral infections, such as
parvovirus, may suppress erythropoiesis which can precipitate an anemic crisis in a
previously stable patient with a chronic process. A mild anemia due to chronic disease
may be the presentation of a child with systemic illness. Age of onset helps to guide
differential diagnosis. While acquired etiologies can arise at any age, congenital forms
of aplastic anemia and thalassemia major typically present during infancy or early
childhood.
Initial Assessment/H&P
History should include a thorough review of systems including general complaints of

fatigue or decreased exercised tolerance, dietary history, family history and ethnic
origin, and menstrual history where appropriate. Physical examination should assess for
lymphadenopathy, organomegaly, and signs of bleeding.
Diagnostic Testing
Laboratory testing should include a CBC, reticulocyte count, review of peripheral blood
smear, type and cross, concentration of reticulocyte hemoglobin (CHr), indirect antibody
test (i.e., indirect Coombs test), and DAT (i.e., Coombs test), total and direct bilirubin,
ferritin, plasma iron, total iron-binding capacity (TIBC), chemistry panel, urinalysis, and
a stool examination for occult blood. Additional testing including hemoglobin
electrophoresis, micronutrient levels, ADA activity, genetic testing for congenital
aplastic anemias may also be appropriate and should be guided by consultation with a
hematologist. Often these subspecialized tests are not interpretable in the weeks
following a transfusion, so communication with hematology prior to transfusion is
preferable if clinical situation permits.
Management
The decision regarding transfusion of pRBCs depends on the etiology and severity of
the anemia. Replacement of nutrient deficiencies and elimination of toxin exposures are
necessary ( Table 93.5 ). If the hemoglobin level is mildly decreased from baseline
levels and the patient has no evidence of cardiovascular compromise, transfusion may
be unnecessary. However, transfusion should be considered in any patient with
cardiovascular compromise, or borderline cardiovascular symptoms in the setting of
expected ongoing losses. The goal of transfusion should be relief of symptoms, not
restoration of a normal hemoglobin level. If transfusion is necessary, provide small
aliquots of pRBCs (5 mL/kg) slowly. The administration of a rapid-acting diuretic
(furosemide 1 mg/kg/dose, maximum 20 mg/dose) may diminish the risk of fluid
overload.
For patients requiring recurrent or chronic transfusions or patients who may be
candidates for bone marrow transplantation, blood bank measures to provide CMVnegative products and reduce the likelihood of alloimmunization by leukoreduction of

pRBC units or extended RBC antigen typing are beneficial. First-degree relatives should
not be chosen as blood donors to avoid allosensitization to family minor HLA antigens.

SICKLE CELL DISEASE
Goals of Treatment
Patients with sickle cell disorders suffer from three broad categories of complications:
vascular occlusion, infection, and end-organ damage. Immediate recognition and early
management of these complications can prevent hospitalizations, decrease the need for
significant interventions such as exchange transfusions, and avoid long-term morbidity
and death.