Pediatric emergency medicine trisk 302

Hemoglobinopathies
Pallor may result from the low hemoglobin level found in patients with sickle cell
anemia and related hemoglobinopathies. Acute accentuation of pallor can result
from an aplastic crisis, a complication of hemolytic disorders that is particularly
common in sickle cell anemia. During an aplastic crisis, the normally elevated
reticulocyte count may fall to zero, and the hemoglobin level may fall as low as 1
to 2 g/dL, resulting in severe pallor and signs of high-output cardiac failure.
The sequestration crisis of sickle cell anemia (HbSS) and related hemoglobin
disorders (SC disease, S-β0–thalassemia, S-β+ –thalassemia) is a true hematologic
emergency. The presence of increased pallor and acute enlargement of the spleen
in a patient with a sickling disorder should prompt immediate investigation of
possible sequestration crisis. The condition results from pooling of red cells and
plasma in the spleen resulting in sudden and severe anemia with associated
hypovolemia. Emergent intervention is warranted as untreated cases may rapidly
lead to death. Although this complication rarely occurs in children with
homozygous SCD or S-β0–thalassemia after the age of 5, sequestration crises
may occur much later in children with sickling disorders such as SC disease or Sβ+ –thalassemia, in which early splenic infarction is less common.

Immune Hemolytic Anemia
Pallor caused by autoimmune hemolytic anemia is usually acute in onset and may
be associated with severe anemia. Symptoms may include jaundice, dark urine,
splenomegaly, and cardiovascular derangement. The presence of only moderate
anemia (6 to 8 g/dL) at diagnosis should not detract from consideration of this
disease as a hematologic emergency because brisk hemolysis may result in a
sudden, additional fall in hemoglobin level. Autoimmune hemolytic anemia is
usually, but not always, characterized by a positive direct antiglobulin (Coombs)
test and an increased reticulocyte count. Spherocytes are commonly seen in the
peripheral smear. Other causes of immune hemolytic anemia include infections,
drug exposure, inflammatory diseases, and malignancies.

Microangiopathic Anemia

Alterations in the normal laminar flow of blood through the vascular system may
cause increased red cell destruction. In DIC, abnormal fibrin deposition within
small blood vessels results in mechanical injury to the erythrocytes.
Thrombocytopenia and clotting abnormalities, which often herald the onset of
DIC, may also contribute to the anemia via blood loss. The main diagnostic
findings are red cell fragments in the peripheral blood smear, with platelet and
clotting abnormalities typical of a consumptive coagulopathy (see Chapter 93


Hematologic Emergencies ), and the clinical features of an underlying entity such
as septic shock or extensive trauma, with which DIC is associated.
The increased red cell destruction in HUS and thrombotic thrombocytopenic
purpura (TTP) is also caused by intravascular fibrin deposition.
Thrombocytopenia and uremia may lower the hemoglobin concentration even
further via blood loss, impaired red cell production, shortened red cell survival,
and increased plasma volume. In some instances, anemia may be severe despite
only mild uremia and absent thrombocytopenia, raising doubt about the diagnosis.
In more typical cases, however, the diagnosis is readily apparent from the
findings of oliguria, central nervous system abnormalities, increased blood urea
nitrogen, thrombocytopenia, and abnormalities of red cell morphology on
peripheral blood smear, including fragments and helmet cells.
Another form of microangiopathic anemia involves the proliferation of blood
vessels within a cavernous hemangioma that may trap red cells or initiate a
localized consumptive coagulopathy, causing erythrocyte destruction. Anemia in
these cases is rarely severe unless the thrombocytopenia, which is more typical of
the disorder, contributes to chronic blood loss.

Blood Loss
Pallor resulting from sudden, massive hemorrhage is commonly secondary to
trauma; it is usually accompanied by signs of hypovolemic shock and evidence of

injury. Patients may present in compensated or decompensated hypovolemic
shock (see Chapter 10 Shock ) and need to be emergently managed. Alternatively,
the repeated loss of smaller amounts of blood over time may be associated with
few findings other than pallor. The finding of iron-deficiency anemia despite
normal dietary iron intake or iron supplementation may be a clue to the presence
of chronic blood loss from the gastrointestinal (GI) tract or less commonly within
the lungs or urinary tract.

EVALUATION AND DECISION
The initial assessment of the child with pallor should include an immediate
determination of the severity of illness. Rapid evaluation and intervention is
imperative for the severely ill child. In the presence of hypovolemic shock,
immediate support of vascular volume is required. When high-output cardiac
failure from severe anemia occurs, transfusion with small aliquots of packed red
cells is necessary. After stabilization with initial therapeutic efforts, a thorough
evaluation of the anemia can proceed.
If the child with pallor is not acutely ill, a deliberate search for the cause of
pallor should be undertaken ( Fig. 62.1 ). This may be accomplished by obtaining


a thorough yet focused history, performing a detailed physical examination, and
ordering appropriate laboratory investigations. The history should focus on
several major components. First, particular attention should be paid to the rapidity
of onset of pallor. The slow development of pallor suggests diminished red cell
production, as is found in bone marrow aplasia or iron deficiency. However, the
acute onset of pallor is consistent with the brisk hemolysis of autoimmune
hemolytic anemia, the splenic sequestration of SCD, or rapid blood loss.
After establishing the time course of the anemia, the history can be directed
toward categories of anemia or specific diseases. A detailed dietary history, with
particular attention to milk intake, is important in young children with suspected

iron deficiency as excessive consumption of cow’s milk often results in iron
deficiency. Vitamin B12 deficiency may accompany strict vegetarian diets from
which meat and egg products are excluded and may occur in breast-fed infants of
vegetarian mothers or mothers with pernicious anemia. Nutritional folic acid
deficiency is rare and can usually be readily deduced from the presence of severe
dietary alterations and evidence of other vitamin deficiencies.
The family history helps in the diagnosis of hemoglobinopathies and inherited
disorders of red cell membranes and enzymes. Because results of previous
hemoglobin testing may have been explained inadequately or recalled
inaccurately, a negative family history or newborn screening for
hemoglobinopathies should not preclude evaluation of the patient’s hemoglobin
phenotype if a sickling disorder is suspected. The presence of a microcytic
anemia unresponsive to iron in the parents suggests a thalassemic disorder. A
history of splenomegaly, splenectomy, or cholecystectomy in family members
may help identify a hemolytic disorder such as hereditary spherocytosis or
pyruvate kinase deficiency.
Finally, a well-directed review of systems is essential in looking for systemic
disorders such as chronic renal disease, hypothyroidism, or JIA. Pallor may be the
presenting complaint in these and other disorders.
In the examination of the anemic patient, pulse and blood pressure (BP) should
be measured to be sure hypovolemic shock and high-output cardiac failure are
neither present nor imminent. If anemia or volume loss is mild, tachycardia may
be present with a preserved BP. A systolic flow murmur is often heard if the
hemoglobin level is below 8 g/dL. In the severely anemic patient, pallor of the
skin and mucous membranes is usually readily apparent. When anemia is less
severe or when the skin color is dark, pallor may be appreciated only in the nail
beds, palmar surfaces, lips, and palpebral conjunctiva. Lymphadenopathy and
splenomegaly may suggest a malignancy or an infectious disease such as

mononucleosis. When splenomegaly occurs without lymphadenopathy, however,
attention is drawn to hemolytic disorders such as hereditary spherocytosis and
autoimmune hemolytic anemia or hemoglobinopathies (e.g., sickling disorders or
thalassemia major). Scleral icterus may also be present in these disorders of
shortened red cell survival. The finding of an unusually large and firm spleen in
the absence of increasing scleral icterus suggests that red cells are being
sequestered (e.g., splenic sequestration crisis of SCD, hypersplenism).
The skin in a patient with pallor should be examined for evidence of
underlying disorders. The presence of hemangiomas might suggest
microangiopathic anemia. If increased bruising or bleeding accompanies pallor,
multiple blood elements are probably affected. The circulation time of platelets is
short in comparison with that of red cells. Therefore, clinical findings of
thrombocytopenia are often present by the time pallor develops in patients with
acquired aplastic anemia, Fanconi anemia, and acute leukemia. Clinical evidence
of thrombocytopenia may also suggest micorangiopathic anemia as described
earlier. Sources of internal or external blood loss should be carefully sought.
Chronic GI bleeding may escape detection until iron-deficiency anemia develops.
Similarly, small pulmonary hemorrhages associated with idiopathic pulmonary
hemosiderosis are often mistaken for other pulmonic processes until several
recurrences of iron-deficiency anemia suggest a hidden site of blood loss. Bony
abnormalities associated with red cell disorders include frontal bossing from
compensatory expansion of the bone marrow in hemolytic diseases and upper
extremity anomalies found in some patients with Fanconi anemia.