Page 2485 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 152 Hematologic Manifestations of Childhood Illness 2217

typhoid fever and brucellosis, leukopenia and neutropenia are promi- in 6- to 12-month-old infants, and 0.6% in 11- to 15-year-old
nent early in the illness. Shigellosis is associated with a variable leu- children. Infection was the cause of the thrombocytosis in 67.5% of
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kocyte count, but the count often is normal, with a greater percentage the cases. Complications of reactive thrombocytosis are rare, but
of bands than neutrophils. Illnesses associated with lymphocytosis hemorrhagic or thrombotic complications may occur if there are
include pertussis (whooping cough), infectious lymphocytosis, infec- additional acquired risk factors. Antiplatelet therapy is not indicated
tious mononucleosis, and other viral infections. Neutropenia can be in patients with reactive thrombocytosis secondary to infection.
seen in bacterial sepsis from meningococci, pneumococci, staphylo- Although the most common cause of thrombocytosis in children is
cocci, and other bacteria and is associated with a poor prognosis. infection, the list of considerations in the differential diagnosis of an
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Black children (and adults) normally have lower WBC and neutrophil elevated platelet count is extensive and rarely includes underlying
counts than those seen in whites; leukocyte and neutrophil response childhood malignancy.
to serious infection may be decreased. 23
Thrombocytopenia
Neutropenia
Thrombocytopenia can be seen in patients who have infections with
The most common cause of neutropenia (neutrophil count <1500/µL) all types of organisms. Common viral agents include varicella virus,
in children is viral infection. A number of specific viruses are associ- EBV, influenza virus, rubella virus, mumps virus, measles virus (wild
ated with neutropenia, including hepatitis virus, roseola virus, rubella or vaccine strains), HHV-6, hepatitis A virus, and CMV. The primary
virus, mumps virus, adenovirus, coxsackievirus A21, EBV, human mechanism of the thrombocytopenia is immune destruction, although
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herpesvirus-6 (HHV-6), and influenza virus. The most common a direct viral effect on the platelet, megakaryocyte, or hematopoietic
clinical setting, however, is the incidental discovery of neutropenia in stem cell has been demonstrated. Because childhood ITP is thought
a child with a nonspecific viral syndrome. Usually the neutropenia in to be secondary to infection in most instances, the definitions of
this situation continues for less than 30 days and is rarely associated “thrombocytopenia with infection” and “childhood ITP” tend to
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with infectious or long-term complications. In one large study of merge. Thrombocytopenia from infection usually is transient,
1888 otherwise healthy children with fever and ANC counts below although instances of chronic thrombocytopenia from specific viral
1000/µL, there was only a 1.3% incidence of serious bacterial infec- infections (e.g., varicella or CMV) have been documented. 34,35
tion in children older than 3 months of age (1 bacteremia infection, Thrombocytopenia also is associated with bacterial sepsis. The low
13 urinary tract infections). The risk was higher in infants younger platelet count may be an isolated finding or associated with DIC.
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than 3 months of age (3.3%), similar to the risk of febrile infants of Corrigan documented a 61% incidence of thrombocytopenia in 45
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the same age without neutropenia. Neutropenia also has been children with sepsis. The degree of thrombocytopenia was mild to
associated with a number of bacterial, rickettsial, and fungal infec- moderate (64% had platelet counts >50,000/µL), but platelet counts
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tions. Although infection is the most common cause of transient ranged as low as 8000/µL. There was no evidence of DIC in 39% of
neutropenia in childhood, the febrile child discovered to have inci- those with low platelet counts. Thrombocytopenia in the setting of
dental neutropenia should have repeat blood counts done within 3 bacterial sepsis probably is also mediated by an immune mechanism
to 4 weeks to rule out chronic neutropenia. with elevated platelet-associated IgG.
Petechial bleeding without thrombocytopenia can be seen in both
bacterial and viral disease, especially that caused by meningococci,
Eosinophilia streptococci, and echoviruses. The explanation for the petechial rash
in these infections is either vasculitis or platelet dysfunction.
The most common cause of eosinophilia worldwide is parasitic infec-
tion. In the United States, visceral larva migrans (Toxocara infestation)
is the most common cause of exaggerated eosinophilia (WBC count Disseminated Intravascular Coagulation
30,000–100,000/µL with 50%–90% mature eosinophils) in chil- and Purpura Fulminans
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dren. Mild to moderate eosinophilia (≥600/µL) is most often seen
in children with allergic rhinitis or asthma but also is characteristic Disseminated intravascular coagulation is uncommon after child-
of chlamydial pneumonitis in infants. hood infections and, if present, usually is accompanied by shock,
with at least a 50% mortality rate. The most common organisms
Changes in Platelets or Coagulation producing DIC are bacterial, especially the gram-negative bacteria
(meningococci, H. influenzae, Aerobacter spp., and others) but also
gram-positive organisms (Staphylococcus aureus; group B streptococci;
Thrombocytosis S. pneumoniae, particularly in asplenic hosts; and Bacillus anthracis).
DIC also is associated with disseminated viral (varicella, measles, and
Thrombocytosis (platelet count >500,000/µL) is known as an acute- rubella), rickettsial (Rocky Mountain spotted fever), fungal, myco-
phase reaction to infection, but it has been infrequently identified in plasmal, and parasitic infections.
children in the past. There is a particularly high incidence of reactive Purpura fulminans is a rare syndrome, seen in extremely ill chil-
thrombocytosis in patients with bacterial infections, especially pneu- dren with DIC. Purpura fulminans is characterized by the rapid
monia with emphysema, and H. influenzae meningitis. Inflammatory progression of ecchymotic skin lesions, especially of the extremities,
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cytokines, such as interleukin (IL)-1, IL-6, and thrombopoietin, may that may progress to gangrene, ultimately resulting in amputation.
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play an etiologic role in the reactive thrombocytosis of infection. This syndrome has been described as a postinfectious purpura, with
The vast majority of children with thrombocytosis have platelet scarlet fever, upper respiratory tract infection, and varicella as the
counts between 500 and 700,000/µL, but 6% to 8% have counts most common preceding illnesses and a latent period of 0 to 90 days
between 700 and 900,000/µL and only 0.5% to 3% have platelet after infection. A similar clinical picture can be seen in children with
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counts above 1,000,000/µL. Thrombocytosis may be more common DIC and acute bacterial sepsis, especially meningococcemia.
in simple acute infections than was previously recognized. Heath and Increasing evidence indicates that DIC with purpura fulminans is
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Pearson documented a 13% incidence of thrombocytosis in ambu- associated with deficiency of the naturally occurring anticoagulants.
latory patients; children with an increased platelet count were more Children with postviral purpura fulminans have been shown to have
likely to have a diagnosis of infection. In a Japanese study of more acquired protein S deficiency, anti–protein S antibody, or the pres-
than 7500 hospitalized patients with platelet counts greater than ence of a lupus anticoagulant. 38,39 In children with infectious purpura,
500,000, 6% of patients had thrombocytosis with an age-dependent protein C activation is impaired, as reflected in low levels of protein
incidence: 12.5% in neonates, 35.8% in 1-month-old babies, 12.9% C, protein S, and antithrombin. These findings are consistent with