Page 2483 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 152

HEMATOLOGIC MANIFESTATIONS OF CHILDHOOD ILLNESS

Arthur Kim Ritchey, Sarah H. O’Brien, and Frank G. Keller

The hematologic response to systemic illness in children is similar to joint infections, typhoid fever, brucellosis, and invasive Haemophilus
that in adults. A number of disorders occur more frequently in influenzae infections.
children, however, and some are unique to the pediatric population. The anemia associated with H. influenzae meningitis is the most
In addition, interpretation of the hematologic response is predicated thoroughly studied of the anemias of acute infection to date. A
on knowledge of the normal developmental changes that occur majority of children with H. influenzae meningitis have mild anemia
within the hematopoietic system throughout childhood (Table on admission, with hemoglobin in the 9–11 g/dL range, and up to
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152.1). This chapter focuses on the hematologic manifestations of 90% become anemic during the course of the illness. This is in
common or unique systemic diseases that occur in neonates, children, contrast with meningitis secondary to Streptococcus pneumoniae or
and adolescents. Illnesses that often require hematologic consultation Neisseria meningitidis, in which anemia is uncommon. The patho-
are emphasized. Systemic diseases that produce hematologic abnor- physiology of the anemia of H. influenzae disease appears to be
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malities that are similar in adults and children are discussed in other multifactorial. Shurin and associates have shown that H. influenzae
chapters. For a comprehensive review of the subject, readers are capsular polysaccharide, polyribosylribitol phosphate, binds to
referred to a published textbook. 1 erythrocytes, which, in the presence of antibody and complement,
can result in intravascular and extravascular hemolysis. They further
hypothesize that polyribosylribitol phosphate alone may induce more
INFECTIOUS DISEASE rapid clearance of RBCs, perhaps on the basis of decreased RBC
deformability. In addition, hypoferremia may limit bone marrow
Infection, especially viral infection, is the most common problem response to hemolysis. As a result of immunization with pneumococ-
encountered by pediatricians. Although most infections do not cal and H. influenzae vaccines in early childhood, it is uncommon to
produce significant hematologic sequelae, all classes of microorgan- see infections secondary to these organisms currently.
isms have been implicated in the pathogenesis of hematologic
abnormalities that range from mild and clinically irrelevant to severe
and life threatening. This section describes the changes seen in red Acute Hemolytic Anemia
blood cells (RBCs), white blood cells (WBCs), platelets, and the
coagulation system that are routinely encountered, are associated with Acute hemolysis has been observed with infections from all classes of
a specific infection, or have a potentially serious clinical impact. microorganisms but is relatively uncommon. The anemia may be
mild to severe, and the condition is manifested in children in either
of two ways: (1) clinical presentation with symptoms and signs of
Changes in Red Blood Cells infection predominating in a child subsequently found to have
anemia or (2) clinical presentation with the manifestations of acute
The anemia of chronic inflammation or infection in children is hemolytic anemia.
similar to that seen in adults in terms of both clinical and hematologic The mechanism of hemolysis in patients presenting with an infec-
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findings and pathogenesis. However, anemia with acute infections tious disorder depends on the infecting organism, but hemolysis is
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occurs more commonly in children than in adults. extravascular in most cases. Reported mechanisms include the
following:
Anemia of Acute Infections • Release of hemolysins (Clostridium perfringens sepsis)
• Invasion of the RBCs (malaria)
A mild to moderate anemia of uncertain etiology may occur in the • Alteration of the RBC surface:
setting of both acute viral infections and more serious bacterial infec- Direct adherence by the organism (Bartonella spp.)
tions. In a study of children with mild viral or bacterial infections in Alterations of antigenic phenotype by neuraminidase (influenza
the outpatient setting, anemia was documented in 5% of children 4 virus)
to 12 years of age, 17% of children 6 months to 4 years of age, and Cold agglutinins (Mycoplasma spp., Listeria spp., Epstein-Barr
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33% of infants 6 to 11 months of age. In 14 of 15 young children, virus [EBV], Leptospira spp., Rubella spp. )
the anemia resolved within 3 to 4 weeks. However, multiple mild Absorption of capsular polysaccharide (H. influenzae)
infections may predispose infants to the development of a more
chronic, mild anemia or low-normal hemoglobin that may be caused • Mechanical mechanisms (microangiopathy associated with dis-
by iron deficiency, thus warranting a trial of iron supplementation. seminated intravascular coagulation [DIC] or hemolytic uremic
Among children hospitalized with moderately severe inflamma- syndrome [HUS])
tory processes, the incidence of mild anemia (hemoglobin, 10.1– • Oxidative damage in persons with congenital enzyme deficiencies
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11.0 g/dL) is as high as 78%. In a study of hospitalized children (e.g., hepatitis or brucellosis with glucose-6-phosphate dehydro-
with either pyelonephritis bacteremia, average age 5 to 6 years, 60% genase [G6PD] deficiency, Campylobacter jejuni infection in
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had anemia. No evidence of hemolysis was seen in this group of neonates)
children. Follow-up hemoglobin measurements in a subset of patients
showed levels had returned to normal without specific intervention. Acute, infection-associated hemolytic anemia in one study lagged
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These data suggest that there is no indication to investigate the mild behind the clinical infection by 3 to 7 days. Most children were
anemia of acute infection. Specific acute bacterial infections associ- shown to have adsorption of microbial antigens to the RBC surface,
ated with a high incidence of anemia (44%–74%) include bone and suggesting an “innocent bystander” mechanism of erythrocyte
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