Page 2487 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 152 Hematologic Manifestations of Childhood Illness 2219

neutropenia associated with opportunistic infections. Immune neu- hypochromic. The reticulocyte count usually is low. Iron studies often
tropenia and also circulating anticoagulants have been described. show low serum iron, increased free erythrocyte protoporphyrin,
Lymphopenia is progressive but less prominent in children than in low-normal or elevated total iron-binding capacity, and normal or
adults until late in the course. low serum ferritin. Serum erythropoietin levels usually are mildly
Thrombocytopenia is present in 13% to 30% of pediatric patients elevated (but not as high as in iron deficiency). The bone marrow
with AIDS and can be associated with clinically significant and even does not show erythroid hyperplasia in response to the anemia and
fatal hemorrhage, although in the modern era of highly active anti- has diminished (but not absent) iron stores. The etiology of the
retroviral therapy (HAART), the incidence in adults is as low as anemia may be chronic disease, iron deficiency, or both.
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0.6%. The mechanism of the thrombocytopenia in most cases is Although it is difficult to differentiate anemia of chronic disease
immune destruction, with a high percentage of patients having from iron-deficiency anemia, studies in patients with systemic-onset
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antiplatelet antibodies or immune complexes, although amega- chronic JIA suggest defective iron supply as the primary cause.
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karyocytic thrombocytopenia has been reported. Variable therapeu- Transferrin receptor levels are inversely related to hemoglobin levels
tic responses to both corticosteroids and intravenous IgG have been in this population. The finding of elevated serum transferrin receptor
demonstrated; some children have spontaneous remissions. 82,83 Treat- levels may be a reliable indicator for diagnosis of iron deficiency in
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ment with ART has resulted in an increase in the platelet count in JIA. Oral iron has been effective in raising the hemoglobin in
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some children. Thrombosis has also been described and is associated iron-deficient anemic patients with JIA, and intravenous iron has
with severe disease. 85 been effective in raising the hemoglobin level in children unresponsive
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Isolated thrombocytopenia as a presenting manifestation of HIV to oral iron. Excessive production of IL-6, tumor necrosis factor-α
infection has been reported in a number of children, usually infants (TNF-α), and other inflammatory cytokines has been documented
and even in a neonate. 65,86 There have been no associated clinical in patients with JIA and may provide an explanation for the abnor-
stigmata of AIDS or ARC, and patients have been responsive to malities in iron metabolism. IL-6 may enhance ferritin synthesis and
standard treatment (intravenous IgG or prednisone), often with increase hepatic uptake of serum iron. Increased ferritin results in
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sustained remissions. In a few patients with prolonged follow-up, no reticuloendothelial iron blockage and diminished iron absorption.
further manifestations of HIV infection were seen. Although it has In one study of treatment with anti–TNF-α therapy, the hemoglobin
been suggested that HIV testing may be indicated in all children with as well as markers of abnormal iron metabolism improved signifi-
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ITP, it seems most reasonable to check the HIV status of those with cantly. Less common causes of anemia in patients with JIA include
risk factors for AIDS and those outside the typical age group for ITP, erythroid aplasia, suppression of erythropoiesis by circulating inhibi-
especially infants. tors, hemolysis, and a macrocytic anemia probably related to increased
folate clearance and low plasma and RBC folate levels.
In sJIA, leukocytosis with mean WBC counts up to 30,000/µL
COLLAGEN VASCULAR DISEASE AND and neutrophilia with a left shift occur in 90% of patients, especially
those with active disease. Leukocytosis is less common in polyarticular
ACUTE VASCULITIS arthritis and usually absent in pauciarticular disease. Leukocytosis is
so prevalent in sJIA that the presence of neutropenia should alert the
Juvenile Idiopathic Arthritis clinician to question the diagnosis and ensure that other possibilities
such as systemic lupus erythematosus (SLE) and ALL are not over-
Juvenile idiopathic arthritis (JIA) (formerly called juvenile rheumatoid looked. Nonetheless, neutropenia has been reported in several patients
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arthritis) includes a group of disorders with varied clinical presenta- with JIA. Other causes of neutropenia are bone marrow suppression
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tions, courses, and outcomes. Systemic juvenile idiopathic arthritis caused by therapy with tocilizumab, gold, or nonsteroidal antiin-
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(sJIA), which occurs in 10% of patients, is a multisystem disease flammatory drugs (NSAIDs), and, in adults, Felty syndrome,
characterized by fever, rash, polyarticular (often destructive) arthritis, comprising the triad of rheumatoid arthritis, splenomegaly, and
hepatosplenomegaly, and lymphadenopathy. New understanding of neutropenia.
the pathogenesis of sJIA points to abnormalities in innate immunity The platelet count is elevated in about half of the patients with
(cytokines IL-1, IL-6, IL-18, neutrophils, and macrophages), distin- sJIA. IL-6, a cytokine that stimulates thrombopoiesis, is elevated in
guishing it from other forms of JIA, suggesting sJIA is an autoinflam- patients with active sJIA, and increased levels of IL-6 are correlated
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matory syndrome rather than an autoimmune disease. Another with elevated platelet counts. Persistent thrombocytosis may serve
distinguishing feature of JIA is the association with macrophage as an adverse prognostic marker for long-term outcome in JIA.
activation syndrome (MAS) (see later discussion). Patients with JIA Thrombocytopenia may result from bone marrow suppression by
commonly demonstrate hematologic abnormalities that are propor- gold therapy, the rare consumptive coagulopathy, or platelet trapping
tional to disease activity. In the polyarticular presentation, more than in Felty syndrome. Thrombocytopenia is also seen in the potentially
four joints are involved, but the systemic findings are absent. This life-threatening complication of MAS (see discussion of MAS below).
group, which accounts for 25% of patients, also may exhibit hema- Because thrombocytopenia is uncommon in JIA, however, an unex-
tologic abnormalities. Pauciarticular JIA is characterized by involve- plained low platelet count should lead the clinician to consider
ment of fewer than four joints and is rarely associated with hematologic alternative diagnoses, such as SLE or ALL. On the other hand, iso-
abnormalities. lated thrombocytopenia may be the only presenting sign in a child
Children with ALL may have a similar presentation to that of who later develops JIA or another collagen vascular disease. Therefore
children with sJIA, which includes fever, joint pain, hepatospleno- JIA and SLE should be considered in the differential diagnosis of ITP
megaly, and isolated cytopenias. Because about 5% of children with in children who are older than 9 years of age and female. Appropriate
ALL are misdiagnosed as having JIA, before initiation of corticoste- screening tests for autoantibodies (e.g., antinuclear antibody assay,
roid therapy, it is important to perform bone marrow aspiration to direct Coombs test) should be performed at diagnosis and periodi-
rule out leukemia in any patient thought to have sJIA. Distinguishing cally if new symptoms develop.
features of children ultimately diagnosed with ALL after referral to a Disseminated intravascular coagulation may occur in children
rheumatologist include atypical pattern of pain (nonarticular bone with sJIA after hepatic damage, as part of the MAS, from aspirin or
pain and night pain with no morning stiffness) and cytopenias, gold therapy, or during disease flare-ups treated with NSAIDs when
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especially thrombocytopenia. 65 serum albumin is low. These patients often are very ill and may
The incidence of anemia is 50% to 60% in patients with systemic require early and aggressive medical therapy as well as platelet and
or polyarticular JIA and 10% in those with pauciarticular arthritis. coagulation factor replacement to control the coagulopathy. The
The anemia usually correlates with disease activity, worsening during incidence of coagulation abnormalities in nonbleeding patients with
acute flare-ups; however, there is no relationship to the duration of sJIA is controversial. One study demonstrated prolonged prothrom-
illness. RBCs may be normochromic/normocytic or microcytic/ bin time (PT) and activated partial thromboplastin time (aPTT) and