Page 2493 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 152 Hematologic Manifestations of Childhood Illness 2225

development of anemia. Examples include antral gastritis, duodenal cytopenias. The association of the autoimmune polyglandular syn-
and colonic polyps, parasitic infestations, and GI malignancies. GI drome, a heterogeneous group of disorders, and pernicious anemia
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stromal tumors, although rare, usually present in teenage girls with has been reported in children. Additionally, the immunodysregula-
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anemia related to GI blood loss. In a recent report of small experi- tion, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome,
ence of endoscopic evaluation of the upper GI system in children and which is caused by loss-of-function mutations of the FOXP3 gene,
teenagers between the ages of 9 and 17 years presenting with iron- has been associated with immune cytopenias, including hemolytic
deficiency anemia who did not have hematologic or chronic diseases, anemia, neutropenia, and thrombocytopenia. 232
heavy menstrual flow or obvious blood loss demonstrated abnormal
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findings in 57% of patients. This small study suggests that careful
evaluation of the GI system should be considered in children and ANOREXIA NERVOSA
adolescents with unexplained iron-deficiency anemia and in those in
whom the iron deficiency does not correct appropriately with oral Anorexia nervosa is a psychiatric disorder occurring in about 1 in 800
iron supplementation. adolescent girls; it is characterized by an inability to maintain a
minimal normal body weight, intense fear of being fat, body image
distortion, and amenorrhea. The profound weight loss is accompa-
ENDOCRINE DISEASE nied by hypothermia, hypotension, edema, lanugo, and metabolic
changes and is associated with a mortality rate of 5% to 18%. A mild,
Hematologic Manifestations of Thyroid Disorders normochromic, normocytic anemia with reticulocytopenia occurs in
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about 30% of patients. Acanthocytes or spur cells have been
The associations between thyroid disorders and hematologic abnor- reported and may be caused by low serum α-lipoprotein levels. The
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malities are diverse. The most commonly reported findings include causes of the anemia probably are decreased RBC production and a
anemia of several etiologies and abnormalities of hemostasis. Specific relative increase in plasma volume. A few patients have had slightly
associations in childhood and adolescence appear to be less common decreased RBC survival. Serum vitamin B 12 and folate levels usually
than in adults. However, some rare disorders with both hematologic are normal. Despite low serum iron and decreased bone marrow iron
and thyroid manifestations appear to be particularly pertinent to the stores in 80% of patients, iron-deficiency anemia is uncommon
pediatric population. except during recovery, when iron supplementation is necessary. The
Congenital hypothyroidism has multiple etiologies, including severe hypophosphatemia seen during refeeding of severely malnour-
thyroid agenesis, thyroid-stimulating hormone resistance, disorders ished patients has been associated with hemolytic anemia.
in thyroid hormone production, and central hypothyroidism. Up to 50% of patients have leukopenia, with an absolute decrease
Screening programs for congenital hypothyroidism have been widely in numbers of neutrophils, lymphocytes, and monocytes. 234,235 The
adopted as part of neonatal screening programs for several decades, neutropenia may be quite severe. An increased incidence of infection
resulting in marked improvement in the clinical manifestations of is not usual, although with increasing use of central venous catheters,
235
congenital hypothyroidism. A series of 50 infants with congenital more serious bacterial infections are being reported. Bone marrow
hypothyroidism identified by neonatal screening found that modest reserves are normal despite marrow hypoplasia and a normal to
normocytic, normochromic anemia, correlating with the severity of slightly decreased size of the marginal pool. Impaired neutrophil
the hypothyroidism, is present during the first year of life despite chemotaxis, intracellular killing of staphylococci, and decreased
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thyroid hormone replacement. By comparison, a separate publica- complement levels have been demonstrated in patients with anorexia.
tion on infants also identified by neonatal screening demonstrated no These findings are associated with occasional skin abscess formation.
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anemia, and 6 of 23 infants were found to be polycythemic. The Patients with anorexia nervosa have no apparent bleeding diathe-
differences in these reports is not understood but may reflect, in part, sis. The platelet count is normal to slightly decreased, 233,236 and the
the differences in the pathophysiology of congenital hypothyroidism. in vitro platelet aggregation response to epinephrine, adenosine
The association between autoimmune thyroid disease and anemia diphosphate, and collagen is exaggerated. Coagulation defects are
is well recognized. The anemia may be exacerbated by several mecha- uncommon, except for those related to vitamin K deficiency reported
nisms, including iron deficiency, pernicious anemia, and AIHA. In in bulimia.
adults, the anemia of uncomplicated hypothyroidism is typically The hematologic changes in anorexia nervosa are directly corre-
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normocytic or macrocytic, with modest anisocytosis present on the lated with total body fat mass depletion. A bone marrow pattern
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peripheral smear. In children and adolescents, the same findings on magnetic resonance imaging suggestive of gelatinous transforma-
appear to be present. Additionally, children may have a decrease in tion of bone marrow (serous atrophy) is seen in patients with the
linear growth velocity as a manifestation of hypothyroidism, suggest- lowest hematologic parameters. Direct examination of the bone
ing that investigation of thyroid function is appropriate for children marrow reveals hypoplasia with loss of fat stores and replacement by
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with macrocytic anemia and declining growth rate. Pernicious a gelatinous acid mucopolysaccharide ground substance. Focal or
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anemia and iron deficiency may be less common in children with extensive necrosis may be present. Bone marrow histiocytes are
autoimmune thyroid disease than in adults. However, parietal cell relatively increased in number and have prominent blue-green gran-
antibodies are found in a significant percentage of children and ules. With nutritional supplementation, bone marrow hypoplasia
adolescents with autoimmune thyroid disease, a finding that may reverses, the gelatinous material disappears, and the hematologic
predispose them to the development of both iron deficiency and abnormalities, including neutrophil defects and low complement
pernicious anemia during young adulthood. 226 levels, resolve by 8 weeks.
Disturbances of hemostasis are also well recognized as a manifesta-
tion of thyroid dysfunction. Overt hypothyroidism and hyperthy-
roidism modify the hemostatic balance in opposite directions, with THROMBOEMBOLIC COMPLICATIONS
hypothyroid patients having an increased risk of bleeding and hyper- IN CHILDHOOD ILLNESS
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thyroid patients having an increased risk of thrombosis. There are
few reports of bleeding or thrombosis in children and adolescents Improvements in medical and surgical care, particularly advances in
attributed to uncomplicated overt thyroid dysfunction. Of interest is critical and supportive care, have led to increased survival among
the association between acquired von Willebrand disease and hypo- children with malignancy and chronic illnesses. However, the
thyroidism reported in several adolescent girls, which may be a cause extended survival of these children has led to comorbidities such as
of menorrhagia. 228–230 This hemostatic imbalance may improve with thromboembolic complications. The increased risk of thromboem-
thyroid hormone replacement. bolism in children with chronic illnesses is multifactorial and can
More global immune dysregulation syndrome may result in include the illness itself, medical and surgical interventions, or the
both endocrine dysfunction, including thyroid abnormalities, and central venous line used to administer therapy.