Page 2491 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 152 Hematologic Manifestations of Childhood Illness 2223

possibly associated with an increased bleeding risk, especially in those Findings of studies of neutrophil function in children with CF are
receiving aspirin. The multimer pattern reveals decreased large- conflicting. Some reports indicate impaired chemotaxis, chemilumi-
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molecular-weight multimers. Children with polycythemia have nescence, granule release, and superoxide production, 170–172 but others
contracted plasma volumes; therefore when blood samples are col- have demonstrated factors in patient sputum that actually enhance
lected, extra care should be taken to ensure the proper 1 : 9 ratio of neutrophil and monocyte responses to stimulants. 173,174 Although
3.8% sodium citrate to blood to prevent artificial abnormalities in these sputum factors may improve neutrophil killing ability, they also
coagulation test results. may worsen neutrophil-mediated lung damage through increased
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The etiology of the coagulation abnormalities in CCHD is release of neutrophil elastase. Evaluation of immune function has
unclear. Earlier reports suggesting a role for consumptive coagulopa- revealed impaired lymphoproliferative responses to Pseudomonas spp.
thy have not been confirmed. Protein C levels in 8 of 29 term infants and other gram-negative bacterial antigens, defective opsonization,
with CCHD were significantly lower than in control participants increased levels of circulating immune complexes, and decreased
with no evidence of familial deficiency. Of these infants, two had numbers of T-helper cells in 30% of patients. 152,176 The contribution
thrombotic complications, and four had consumptive coagulopa- of these findings to frequent pulmonary infection is still under
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thy. Platelets have shortened survival times (even with normal investigation.
counts), and normal to increased numbers of megakaryocytes in the Children with CF usually do not experience clinically significant
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bone marrow have been reported. This increased platelet destruc- bleeding owing to impaired hemostasis despite the risk of liver disease
tion does not appear to be attributable to DIC. Both the platelet and and vitamin K deficiency from malabsorption. An exception may be
coagulation abnormalities are directly proportional to the degree of infants younger than 1 year of age, in whom rare case reports of
hypoxemia and polycythemia. For example, whereas children with vitamin K–deficient hemorrhage have been reported in association
oxygen saturation greater than 60% have a mean platelet count of with CF. 177–179 Routine coagulation tests usually yield normal results,
315,000/µL, those with oxygen saturation less than 60% have a mean with an occasional prolonged PT reported. A study by Corrigan and
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count of 185,000/µL. The mild platelet and coagulation abnor- colleagues 156,180 revealed that 60% of 24 patients had a more subtle
malities usually are decreased or corrected after surgical repair of deficiency of prothrombin activity, thought to be caused by vitamin
the heart defect. 157,162 With bleeding or if surgery is not possible, the K deficiency. Other investigators, using direct measurement of
coagulopathy may be treated by correction of polycythemia to vitamin K and protein induced by vitamin K absence/antagonist-II
a hematocrit level of 60% by using slow plasma exchange (PIVKA-II), have reported conflicting percentages of patients to be
transfusion. 163 vitamin K deficient, 181,182 with another uncontrolled study demon-
strating normalization of PIVKA-II values in many patients by
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routine administration of daily oral vitamin K. Routine vitamin K
Cystic Fibrosis supplementation is recommended for all patients with CF, although
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there are inadequate data to define the ideal dose. 185
Cystic fibrosis (CF) is a multisystem disorder of exocrine gland dys- Children with CF appear to have a particularly high predisposi-
function characterized by chronic pulmonary disease, pancreatic tion to recurrent venous thrombosis. In one study of 19 patients with
exocrine insufficiency, hepatic dysfunction, abnormal reproductive recurrent venous thrombosis, 6 had CF, but none of 101 patients
organ function, and intestinal obstruction associated with abnormally with thrombosis without recurrence had CF. A striking association
high sweat electrolyte levels. It is an autosomal recessive disease with with respiratory tract colonization with Burkholderia cepacia was
an incidence of 1 in 2000 live births. noted, as was the frequent presence of a central venous catheter.
Severe hemolytic anemia caused by vitamin E deficiency may be Several of the recurrences occurred while patients were on therapeutic
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186
the presenting manifestation of CF. Dolan initially linked defi- anticoagulation. Studies of small populations of both children and
ciency of vitamin E with severe hemolytic anemia in infants who adults have documented an increased incidence of protein C and
presented with pallor, edema, hypoproteinemia, and thrombocytosis. protein S deficiency, as well as lupus anticoagulants. 187–189 These
This complication can be seen as early as 6 weeks of age. abnormalities are likely acquired defects in most patients with CF
Many children with CF are chronically hypoxic, yet they do because of the potential for having subclinical vitamin K deficiency,
not have the expected augmented erythroid response. In a study liver function abnormalities, and recurrent infections. Follow-up
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by Vichinsky and colleagues, none of 42 children with CF had studies have not shown persistent abnormalities in many patients.
polycythemia, and 30% (especially the boys and the older children) The incidence of activated protein C resistance and factor V Leiden
had a normochromic, normocytic, or hypochromic microcytic was similar to that in the general population. Although it would be
anemia with reticulocytopenia. In contrast with children with anticipated there would be an increased frequency of venous throm-
CCHD, there was no appropriate increase in RBC 2,3-DPG levels, bosis because of the increased use of central venous catheters, at least
no right shift of the oxyhemoglobin curve, and either a low or a one large study of older adolescents and adults with CF who had
normal erythropoietin level. In vitro assays showed normal erythroid totally implanted venous access devices revealed a very low incidence
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progenitor cell numbers and no serum inhibitor of erythropoiesis. of complications. Whether patients with CF have a greater risk of
Up to 66% of the children studied had abnormalities consistent venous thrombosis than the control population awaits a larger pro-
with iron deficiency, and all responded to oral or parenteral iron spective controlled trial.
therapy.
It appears that the etiology of anemia in CF is multifactorial. A
blunted erythropoietic response to hypoxia plus iron deficiency sec- HEMATOLOGIC MANIFESTATIONS OF
ondary to iron malabsorption or poor dietary iron intake may each
be partially responsible for the development of anemia. If iron defi- CHILDHOOD GASTROINTESTINAL DISEASE
ciency persists despite adequate oral supplementation, the possibility
of ongoing blood loss or of iron malabsorption that may necessitate Milk Protein–Induced Enteropathy
parenteral iron replacement should be considered. Soluble transferrin and Heiner Syndrome
receptor levels may be helpful in distinguishing iron deficiency from
anemia of chronic inflammation in CF because, unlike serum ferritin The association of iron deficiency with dietary intake of cow’s milk
and transferrin, soluble transferrin receptor does not appear to be an in young infants is established. A major contributing factor is the rela-
acute-phase reactant. 166,167 tively poor bioavailability of iron in cow’s milk compared with breast
Use of multiple antibiotics in patients with CF is routine. There milk. In addition, the rapid growth of infants and corresponding rapid
have been a number of case reports of adult patients with severe, increase in RBC mass necessitate an increased requirement for dietary
life-threatening hemolytic anemia attributed to piperacillin. 168,169 iron. The role of cow’s milk in inducing occult GI blood loss in infants
This complication has not been reported in children to date. was carefully documented more than three decades ago in a sentinel