Page 2501 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 152 Hematologic Manifestations of Childhood Illness 2233

associated with the use of TAC. 312,384 Hemophagocytic syndrome has metoclopramide, and nitroethane (an artificial fingernail remover).
also been reported in the posttransplant setting, usually caused by an Although the list of oxidants reported to cause methemoglobinemia
acquired viral infection. 385 is long, methemoglobinemia caused by exogenous agents is uncom-
monly seen in infants and children. 393
HEMATOLOGIC ASPECTS OF POISONING
Lead Poisoning
It has been estimated that about 6 million children, most younger
than 5 years of age, ingest some toxin each year. The effects of toxins Lead poisoning in children has been a serious public health problem
on the blood are diverse, usually nonspecific, and in most situations for decades. However, the most serious toxic effects of lead (e.g.,
overshadowed by the nonhematologic manifestations of the expo- encephalopathy) commonly seen in the past are rarely encountered
386
sure. With certain toxins, however, bleeding, anemia, or change in today, primarily because of measures instituted to decrease lead
the appearance (color) of the blood may be an important component exposure (e.g., no-lead paint, no-lead gasoline) and screening pro-
of the clinical sequelae of an acute exposure. grams in high-risk areas. Mean blood lead levels in the United States
The abnormalities of hemostasis after poisoning are numerous, have declined, from 15 µg/dL between 1976 and 1982 to 3.6 µg/dL
383
and the mechanisms vary. Bleeding may be the only manifestation of between 1988 and 1991. Nonetheless, lead toxicity remains a
warfarin toxicity secondary to an overdose of the drug or ingestion problem, especially in high-risk children. In 2010, 6% of impover-
of a rodenticide containing warfarin. Any hepatotoxic substance (e.g., ished children aged 1 to 2 years were found to have lead levels above
394
iron, acetaminophen) may lead to decreased synthesis of clotting the upper reference range. Additionally, children arriving from
factors and resultant coagulopathy. Bleeding in these circumstances other countries with less stringent public health requirements regard-
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is delayed for at least 24 hours, although there appears to be an early ing lead exposure remain at risk for significant lead toxicity.
coagulopathy in iron poisoning that may be caused by a direct effect Increasing evidence shows that even low levels of lead exposure are
387
on clotting protein function and not hepatotoxicity. DIC has been associated with a significant decline in neurodevelopmental outcome,
seen after ingestion of mushrooms of the Amanita genus or after a and in 1991, the CDC lowered the intervention level of lead in the
bite from the brown recluse spider (Loxosceles reclusa). Poisonous blood from 25 to 10 µg/dL. 395,396 Reviews of the public health issues
snake bites can result in coagulation abnormalities characterized by relating to lead poisoning in children have been published. 397
hypofibrinogenemia with or without thrombocytopenia or a DIC- The occurrence of lead poisoning in children with sickle cell
386
like syndrome. Severe thrombocytopenia has been described with disease may be underrecognized. Pica may be a manifestation of sickle
elemental mercury poisoning. cell anemia, even in the absence of iron deficiency, predisposing
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Acute hemolytic anemia may be the presenting manifestation after children to lead ingestion. Additionally, some children with sickle
exposure to drugs and toxins in children with G6PD deficiency or cell disease may be at risk for environmental lead exposure, including
hemoglobin Zürich or (rarely) in otherwise healthy children. Severe substandard housing with lead paint. The signs and symptoms of lead
hemolytic anemia has been seen after the bite of the brown recluse toxicity may resemble those of sickle cell disease, including abdominal
spider and of a rattlesnake and after a wasp sting. pain, peripheral neuropathy with extremity pain, constipation, and
399
Exposure to certain toxins may result in characteristic color hyponatremia. Lead toxicity should be considered in the differential
changes of the blood, which in turn may be reflected clinically in diagnosis of children with unusual manifestations of sickle cell disease.
abnormal skin color. The child with methemoglobinemia (see next The primary hematologic effect of lead is interference at multiple
paragraph) presents with a slate-gray cyanosis unresponsive to 100% points along the heme synthetic pathway. The two most important
oxygen administration. On exposure to air, the blood retains a distinct effects are inhibition of δ-aminolevulinic acid dehydratase and fer-
brown color. Patients with toxic exposure to carbon monoxide or rochelatase, resulting in the accumulation of heme intermediates such
cyanide have increased levels of carboxyhemoglobin or cyanhemoglo- as protoporphyrin. A shortened RBC survival time accompanies lead
bin, respectively, resulting in a cherry-red color of the blood and skin, poisoning and probably is caused by decreased activity of pyrimidine
but only with high concentrations of the offending hemoglobin. 5-nucleotidase (also resulting in basophilic stippling of the RBC) and
Infants (up to 4 months of age) are at particular risk for developing possibly inhibition of G6PD and the pentose shunt. 400
methemoglobinemia because of a reduced amount (approximately The anemia of lead poisoning has classically been described as a
60% of normal) of cytochrome b5 reductase present in neonatal hypochromic, microcytic anemia, as might be expected from the
RBCs. Methemoglobinemia has been described in infants with diar- effects of lead on heme synthesis. Although anemia has been said to
rheal illness and in infants exposed to exogenous agents. 388 be a common finding in lead intoxication, in reality, anemia is
389
Yano and colleagues described 11 patients with transient met- uncommon unless the lead poisoning is severe or there is associated
hemoglobinemia, all infants younger than 1 month of age who pre- iron deficiency.
sented with vomiting, diarrhea, and acidosis. In prospective studies A strong association exists between lead poisoning and iron
of infants younger than 6 months of age with diarrheal disease, 64% deficiency in children. Both tend to occur in the same population of
had elevated levels of methemoglobin (with a mean ± SD of 10.5% predominantly lower socioeconomic status. Experimentally, iron
± 12.3%); 31% were cyanotic; most infants were small or failing to deficiency has been shown to increase lead absorption, retention in
thrive; there was no association of methemoglobinemia and acidosis; tissues, and toxicity. Iron deficiency also decreases lead excretion
401
and all children recovered from their illness. 390,391 Although most during chelation. Lead may impede iron absorption and metabo-
infants with endogenous methemoglobinemia can be managed with lism, leading to a vicious circle of increasing lead toxicity and worsen-
support and hydration, treatment with methylene blue (1 mg/kg) is ing iron deficiency. In a study of children with lead poisoning (blood
indicated in symptomatic or more severely affected children (i.e., lead ≥30 µg/dL), 86% were found to have iron deficiency, and 100%
with methemoglobin >20%–30%). of those with more severe lead poisoning (CDC risk class III) were
Nursery epidemics of methemoglobinemia have been reported in iron deficient. 402
normal newborns exposed to disinfectants or aniline dyes used to A number of reports of children with lead toxicity have docu-
mark diapers. Infants fed formulas made with well water containing mented the infrequent occurrence of anemia without concomitant
402
a high concentration of nitrates have developed methemoglobinemia. iron deficiency. Cohen and colleagues found anemia in 12% and
EMLA cream (Akorn Pharmaceuticals, Lake Forest, IL), a eutectic microcytosis in 21% of iron-sufficient children with severe lead
mixture of the local anesthetics lidocaine and prilocaine, has been poisoning (CDC risk classes III and IV). The combination of anemia
effective in decreasing pain in infants undergoing circumcision. plus microcytosis, however, was found in only one of the 58 children
403
Methemoglobinemia has been reported with EMLA use in this situ- in their series. Yip and associates found a 30% incidence of anemia
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ation, but only in overdose. Other ingestions associated with in less severely affected children (CDC classes I to III), but of those
methemoglobinemia include phenazopyridine (Pyridium), dapsone, with either mild or no iron deficiency, only 6% were anemic. Clark