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598 Part V Red Blood Cells

been the standard of care for children with fevers higher than 38.5°C. flow, RBC adherence, and hypoxia; but in addition, it has been
Prompt attention to fever can reduce the risk of severe pneumococcal speculated that depletion of NO by the free Hb released through
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sepsis. Rapid administration of antibiotics has resulted in a lower intravascular hemolysis may also play a role. The age-specific
incidence of meningitis among patients with bacteremia than 20 pattern of stroke risk in SCD may be related to the higher cerebral
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years ago when the incidence was 50%. The efficacy of ceftriaxone flow rates in early childhood. Cerebral thrombosis, which accounts
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therapy for S. pneumoniae and H. influenzae infection has led to for 70% to 80% of all CVAs in patients with SCD, results from
new treatment algorithms that recommend outpatient therapy for large-vessel occlusion (see Fig. 42.9) rather than the more typical
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most patients. However, resistant S. pneumoniae have emerged, neces- microvascular occlusion of SCD. Silent infarcts are thought to
sitating a thorough knowledge of local resistance patterns to guide result from microvascular vasoocclusion or thrombosis or chronic
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the choice of alternate antibiotics (particularly vancomycin, to which hypoxia in the periphery stemming from large-vessel disease.
resistance has not been observed). In 30% of patients with SCD, major vessel stenosis results in the
Please see Pulmonary Complications for further discussions formation of friable collateral vessels that appear as puffs of smoke
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regarding pneumonia and acute chest syndrome. (moyamoya in Japanese) on angiography. Moyamoya disease predis-
poses to thrombotic and hemorrhagic strokes, seizures, and cognitive
Meningitis disability. 167
Meningitis therapy should cover S. pneumoniae and probably H. The relative risk for stroke is 200–400 times higher in chil-
influenzae type b and should be continued for at least 2 weeks. dren with SCD compared with the children without SCD. The
prevalence of clinically overt stroke is 11%. Clinically silent infarc-
Salmonella and Osteomyelitis tion detectable by MRI affects 17% to 20% of patients by age 20
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In this patient population, osteomyelitis is commonly caused by years. Silent infarcts are associated with cognitive impairment.
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Salmonella spp. Staphylococcus aureus, the most common etiology Even in patients without silent or overt cerebral infarction, cogni-
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in patients without SCD, accounts for less than 25% of SCD cases. tive functioning can be impaired. Almost 50% of the children
Infection usually affects long bones, often at multiple sites. with “silent” infarcts eventually require lifelong support or custodial
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The diagnosis is confirmed by culture of blood or infected bone. care because of neuropsychologic deficits. Whereas infarctive
Parenteral antibiotics that cover Salmonella spp. and S. aureus are strokes were common in children and those older than 30 years of
given, and antibiotic therapy is based on culture results. Parenteral age, hemorrhagic stroke was most common between ages 20 and
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antibiotics are continued for 2–6 weeks. Surgical drainage or 30 years. 23
sequestrectomy may be required. Most patients are cured by this Sickle cell–specific risk factors for CVA include increased cerebral
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approach, but there may be recurrences. 156 blood flow velocity (discussed further under Primary Prevention of
Articular infection is less common and is often caused by S. Cerebrovascular Accidents), a history of overt or silent cerebral infarc-
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pneumoniae. 156 tion, nocturnal hypoxemia, more severe anemia, higher reticu-
locyte counts, lower Hb F levels, higher WBC counts, the Hb SS
Parvovirus B19 genotype (rather than Hb SC disease or sickle cell–β-thalassemia),
The specificity of the parvovirus B19 (see also Aplastic Crisis) for nocturnal hypoxemia or sleep apnea, migraines, elevated homocyste-
erythroid precursor cells, coupled with the accelerated erythropoiesis ine levels, “relative” systolic hypertension (i.e., those at the high end
in hemolytic anemias, leaves sickle cell patients vulnerable to infec- of the lower-than-normal range characteristic of SCD). 23,174 Genetic
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tion by this agent. In SCD, parvovirus infection is a common cause markers of increased risk are the Central African Republic (CAR)
of aplastic crisis, especially in children. It has been reported to cause haplotype and the absence of α-thalassemia. 163,175 Both small- and
bone marrow necrosis, acute chest syndrome, pulmonary fat embo- large-vessel thrombosis can occur. Specific HLA alleles separately
lism, hepatic sequestration, and glomerulonephritis. 135–138 correlate with small- versus large-vessel stroke risk, suggesting that
different pathologic processes may be involved. 163
Urinary Tract Infections In addition to these sickle cell–specific predictors of stroke, one
Patients with SCD are at a higher risk for urinary tract infections and must also consider the well-documented modifiable risk factors for
pyelonephritis than the general population. Escherichia coli is the stroke that are operational in the general population; these are
most common uropathogen and can cause septicemia in these hypertension, exposure to cigarette smoke (active smoking or passive
patients. Persistent urinary tract infections may be secondary to renal exposure), diabetes, atrial fibrillation, dyslipidemia, carotid artery
papillary necrosis. All urinary tract infections in this patient popula- stenosis, postmenopausal hormone therapy, poor diet, physical
tion should be considered complicated, requiring 10–21 days of inactivity, obesity, and fat distribution. Less well-documented but
appropriate antibiotic therapy. potentially modifiable risk factors include alcohol or drug use, oral
contraceptive use, and sleep-disordered breathing. 168
CVAs are heralded by focal seizures in 10% to 33% of cases
Neurologic Complications and by TIAs in 10%. CVAs are fatal in approximately 20% of
initial cases, recur within 3 years in nearly 70%, and are the cause
Neurologic complications occur in 25% or more of patients with of motor and cognitive impairment in the majority. Intracranial
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SCD. Neurologic complications include CVAs (consisting of hemorrhage results in the same signs as thrombosis, but in addition,
transient ischemic attacks [TIAs], overt and silent cerebral infarction, neck stiffness, photophobia, severe headache, vomiting, and altered
cerebral hemorrhage), seizures (which can be a presenting feature of consciousness may occur. Coma suggests hemorrhage rather than
CVA), unexplained coma, spinal cord infarction or compression, thrombosis. A typical presentation is coma and seizures without
central nervous system infections, vestibular dysfunction, and sensory hemiparesis. Although the mortality rate may be as high as 50%,
hearing loss. 159 the morbidity of survivors is low. Hemorrhage may be subarachnoid,
intraparenchymal, or intraventricular, which can be differentiated by
Cerebrovascular Accidents, Pathophysiology, Incidence, angiography. The favorable neurosurgical outcome in subarachnoid
Risk Factors, and Presentation 160 hemorrhage caused by ruptured aneurysm justifies an aggres-
Histopathologic evaluation of large-vessel involvement in SCD shows sive approach to diagnosis, transfusion, vasodilatory therapy, and
a pattern of smooth muscle proliferation with overlying endothelial surgery.
damage and fibrosis. Smaller arterioles and capillaries demonstrate
distension, thrombosis, and vessel-wall necrosis. 161,162 Aneurysmal Primary Prevention of Cerebrovascular Accidents
dilation associated with hemorrhagic stroke occurs at regions of The overall risk of stroke in pediatric patients with SCD is 1% per
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intimal hyperplasia. The vessel wall changes are likely multifacto- year; however, in the subset of patients with transcranial Doppler,
rial in origin related to endothelial injury from high and turbulent evidence of a high (>200 cm/s) cerebral blood flow velocity in the