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772 Part VI: The Erythrocyte Chapter 49: Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities 773

patients and two-thirds will have infants with birth weights less than the H. influenzae and hepatitis B virus should be given. Influenza virus vac-
50th percentile. 294,295 There is an increased frequency of VOEs reported cine should be given annually because viral respiratory infection favors
during pregnancy. In a study looking at pregnancy outcomes in SCD invasive bacterial infection.
patients compared to non-SCD patients with comorbidities, patients Parents and caregivers of children should be educated to rec-
with SCD displayed a significantly increased incidence of venous ognize infections and to seek medical attention early. Diagnosis of
thromboembolism (VTE), nonhemorrhagic obstetric shock (defined established infections varies by site and offending agent. For invasive
as pulmonary thromboembolism, amniotic fluid embolism, acute uter- pneumococcal disease, ceftriaxone remains the drug of choice despite
ine inversion, and sepsis), and infection, despite being significantly concerns of immune-mediated hemolysis. Infections seen classically in
younger. 296,297 Other studies have shown similar findings, especially the SCD patients include salmonella osteomyelitis and penumonia caused
fivefold increased risk of VTE in this population. 295,297,298 by atypical bacteria like Chlamydia and M. pneumoniae, which need to
Given increased risk of preeclampsia and eclampsia, patients be treated with the appropriate antibiotics.
should have close monitoring of blood pressure and proteinuria after 20 The spectrum of infectious complications in adults may be differ-
302
weeks of gestation. Fetal nonstress and umbilical artery Doppler stud- ent. One study reported data on blood infections in adults. Pneumo-
ies should be undertaken after 28 weeks to identify patients who might coccal infections were rare. S. aureus was the predominant organism.
benefit from early delivery. Studies examining prophylactic red cell Patients with S. aureus had a predilection for bone-joint infection. Those
transfusions in pregnancy have shown mixed results. Patients should be with indwelling venous catheters and a severe disease course appeared
transfused to a Hb concentration of less than 6 g/dL, because abnormal to have a high risk for bloodstream infections.
fetal oxygenation and death have been reported below this Hb level in Although the sickle trait confers resistance to malaria, protection
non-SCD populations. Otherwise, patients should be transfused based is not complete and severe disease and deaths from malaria have been
294
on guidelines for the nonpregnant patient with SCD. Based on data reported in SCD patients. Malaria chemoprophylaxis is recommended
from animal models and small reports of spontaneous abortion or fetal for all patients living in or traveling to endemic regions. 318,319
death, the use of hydroxyurea is not recommended during pregnancy
and breastfeeding. 299,300 Hydroxyurea may decrease spermatogenesis Management during Anesthesia and Surgery
and therefore male patients may need to stop the drug temporarily Patients with SCD should have careful monitoring of Hb concentration,
when their partners are trying to conceive. Narcotics administered for hydration, oxygen, and metabolic studies in the perioperative period.
relief of pain have not been shown to cause fetal harm, but babies of Acute chest syndrome and VOE occur with higher frequency in the
mothers exposed to narcotics during pregnancy should be monitored perioperative period. Increased age is associated with increased com-
for the neonatal abstinence syndrome. 294 plications. 320–322 Transfusion to keep Hb levels approximately 10 g/dL is
Despite increased concern for VTE, given insufficient data, contra- recommended. Although a prior randomized trial showed no benefit
ception advice is similar as for women without SCD. 301 in decreasing SCD-related complications between patients transfused
aggressively to a mean HbS of less than 30 percent versus those trans-
Management of and Prevention of Infection fused to a total Hb of 10 g/dL with mean HbS percent of 59, more recent
Patients with SCD are predisposed to infections for a variety of reasons, data show reduction in clinically important events, especially serious
including functional asplenia and defective neutrophil responses. 302–306 complications, in the preoperative transfused group prior to low and
The magnitude of this problem was highlighted in 1971 in a landmark moderate risk surgery. 202,323 Care should be taken to avoid transfu-
306
paper by E. Barrett-Connor. Functional asplenia results in suscepti- sion-induced hyperviscosity.
bility to encapsulated microorganisms, particularly to S. pneumoniae,
especially in children younger than 5 years of age. The CSSCD data
reported an eight-per-100-patient-years rate of invasive bacterial infec- MODIFIERS OF DISEASE SEVERITY
tion in children younger than 3 years of age. 307 Some patients have a mild course with few problems related to SCD, and
Given the high incidence of infection, especially in childhood, survive into the sixth or seventh decade. In contrast, some patients have
infection prevention and rapid diagnosis of established infections is of a difficult course with multiple complications, frequent hospitalizations,
paramount importance. 308,309 The pneumococcal vaccine (PCV7) can be severe organ damage, and a significantly shortened life expectancy. 324,325
administered in infancy with effective immunologic response prior to Inheritance of α-thalassemia trait and a high HbF are two factors that
2 years of age; the American Academy of Pediatrics recommends it be ameliorate many complications of SCD. Genome-wide association stud-
administered at ages 2, 4, 6, 8, and 12 to 15 months. The PCV7 vaccine ies revealed three major loci associated with HbF levels: The β-globin
decreases invasive pneumococcal disease by as much as 80 to 90 per- locus on chromosome 11, an intergenic region between HBSIL and MYB
310
cent. The pneumococcal polysaccharide vaccine, PPV23, covers more genes on chromosome 6, and the BCL11 gene on chromosome 2.
326
serotypes but is not immunogenic prior to 24 months and response lasts Repression of BCL11A results in increased γ-globin gene expression and,
for 3 years. The first dose is recommended at 24 months with additional consequently, in increased HbF. The exact mechanism of how BCL11A
doses 3 to 5 years later. 309,311–314 Nonvaccine covered strains of S. pneumo- silences γ-globin expression is unclear; its expression seems to be con-
niae are emerging as important pathogens; therefore, prompt referral of trolled by an erythroid specific transcription factor, KLF1 with decreased
patients with suspected infection to a healthcare facility is important. 315 expression of BCL11A upon knockdown of KLF1 gene transcript. 326,327
Oral penicillin prophylaxis is recommended at a dose of 125 mg Inheritance of α-thalassemia and HbF level do not account for all
twice a day for children between 0 and 3 years of age and at 250 mg of the clinical diversity of SCD. The completion of the human genome
316
twice a day for children between 3 and 5 years of age. Penicillin pro- project has provided the impetus to study polymorphisms in candidate
phylaxis beyond 5 years is recommended only for patients with recur- genes as potential modifiers of disease severity. Association of poly-
rent pneumococcal infections or who have had surgical splenectomy. morphisms in candidate genes and different features of SCD such as
Patients allergic to penicillin are offered erythromycin. stroke, 328–330 ACS, bilirubin levels and cholelithiasis, 332–335 avascular
331
The meningococcal vaccine covers most invasive isolates of necrosis, priapism, and leg ulcers, as well as HbF levels, 337–342 and
336
253
245
N. meningitidis and is recommended by the American Academy of HbF response to hydroxyurea, have been studied in different groups
343
Pediatrics. Standard pediatric immunizations protecting against of patients.
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