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Chapter 42 Sickle Cell Disease 589

TABLE Baseline Evaluations to Consider TABLE Disease-Modifying Treatments to Consider a
42.2 42.3
Tests Robust clinical Penicillin prophylaxis
data Streptococcus pneumoniae vaccination
Blood tests CBC with differential Hydroxyurea
Reticulocyte count Chronic exchange transfusion
Hemoglobin HPLC or electrophoresis Iron chelation for chronic iron overload b
LDH Limited Daily multivitamin without iron or Folate
Renal function tests clinical data supplementation AND vitamin D replacement c
Liver function tests Haemophilus influenzae vaccination
Mineral panel Influenza vaccination
Serum iron, ferritin, TIBC Erythropoietin
Vitamin D level Phlebotomy
Hepatitis B sAg
Hepatitis C antibody Experimental Hb F reactivation with decitabine, histone
RBC alloantibody screen deacetylase inhibitors, or imids
RBC typing Erythropoietin for chronic relative reticulocytopenia
D-dimer a Nutritional supplements and antioxidants (e.g.,
C-reactive protein a glutamine, zinc, multivitamins)
Brain natriuretic peptide N-acetylcysteine
Urine and kidney tests Urinalysis a b See text for specific indications and limitations.
Renal ultrasonography b c Best data from thalassemia patient experience.
Risks minimal therefore, it is generally done.
c
Radiology MRI or MRA brain (adults) or transcranial Hb F, Fetal hemoglobin.
Doppler ultrasonography starting at age
2 years (children)
Chest radiography d
Hip or shoulder radiograph or MRI (or placebo-controlled study, the PROPS II study concluded that it is
both) c safe to stop prophylactic penicillin therapy at age 5 years in children
Bone density in teenagers and adults who have not had prior severe pneumococcal infection or splenec-
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Cardiology and pulmonary Echocardiogram tomy and are receiving regular follow-up care. However, the power
of the study was restricted by the limited number of S. pneumoniae
Neurocognitive Neurocognitive testing d
systemic infection events. In an analysis of a patient population
a Consider following as surrogate markers after initiation of disease-modifying receiving penicillin prophylaxis and the Pneumovax, the rate of severe
intervention. S. pneumoniae infections was 2.4 per 100 patient-years. This was
b If hematuria with red blood cells in urine.
c As clinically indicated. favorable compared with the historic prepenicillin prophylaxis rate of
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d If the patient has poor school performance, an abnormal memory, or abnormal 3.2–6.9 per 100 patient-years. These measures reduce risk but do
MRI findings. not remove it. The risk of recurrent S. pneumoniae sepsis and death
CBC, Complete blood count; HPLC, high performance liquid chromatography; in patients who have had previous sepsis is much increased; all
LDH, lactate dehydrogenase; MRA, magnetic resonance angiography; MRI,
magnetic resonance imaging; RBC, red blood cell; sAg, surface antigen; TIBC, patients having a history of pneumococcal sepsis should remain on
total iron-binding capacity. penicillin prophylaxis indefinitely and are not candidates for outpa-
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tient management of febrile episodes. Parents must be aggressively
counseled to seek medical attention for all febrile events.
and penicillin prophylaxis do not directly affect the sickling process
or vasculopathy, they have had an impact on survival and therefore Hydroxyurea and Fetal Hemoglobin Reactivation
are included under the umbrella of disease-modifying therapies.
Therapeutic options are further discussed in the sections describ- The level of Hb F in erythrocytes plays a critical role in determining
ing organ-specific complications. patient outcomes. Individuals who have SCD and another condition
called HPFH have 70% Hb S in their RBCs but are neither anemic
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nor symptomatic. The uniform distribution of Hb F among their
Vaccination and Penicillin Prophylaxis RBCs interferes with Hb S polymerization, increases its solubility,
and prevents RBC sickling. 41,42 Even at lower levels of Hb F seen in
Children should be immunized against S. pneumoniae, Haemophilus patients without HPFH, crisis rate and mortality are inversely pro-
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influenzae, hepatitis B, and influenza. Vaccination and penicillin portional to Hb F level. 19–22 These findings prompted the idea that
prophylaxis can reduce the risk of serious pneumococcal infections. 9,36 pharmacologic reactivation of Hb F production might be of benefit
Vaccination schedules recommend inoculation with heptavalent to patients.
pneumococcal conjugated vaccine at 2 months followed by two more HU is an inhibitor of ribonucleotide reductase and a cytotoxic
doses 6–8 weeks apart (primary series) and a booster at 12 months. agent that can elevate Hb F levels via an unknown pathway. A
This is followed by Pneumovax at age 2 and 5 years. In adults, the double-blind, placebo-controlled, intention-to-treat multicenter
Pneumovax should be readministered every 5 years (http:// study of HU as treatment of pain crisis in SCD found that HU
www.cdc.gov/vaccines/pubs/vis/default.htm). produced definite hematologic changes. HU was started at 0.15 mg/
For children younger than age 5 years, prophylactic penicillin kg/day and escalated to 0.30 mg/kg/day as tolerated and to maintain
9
−1
recommendations are 125 mg penicillin V orally twice daily until age an absolute neutrophil count no lower than 2000 × 10 L . There
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2–3 years and 250 mg thereafter. Penicillin prophylaxis begins at 2 were significant increases in the levels of Hb, Hb F, F cells, F reticu-
months. Randomized, double-blind, placebo-controlled studies of locytes, packed cell volume (PCV), and MCV and declines in the
prophylactic penicillin beginning in infancy, including the prophy- mean level of leukocytes, polymorphonuclear leukocytes, reticulo-
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lactic penicillin or placebo study (PROPS), have found that this cytes, and dense sickle cells (Table 42.4). The significant clinical
therapy reduced the incidence of S. pneumoniae bacteremia by 84% changes were decreased rate of acute painful episodes, longer interval
in children younger than 3 years. 9,36 A randomized, double-blind, to first and second acute painful episode, fewer episodes of acute chest