Treatment Options for Painful Crises
The most beneficial new treatment for painful crisis in the past two decades has been the use of hydroxyurea. After early studies showed promise, a phase III clinical trial in adults with SCD who suffered frequent painful crises (i.e., more than four per year) and who were given doses of up to 35 mg/kg/day of hydroxyurea showed a dramatic decrease in painful episodes. These patients also endured fewer episodes of acute chest syndrome, with a relative risk of 0.44, and experienced a reduced need for transfusions, with a relative risk of 0.64. This trial was stopped early (at 21 months average follow-up) due to the striking findings.8 Subsequent longer-term trials have not shown any of the feared theoretical complications of hydroxyurea, including cytopenias (when the production of one or more blood cell types ceases or is greatly reduced) or secondary malignancies.9 (See Table 3, p. 40.)
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Childhood Complications
Some SCD complications are more prominent or more severe in early childhood than in adulthood. Two examples of this phenomenon are infectious complications and splenic sequestration. Pediatricians and parents of children with SCD live in fear of febrile illness because overwhelming infections such as pneumococcal sepsis remain the primary reason for death in children with SCD. This was especially true before Hemophilus influenza type b (Hib) and pneumococcal conjugate vaccines were introduced and before penicillin prophylaxis from birth through age five became universal.
Though functionally asplenic, adult patients are at a relatively low risk for overwhelming infections because their immune systems have matured enough to allow type-specific antibody production to polysaccharide antigens.7 Still, adults with SCD should be aggressively evaluated for infectious etiology of any febrile illness and routinely administered empiric antibiotics to cover strep species.
Splenic sequestration occurs when sickled cells are caught up in the spleen; this causes massive hemolysis, splenic enlargement, and cardiovascular compromise, and it is most common in SCD patients younger than five. Thankfully, this is rare in adults with SS and SB0Thal; however, the notable exception to this rule is in patients with hemoglobin SC disease or SB+Thal, where complete splenic infarction does not routinely occur.
Acute chest syndrome (ACS) is perhaps the most feared complication in both children and adults with SCD—and with good reason. It is the second most common cause for hospital admission in SCD patients, and it is an independent risk factor for death in SCD.7,10 Occurring more often in children, ACS is typically more severe in adults, in whom ACS can progress rapidly to an acute respiratory distress syndrome (ARDS)-like picture, with mortality reaching 5%-9%.11
ACS involves a classic triad of fever, chest pain, and new pulmonary infiltrates on chest X-ray, but patients are invariably hypoxic and dyspneic as well. The etiology of ACS varies. In one series, 54% of patients had an identified infectious pathogen, most commonly chlamydia or mycoplasma. Bronchoalveolar lavage (BAL) showed lipid-laden macrophages in about 16%, suggesting fat embolism after bony infarcts. The remainder of patients were presumed to have primary pulmonary infarctions.11 The treatment of ACS involves broad-spectrum antibiotics, especially atypical coverage, along with transfusion (simple versus exchange), supplemental oxygen, pain control, and judicious use of IV fluids.
The second most feared complication in SCD is stroke, which can be devastating in both children and young adults. Eleven percent of patients younger than 20 have ischemic strokes, with a risk of stroke that is 200 times higher than that of age-matched peers.9,12 The peak incidence of ischemic stroke occurs before 10 and after 30. These patients are also susceptible to hemorrhagic strokes, the incidence of which peaks in the third decade, for reasons that are unclear.13