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Chapter 42 Sickle Cell Disease 587

A B C D

Fig. 42.6 THE SPLEEN IN SICKLE CELL DISEASE. Histologic section (A) of the splenic red pulp shows
engorgement of the splenic cords with sickled cells. In infants, excessive pooling in cords can lead to a splenic
sequestration crisis. Later in life, the spleen undergoes autoinfarction. The gross pathology (B) shows a tiny
4.5-cm spleen with rough external surface caused by scarring from repeated infarcts. Histologic section reveals
classic Gamna-Gandy bodies (C and D) also caused by repeated infarction. These are composed of hemosiderin-
laden macrophages, calcium deposits, and foreign body giant cells.

A B C
1.0 Black females 1.0 1.0
0.9 0.9 Females 0.9 Hb F >8.6%
with SC
0.8 Black males 0.8 0.8
Probability of survival 0.6 Females with SS Probability of survival 0.5 Males with SC Probability of survival 0.6 Hb F <8.6%
0.7
0.7
0.7
0.6
0.5
0.5
0.4
Males with SS
0.4
0.4
0.3
0.3
0.2 0.2 0.3
0.2
0.1 0.1 0.1
0.0 0.0 0.0
0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70
Age (yr) Age (yr) Age (yr)
Fig. 42.7 Life expectancy in patients with sickle cell disease for patients with Hb SS disease (A), Hb SC
disease (B), and with different levels of fetal hemoglobin (Hb F) (C). (From Platt OS, Brambilla DJ, Rosse WF,
et al: Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 330:1639, 1994.)

Life expectancy is decreased, although in the past 30 years, this Hb F levels and the coinheritance of an α-thalassemia trait have
15
has dramatically improved for patients in the West: in 1973, Diggs been identified as favorable disease modifiers in multiple studies
16
reported that the mean survival was 14.3 years; in 1994, Platt et al (Table 42.1). 20–22 The level of chronic anemia (which is influenced
reported that life expectancy was 42 years for men and 48 years for by the presence of an α-thalassemia trait and by Hb F levels) is
women with sickle cell anemia (Fig. 42.7). This improvement in of considerable predictive value. Patients with more severe anemia
23
survival is most likely the result of improved general medical care, are more likely to develop infarctive and hemorrhagic stroke, to
including prophylactic penicillin therapy and vaccination against S. have glomerular dysfunction, 24,25 and perhaps to give birth to low-
9
pneumoniae. These survival profiles are likely to be relevant even birthweight babies. 26,27 Conversely, they have fewer episodes of acute
28
28
today, although a cohort of patients followed since 1975 show chest syndrome and (after age 20 years) a lower mortality rate.
improvement in the probability of survival to age 20 years compared Progressive anemia from renal endocrine deficiency or a decrease in
17
with patients born before 1975 (89% versus 79%). The poor sur- bone marrow function from vasoocclusion is associated with early
vival and litany of chronic organ damage in survivors emphasize the death. 18,19
17
need for disease-modifying interventions to prevent vasculopathy. A number of other genetic polymorphisms may be relevant to
There are some indications that disease-modifying agents such as disease severity, for example, with regards to the risk of stroke.
hydroxyurea (HU) can improve survival. 18,19 However, most of these markers are not widely used to guide decision
making. 21
Predictors of Disease Severity
Principles of Management
The ability to predict clinical course would allow more rational tailor-
ing of therapy to individual patients (e.g., selection of patients for The twin pillars of therapy are disease modification (prevention of
high-risk but effective options such as stem cell transplant). Higher crises, complications, chronic organ damage, and early mortality)