Page 1296 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 96: Sickle Cell Disease 903

Complications of sickle cell disease
Chronic complications Acute complications
Retinopathy Stroke, meningitis
Post-hyphema
glaucoma, retinal
Anemia, leukocytosis
Obstructive sleep apnea infarction
Pulmonary hypertension Acute
Indirect Chest
hyperbilirubinemia Syndrome
Cardiomegaly
Isosthenuria, Sickle
chronic Functional hepatopathy
renal failure asplenia

Splenic sequestration,
splenic infarction
Papillary
necrosis
Avascular
necrosis Cholelithiasis
Delayed Priapism
puberty

Bone marrow
infarction,
osteomyelitis

Skin ulcers

FIGURE 96-1. Chronic and acute complications of sickle cell disease. Sepsis is an additional potential acute complication of sickle cell disease.

demonstrated a difference in the electrophoretic pattern of sickle hemo- has been attributed to distinct haplotypes surrounding these alleles;
globin compared with normal hemoglobin and introduced the label of additional polymorphisms in several other genes appear to modify dis-
“molecular disease.” Marotta and colleagues in 1977 showed that the ease severity, including those affecting expression of the α- and β-globin
hemoglobin alteration was due to a single nucleotide change in the gene (thalassemia mutations) and γ-globin (fetal hemoglobin) genes.
encoding the β subunit of hemoglobin A. Homozygous sickle cell disease is also referred to as SS disease
or sickle cell anemia, to distinguish it from hemoglobin SC disease, a
GENETICS AND EPIDEMIOLOGY compound heterozygous combination of sickle trait and hemoglobin
C trait. Hemoglobin SC disease is clinically similar in scope to SS, but
Sickle cell disease is a general category of sickling disorders including hemoglobin SC disease on average presents milder or less frequent
the most common homozygous (HbSS) form, which is called sickle cell vaso-occlusive complications. The spectrum of SC disease overlaps
anemia. Sickle cell anemia is inherited in a classic Mendelian autosomal considerably with SS. Other compound heterozygous forms of sickle
recessive pattern, with affected individuals demonstrating complications cell disease are the S-β-thalassemias and S-α-thalassemias. A combina-
of hemolytic anemia and impaired microvascular blood flow. Usually tion of a β-globin S allele with a nonexpressing β-globin allele, called
the heterozygous carrier state, sickle trait, is completely asymptomatic, S-β -thalassemia, results in production of only hemoglobin S, and the
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although rarely vaso-occlusive events, splenic infarction, renal papillary clinical phenotype closely resembles SS. If the thalassemia allele of
necrosis, or sudden death can occur, usually under high-altitude hypoxic β-globin permits partial expression of a normal β-globin protein, the
conditions. Several other mutant β-globin alleles can induce sickling combination is called S-β -thalassemia, and like hemoglobin SC, the
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disorders when inherited in combination with the sickle trait, the most disease tends to be milder. There are several additional combinations
common of which are β-thalassemia and hemoglobin C. Although of the β-globin S allele with rare variant hemoglobins that can result in
the homozygous state typically results in severe disease, the sickle trait different severities of sickle cell disease. With S-α-thalassemias, a reduc-
appears to confer resistance to severe malaria, leading to an evolutionary tion in the amount of α-globin produced results in hemoglobin chain
selection for this carrier state in geographic regions with a high preva- imbalances that reduce the concentration of total hemoglobin in the red
lence of malaria. The sickle trait allele appears to have independently blood cell. Because hemoglobin S polymerization is reduced at lower
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arisen at least three times in Africa and once in the Arab-Indian region. intraerythrocytic hemoglobin concentrations, this reduces the severity
Migration from these regions has brought sickle cell disease to other of hemolytic anemia. In general, patients with S-thalassemias and SC
parts of the world, particularly the Caribbean, Mediterranean, and the disease have higher steady-state hemoglobin concentrations (10-12 g/dL)
North and South American regions. Some variation in disease severity than patients with homozygous Hb-SS disease (7-9 g/dL).

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