Porth's Essentials of Pathophysiology, 4e

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Disorders of Red Blood Cells

C h a p t e r 1 3

Diagnosis andTreatment. The signs and symptoms of sickle cell disease make their appearance during infancy. Neonatal diagnosis of sickle cell disease is made on the basis of clinical findings and hemoglobin solubility results, which are confirmed by hemoglobin electropho- resis. Prenatal diagnosis is done by the analysis of fetal DNA obtained by amniocentesis. 7 In the United States, screening programs have been implemented to detect newborns with sickle cell dis- ease and other hemoglobinopathies. Cord blood or heel-stick samples are subjected to electrophoresis to separate the HbF from the small amount of HbA and HbS. Other hemoglobins may also be detected and quantified by further laboratory evaluation. According to the National Newborn Screening and Genetics Resource Center (NNSGRC), all 50 states require screening of all newborns regardless of ethnic origin. The clinical course of persons with sickle cell dis- ease is highly variable. As a result of improvements in supportive care, an increasing number of persons are surviving into adulthood and producing offspring. Of particular importance is the early prophylactic treat- ment with penicillin to prevent pneumococcal infec- tion. Treatment should begin as early as 2 months of age and continued until at least 5 years of age. 11 Maintaining full immunization, including the H. influenzae and hepatitis B vaccines, is recommended. The National Institutes of Health Committee on Management of Sickle Cell Disease also recommends administration of the 7-valent pneumococcal vaccine beginning at 2 to 6 months of age 11 (see Chapter 25). The 7-valent vaccine should be followed by immuni- zation with the 23-valent pneumococcal vaccine at 24 months of age or later. Most recent recommenda- tions (Advisory Committee on Immunization Practices 2013) have also included the use of the 13-valent pneu- mococcal conjugate vaccine in children ages 6 to 18 years old with immunocompromising conditions such as functional asplenia. Hydroxyurea, an inhibitor of DNA synthesis, has been shown to reduce pain crises and prevent the complications of sickle cell disease. The drug pro- duces an increase of HbF in red cells by decreasing the terminal differentiation of erythroid stem cells into HbS; acts as an anti-inflammatory agent by inhibiting the production of white blood cells; and is oxidized by heme groups to produce nitric oxide, a potent vasodilator and inhibitor of platelet aggregation. 5 Although the drug halves pain episodes and pulmo- nary complications, approximately 40% of persons do not respond. 12 Other therapies under investigation include drugs that affect globin gene expression; pre- vent hemoglobin polymerization, membrane damage, and cell dehydration; or inhibit sickle cell adhesion to endothelial cells. 12 Bone marrow or stem cell trans- plantation has the potential for cure in symptomatic children but carries the risk of graft-versus-host dis- ease. Progress in gene therapy to treat sickle cell dis- ease has been slow but promising, and may be a future option.

Retinal infarcts: Blindness Stroke

Lung infarcts: Pneumonia Acute chest syndrome

Iron overload: Heart Liver

Atrophic spleen

Pigment gallstones

Kidney infarcts: Chronic kidney disease

Avascular necrosis of femoral head

Painful infarcts:

Osteomyelitis

Bones of fingers and toes

Skin ulcers

FIGURE 13-10. Clinical manifestations of sickle cell disease.

In addition to these crises, persons with sickle cell disease are prone to infections. Because of the spleen’s sluggish blood flow and low oxygen tension, hemoglo- bin in red cells traversing the spleen becomes deoxy- genated, causing ischemia. Splenic injury begins in early childhood, is characterized by intense congestion, and is usually asymptomatic. The congestion causes functional asplenia and predisposes the person to life- threatening infections by encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influen- zae type b, and Klebsiella species. Neonates and small children have not had time to create antibodies to these organisms and rely on the spleen for their removal. In the absence of specific antibody to the polysaccharide capsular antigens of these organisms, splenic activity is essential for removing these organisms when they enter the blood.