Clinical Features. From its onset, the disease runs an unremitting course punctuated by sudden crises. Homozygous sickle cell disease usually is asymptomatic until 6 months of age when the shift from HbF to HbS is complete. The anemia is moderate to severe; most patients have hematocrits of 18% to 30% (normal range, 38%–48%). The http://ebooksmedicine.net
Oxygenation Additional cycles of deoxygenation Ca2+ K+, H2O Irreversibly sickled cell Cell with dehydration and membrane damage Extensive membrane damage Deoxygenation, prolonged transit times Reversibly
Fig. 12.4 Pathophysiologyofsicklecelldisease.
chronic hemolysis is associated with hyperbilirubinemia and compensatory reticulocytosis.
Much more serious are vasoocclusive crises, which are characteristically associated with pain and often lead to tissue damage and significant morbidity and mortality. Among the most common and serious of these vasoocclusive crises are the following:
Hand-foot syndrome, resulting from infarction of bones in the hands and feet, is the most common presenting symptom in young children.
Acute chest syndrome, in which sluggish blood flow in inflamed lung (e.g., an area of pneumonia) leads to sickling within hypoxemic pulmonary beds. This exacerbates pulmonary dysfunction, creating a vicious circle of worsening pulmonary and systemic hypoxemia, sickling, and vasoocclusion. Acute chest syndrome may also be triggered by fat emboli emanating from infarcted bone.
Stroke, which sometimes occurs in the setting of the acute chest syndrome. Stroke and the acute chest syndrome are the two leading causes of ischemia-related death.
Proliferative retinopathy, a consequence of vasoocclusions in the eye that can lead to loss of visual acuity and blindness.
Another acute event, aplastic crisis, is caused by a sudden decrease in red cell production. As in hereditary spherocytosis, this usually is triggered by the infection of erythroblasts by parvovirus B19 and, although severe, is self-limited.
In addition to these crises, patients with sickle cell disease are prone to infections. Both children and adults with sickle cell disease are functionally asplenic, making them susceptible to infections caused by encapsulated bacteria, such as pneumococci. In adults the basis for “hyposplenism” is autoinfarction. In the earlier childhood phase of splenic enlargement, congestion caused by trapped sickled red cells apparently interferes with bacterial sequestration and killing; hence, even children with enlarged spleens are at risk for the development of fatal septicemia. Patients with sickle cell disease also are predisposed to Salmonella osteomyelitis, possibly in part because of poorly understood acquired defects in complement function.
In homozygous sickle cell disease, irreversibly sickled red cells are seen in routine peripheral blood smears. In sickle cell trait, sickling can be induced in vitro by exposing cells to marked hypoxia. The diagnosis is confirmed by electrophoretic demonstration of HbS. Prenatal diagnosis of sickle cell anemia can be performed by analyzing fetal DNA obtained by amniocentesis or biopsy of chorionic villi.
The clinical course of sickle cell disease is highly variable. As a result of improvements in supportive care, an increasing number of patients are surviving into adulthood. Approximately 50% of patients now survive beyond the fifth decade. Of particular importance is prophylactic treatment with penicillin to prevent pneumococcal infections, especially in children younger than age 5.