Atlas of pathophysiology, 2 Edition

Part II - Disorders

Hematologic Disorders

Sickle cell anemia

A congenital hemolytic anemia that occurs primarily but not exclusively in blacks, sickle cell anemia results from a defective hemoglobin (Hb) molecule (Hb S) that causes red blood cells (RBCs) to become sickle-shaped. Such cells clog capillaries and impair circulation, resulting in chronic ill health (fatigue, dyspnea on exertion, swollen joints), periodic crises, long-term complications, and early death.

If both parents are carriers of sickle cell trait (or another hemoglobinopathy), each child has a 25% chance of developing sickle cell anemia. Approximately one out of every 500 blacks has sickle cell anemia. The defective Hb S–producing gene may have persisted because, in areas where malaria is endemic, the heterozygous sickle cell trait provides resistance to malaria and is actually beneficial.

Age Alert

Half of patients with sickle cell anemia once died by their early twenties; few lived to middle age. Earlier diagnosis and more effective treatment have improved the prognosis of sickle cell anemia. Most patients now survive well into adulthood.

Causes

·   Homozygous inheritance of the gene that produces Hb S

·   Heterozygous inheritance of this gene results in sickle cell trait, which is usually asymptomatic

Pathophysiology

Hb S becomes insoluble whenever hypoxia occurs. As a result, these RBCs become rigid and elongated, forming a crescent or sickle shape. Such sickling can produce hemolysis (cell destruction). In addition, these altered cells make blood more viscous and tend to accumulate in smaller blood vessels and capillaries. The result is loss of normal circulation, swelling, tissue infarctions, and pain. Furthermore, the blockage causes anoxic changes that lead to further sickling and obstruction. Each patient with sickle cell anemia has a different hypoxic threshold and particular factors that trigger a sickle cell crisis. Illness, exposure to cold, stress, acidotic states, or a pathophysiologic process that pulls water out of the sickle cells precipitates a crisis in most patients. The blockages then cause anoxic changes that lead to further sickling and obstruction.

Signs and symptoms

·   Tachycardia, cardiomegaly, systolic and diastolic murmurs

·   Pulmonary infarctions, which may result in cor pulmonale

·   Stroke

·   Chronic fatigue, unexplained dyspnea or dyspnea on exertion

·   Ischemic leg ulcers (especially around the ankles)

·   Increased susceptibility to infection

Occlusive or infarctive crises

·   Severe abdominal, thoracic, muscular, or bone pain

·   Worsening jaundice, dark urine

Aplastic crisis

·   Pallor

·   Lethargy, sleepiness, coma

·   Dyspnea

·   Markedly decreased bone marrow activity, RBC hemolysis

Diagnostic test results

·   Electrophoresis shows Hb S.

·   Stained blood smear shows the presence of sickled cells.

·   Laboratory studies show low RBC count, elevated white blood cell and platelet counts, decreased erythrocyte sedimentation rate, increased serum iron levels, decreased RBC survival, and reticulocytosis.

·   Lateral chest X-ray shows “Lincoln log” deformity in the vertebrae of many adults and some adolescents.

Treatment

·   Prophylactic penicillin before age 4 months

·   Oral hydroxyurea to reduce the number of painful crises

·   Packed RBC transfusions

·   Sedation

·   Analgesics

·   Oxygen

·   Oral or I.V. fluids

·   Iron and folic acid supplements

·   Antibiotics

P.257

PERIPHERAL BLOOD SMEAR IN SICKLE CELL ANEMIA

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SICKLE CELL CRISIS

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