Figure 1. Passage of the sickle cell gene from parents to offspring
The abnormal hemoglobin S found in such patients' RBCs becomes insoluble whenever hypoxia occurs. As a result, these RBCs become rigid, rough, and elongated, forming a crescent or sickle shape. Such sickling can produce hemolysis (cell destruction). In addition, these altered cells tend to pile up in capillaries and smaller blood vessels, making the blood more viscous. Normal circulation is impaired, causing pain, tissue infarctions, and swelling. Such blockage causes anoxic changes that lead to further sickling and obstruction.
Figure 2. Normal and sickled red blood cells
Symptoms. Characteristically, sickle cell anemia produces tachycardia, cardiomegaly, systolic and diastolic murmurs, pulmonary infarctions (which may result in cor pulmonale), chronic fatigue, unexplained dyspnea or dyspnea on exertion, hepatomegaly, jaundice, pallor, joint swelling, aching bones, chest pains, ischemic leg ulcers (especially around the ankles), and increased susceptibility to infection. Such symptoms usually don't develop until after 6 months of age, since large amounts of fetal hemoglobin protect infants for the first few months after birth. Low socioeconomic status and related problems, such as poor nutrition and low educational levels, may delay diagnosis and supportive treatment.
Periodic crises. Infection, stress, dehydration, and conditions that provoke hypoxia--strenuous exercise, high altitude, unpressurized aircraft, cold, and vasoconstrictive drugs--may all provoke periodic crisis. Painful crisis. A painful crisis (vaso-occlusive crisis, infarctive crisis), the most common crisis and the hallmark of this disease, usually doesn't appear until age 5 but recurs periodically thereafter. It results from blood vessel obstruction by rigid, tangled sickle cells, which causes tissue anoxia and possibly necrosis. It is characterized by severe abdominal, thoracic, muscular, or bone pain and possibly increased jaundice, dark urine, or a low-grade fever. Autosplenectomy, in which splenic damage and scarring is so extensive that the spleen shrinks and becomes impalpable, occurs in patients with long-term disease. Such autosplenectomy can lead to increased susceptibility to Diplococcus pneumoniae sepsis, which can be fatal without prompt treatment. After the symptoms of crisis subside (in 4 days or several weeks), infection may develop, often indicated by lethargy, sleepiness, fever, or apathy.
Anaplastic crisis. Associated with infection is the anaplastic crisis (megaloblastic crisis) which results from bone marrow depression and is associated with infection, usually viral. It is characterized by pallor, lethargy, sleepiness, dyspnea, possible coma, markedly decreased bone marrow activity, and RBC hemolysis.
Acute sequestration crisis. In infants between 8 months and 2 years old, an acute sequestration crisis may cause sudden massive entrapment of red cells in the spleen and liver. This rare crisis causes lethargy and pallor, and if untreated, can progress hypovolemic shock and death. In fact, it's the most common cause of death in sickle cell children under 1 year.
Hemolytic crisis. Hemolytic crises are quite rare and usually occur in patients who have glucose-6-phosphate dehydrogenase (G-6-PD) deficiency with sickle cell anemia. It probably results from complications of sickle cell anemia, such as infection, rather than from the disorder itself. Hemolytic crisis causes liver congestion and hepatomegaly as a result of degenerative changes. It worsens chronic jaundice although increased jaundice doesn't always point to a hemolytic crisis.
Any of these crises are possible in sickle cell anemia patients with pale lips, tongue, palms, or nail beds; lethargy; listlessness; sleepiness, with difficulty awakening; irritability; severe pain; temperature over 104# F (40# C) or a fever of 100# F (38# C) that persists for 2 days.
Long-Term Complications. Sickle cell anemia also causes a number of long-term complications. Typically, children with sickle cell anemia are small for the age, and puberty is delayed. (However, fertility is not impaired.) If they reach adulthood, their bodies tend to be spiderlike--narrow shoulders and hips, long extremities, curved spine, barrel chest, and elongated skull. An adult usually has complications stemming from infarction of various organs, such as retinopathy and nephropathy. Premature death usually results from infection, or repeated occlusion of small blood vessels and consequent infarction or necrosis of major organs. For example, cerebral blood vessel occlusion causes cerebrovascular accident.
