Chapter 108. Sickle Cell Disease

• Sickle cell disease causes a chronic hemolytic anemia associated with acute and chronic vaso-occlusion.
• Baseline hemodynamic and laboratory values in patients with sickle cell disease can be confused with sepsis.
• Serum creatinine levels of 1 to 1.5 mg/dL often indicate significant renal dysfunction.
• The most common intensive care management problems in patients with sickle cell disease include the acute chest syndrome, very severe anemia, sepsis, stroke, priapism, and splenic sequestration.
• Secondary pulmonary hypertension occurs in 30% of patients with sickle cell disease, often unrecognized.
• Red cell transfusion is an important treatment for most patients with sickle cell disease requiring intensive care management.
• Rapid exchange transfusion is indicated for central nervous system events, serious respiratory disease, or multiorgan failure.
• Transfusion management in patients with sickle cell disease requires investigation of alloimmunization history.
• Preoperative red cell transfusion and detailed supportive care are advisable for significant surgery in patients with sickle cell disease.

Sickle cell disease is a highly prevalent disease in the United States, affecting 1 in 500 African American infants. It is common in individuals of African, Caribbean, Mediterranean, Arab, and other Middle Eastern descent. It is a genetic disorder with an autosomal recessive inheritance pattern. Sickle cell disease is often called “the first molecular disease” because the biochemical alteration in sickle hemoglobin described by Linus Pauling in 1948 was one of the first lesions identified at the molecular level for a human disease. Sickle hemoglobin forms rod-like polymers in deoxygenated red cells in areas of the circulation, with low oxygen tension, acidosis, or hyperosmolarity. Sickle hemoglobin polymerization causes a host of secondary molecular and cellular changes, many of which impair blood flow and contribute to tissue damage. The microcirculation can be acutely or chronically impaired in virtually any organ in the body, resulting in the characteristic crisis pattern of intermittent pain and acute organ injury superimposed on the gradual development of chronic organ failure.

Despite the early progress in a molecular understanding of sickle cell disease, its treatment remained largely palliative for many decades. In recent years, the longevity of patients with sickle cell disease has been prolonged by the institution of prophylactic penicillin treatment and immunization to decrease mortality rate from pneumococcal sepsis. Chronic transfusion therapy for selected patients has improved outcome, and acute transfusion therapy is the central intervention for most complications requiring admission to the intensive care unit (ICU). Hydroxyurea, the first treatment approved by the Food and Drug Administration for sickle cell disease, decreases disease severity and mortality rate.1,2 Most recently, new paradigms have emerged regarding the pathophysiology of secondary complications of sickle cell disease, with much of this involving impairment of normal intravascular signaling via the nitric oxide (NO) pathway3–5 (Fig. 108-1). These new paradigms have triggered a wave of research seeking to translate these basic science advances into clinical practice.6 This chapter reviews general aspects of the genetics and pathophysiology of sickle cell disease, common clinical problems with ...