Description
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic hemolysis, acute painful vaso-occlusive crises, and end-organ damage
Epidemiology
Incidence
- Most common in people of African and Mediterranean descent; also common in people from the Caribbean, South and Central America, Middle East, and parts of India
- Greater than 230,000 affected children are born every year in sub-Saharan Africa.
- In North America and Europe, ~2,600 and 1,300 affected children are born every year, respectively (1).
Prevalence
- Prevalence of SCD is highest in sub-Saharan Africa.
- Affects 50,000–100,000 people in the US.
- 1 in every 600 African-Americans has SCD.
Morbidity
- Approximately 30% of patients have severe disease with widespread organ damage and early death, 60% have a less devastating clinical course, and 10% remain relatively well most of their life.
- Risk factors for increased perioperative morbidity include increased age, pregnancy, and preexisting infections.
Etiology/Risk Factors
- Hemoglobin A (HbA) is the predominant hemoglobin in adulthood; it has 2
and 2
globin chains. A single point mutation in the 6th codon on the globin chain results in substitution of valine for glutamic acid and hemoglobin S (Sickle Hb – molecular hallmark of SCD). This defect creates a new hydrophobic spot on the outer portion of the molecule (normally hydrophilic and in contact with plasma) (2). - In both normal and sickle Hb, deoxygenated Hb results in a small hydrophobic patch; thus in SCD, there is a double hydrophobic spot that seeks out and sticks to other hydrophobic spots on other Hb molecules. As a result, deoxygenated Hb aggregates into chains; the tetramers stick to each other and polymerize (form long fibers) instead of remaining independent.
- Risk factors that favor "sickling"
- Hb deoxygenation secondary to hypoventilation and hypoxemia
- Decreased perfusion secondary to decreased cardiac output, hypotension, hypovolemia/dehydration, and cardiopulmonary bypass
- Venous stasis secondary to patient immobility, extremity tourniquets, and improper patient positioning
- Metabolic factors such as acidosis, hypothermia, and infection
- Alcohol binges, high altitudes, and prolonged airline flights also precipitate complications in SCD patients.
Physiology/Pathophysiology
- "Sickling" results in the normally pliable biconcave erythrocyte assuming a rigid sickle shape on deoxygenation. This causes cell membrane damage, hemolysis, clogging of the microcirculation, and ischemic organ damage with vaso-occlusive crises.
- Vaso-occlusive processes account for the majority of complications; clinical presentation depends on the vascular bed affected
- Increased hemolysis
- Decreases the red blood cell lifespan from ~120 days to ~15 days, resulting in anemia.
- Disrupts intracellular nitric oxide (NO) metabolism and hence decreases NO bioavailability. This causes increased endothelial oxidant and shear stress with resultant endothelial inflammation and exacerbation of vasoconstriction and tissue ischemia (3).
- Oxyhemoglobin curve is shifted to the right (P50 = 31 mm Hg, compared to normal P50 = 27 mm Hg). This reflects the decreased affinity of Hb for oxygen.
Pregnancy Considerations
| Painful crises occur more commonly during pregnancy |
- Pathophysiological changes that accompany SCD may necessitate a surgical procedure such as splenectomy, cholecystectomy, skin grafting for leg ulcers, curettage of osteomyelitic bone cavities, acute abdomen, orthopedic prosthetic surgery, Cesarean section, etc.
- Since reversal of the sickling process is difficult, the focus is on prevention. Thus, goals for perioperative care include avoidance of acidosis, hypoxemia, dehydration, venous stasis, and hypothermia.
- Patients may have increased narcotic requirements from chronic use.