Table 1.

Commonly recognized sickle-related complications in adults

ComplicationDefinitionMajor risk factors and prevalence
PainAcute pain, most commonly in the long bones, chest, backEpisodes of acute pain commence from around 6 mo of age and continues throughout life
Adults with SCD experience pain on >54% of days but only access health care on 3.5% of days.36
Chronic pain is pain lasting for >3 moEstimated to occur in >50% adults with SCD; 40% of adults with SCD take daily opioids.99
AnemiaAcute anemia: a decline in hemoglobin of 2 g/dL or more from steady-state valuesVariety of causes including infection (transient red cell aplasia most commonly caused by acute parvo virus B19); acute hemolysis accompanying severe VOC, delayed transfusion reaction
Chronic hemolytic anemia: severity increases with age and major contributor to insidious organ dysfunctionChronic hemolysis predisposes to gallstones and gallbladder disease
ACSAcute onset of respiratory symptoms with features similar to pneumonia24.5/100 PYO in young children; 8.8/100 PYO in older adults101; outcome more severe in adults
Pulmonary hypertensionMean pulmonary artery pressure of >25 mm Hg at rest, measured by right heart catheterization6.0%-10.4% prevalence during adulthood.41-43,46,47
Cardiac dysfunctionLeft ventricular failure is most common abnormalityUniversal to some degree in adults over age 30.44 Diffuse myocardial fibrosis is a common pathology, and associated with diastolic dysfunction, anemia, and high NT-proBNP. Fibrosis-mediated diasystolic dysfunction may contribute to elevated TRV in older adults via pulmonary venous hypertension.45
Chronic sickle lung diseaseProgressive restrictive lung function deficit with fibrotic changes on high resolution CT scanRestrictive lung defects seen in >70% adults.38
AsthmaAsthma is seen more commonly in children than in adults
Sleep-disordered breathingSleep disordered breathing is seen in 40%-60% of adults.19
StrokeAcute cerebrovascular accidentEffective screening and prevention have dramatically reduced infarctive stroke in children. Hemorrhagic stroke affects both children and adults, threefold more in adults.102 Risk factors for ischemic stroke include hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and renal disease in adults.103
Silent cerebral infarctsClinically silent lesions of 3 mm or more on magnetic resonance imaging scanningImportant contributing factor to neurocognitive deficits; 53% in adults.20
Acute renal injuryAcute deterioration in renal function2% during pain crisis and up to 14% during ACS
Renal failureDeteriorating renal function, reduced concentrating ability, proteinuria, and progressive renal failureAdvanced disease (stage III-IV) in 4%-18% of adults.21
PriapismUnwanted painful and sustained erection of the penis for >4 h, often recurrent or persistent20%-89% lifetime prevalence in boys and men.104
Avascular necrosis of bonesAvascular necrosis of any bone, most commonly the femoral head and shoulder joint>20% lifetime prevalence of symptomatic disease. Increased prevalence of asymptomatic disease.105
Leg ulcerationMost commonly around the malleolar regions>14% lifetime prevalence.106,107
CholelithiasisGallstones and gallbladder diseaseImportant genetic modifier is polymorphic (AT) repeats in promoter of UGT1A1 gene.100 Gallbladder disease in 28% at median age of 28 y.11
RetinopathyGrade 2-4 retinopathy>30% of patients.108 Increased in HbSC.109
  • ACS, acute chest syndrome; AT, adenine-thymidine; proBNP, N-terminal pro b-type natriuretic peptide; PYO, person-years of observation, VOC, vaso-occlusive crisis.