Management of acute ischemic stroke in patients with SCD is similar to that used with general patients: antiplatelet therapy, careful attention to normo-glycemia and normovolemia, and maintenance of cerebral perfusion pressure. In addition, SCD patients should receive emergent transfusion to reduce the sickle fraction to less than 30%. Patients with prior transient ischemic attack (TIA) or stroke should be on a chronic monthly transfusion regimen. Also, based on the results of the 1997 STOP I trial (Stroke Prevention Trial in Sickle Cell Anemia), children with SCD should be screened with transcranial Doppler for high velocity flow (>200 cm/second) in the internal jugular and vertebral arteries.14 Children with high velocity flow who were treated with preventative transfusion regimens had a 90% absolute risk reduction in the incidence of first stroke.
In 2001-2006, a follow-up trial (STOP 2) revealed that among patients receiving at least 30 months of chronic transfusion to prevent a first stroke 39% of those randomized to discontinue transfusion had a reversion to high risk Doppler or suffered a stroke within an average of 4.5 months. This has led many to believe that prophylactic transfusion should be a lifelong treatment.15
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Complications Seen Primarily in Adults
As the SCD population in this country has grown older, some previously uncommon complications have become more prominent. One predominantly adult complication of SCD is avascular necrosis of the femoral and humeral heads. Though clearly recognized in younger children in whom the incidence is estimated at about 3%, the major burden of femoral osteonecrosis is seen in adults older than 35, in whom prevalence reaches 50%.16 Necrosis of the humeral head can affect nearly 20% of SCD adults as well.17
It is important to recognize this complication as a new or different type of pain, separate from the vaso-occlusive pain usually experienced by SCD patients because it benefits from different therapies. Diagnosis by plain radiography is possible in the late stages, when evidence of remodeling, cystic changes, and sclerosis can be seen, but MRI has become the gold standard, with an estimated diagnostic accuracy of 90%.16 Conservative treatments include NSAIDs and steroid joint injections, but many afflicted patients may need orthopedic referral for joint replacement.
While acute chest syndrome remains a primary cause of mortality in SCD, adults with SCD are also at high risk for the chronic effects of pulmonary arterial hypertension (PAH). Thought to be uncommon in children, PAH affects up to one-third of adult SCD patients.18 Suspicion of this condition can be based on worsened fatigue, new resting hypoxemia, or increased painful crises, but experts advocate universal screening using transthoracic echocardiography. Patients with a tricuspid regurgitant jet velocity of 2.5 m/sec meet diagnostic criteria, and it is notable that the relative risk of death is 7.4 compared with SCD patients without PAH. This correlates with only moderate elevation of pulmonary pressures, suggesting that SCD patients tolerate PAH less well than other populations. Treatment options advocated include hydroxyurea, chronic transfusions, oxygen, pulmonary vasodilators such as prostacyclin and bosentan, and phosphodiesterase inhibitors such as sildenafil.
As SCD patients age, kidney disease is seen with increasing frequency, and three primary mechanisms are recognized. First, ischemic damage in the tubules causes tubular necrosis, which leads to hematuria.19 This condition can range from microscopic to severe gross hematuria, threatening urinary obstruction. Second, damage in the collecting duct impairs the body’s ability to concentrate urine, a condition that is called hyposthenuria. This condition makes SCD patients susceptible to dehydration, especially during physical exertion or in hot weather.
Interestingly, these first two mechanisms of kidney damage are also seen in patients with sickle cell trait. Finally, and most importantly, medullary interstitial fibrosis damages the glomerulus. Clinically, this is the most important mechanism because it leads to nephritic syndrome and chronic kidney disease as well as end-stage renal disease (ESRD).19