Patients with sickle cell disease (SCD) are at high risk for a broad range of acute and chronic conditions affecting many of the body’s systems and carrying a high association with morbidity.

Given the broad range of potential manifestations of the disease, coordinating care among primary care providers, specialists, emergency departments, laboratories and hospitals can dramatically improve outcomes.

“Treating the sickle cell disease can improve outcomes for the many potential complications of SCD, but getting ahead of the complications by identifying those at risk and with early signs can lead to much better outcomes,” said Ashok B. Raj, M.D., a pediatric hematologist/oncologist and medical director of Norton Children’s Cancer Institute, affiliated with the UofL School of Medicine.

Dr. Raj is also director of the pediatric erythrocytapheresis program at Norton Children’s Cancer Institute.

Preventive interventions and screening opportunities

The following is modified from the National Institutes of Health’s Evidence-Based Management of Sickle Cell Disease; Expert Panel Report, 2014

Invasive pneumococcal infection

Young children with sickle cell anemia (SCA) have a very high risk for septicemia and meningitis due to defective spleen function.

Top recommendations

• Administer oral penicillin prophylaxis (125 milligrams for ages less than 3 years and 250 milligrams for ages 3 years or greater) twice daily until age 5 in all children with the HbSS (one sickle cell gene “S” from each parent) form of SCD.
• Assure that people of all ages with SCD follow a special vaccination schedule for pneumococcal and meningococcal vaccines
• Remind people with SCD, their families and caregivers to seek immediate medical attention whenever fever (temperature greater than 101.3 F or 38.5 C) occurs, due to the risk for severe bacterial infections.

Screening for renal disease

Sickle cell nephropathy is a major complication of SCD, causing tubular and medullary dysfunction. Glomerular enlargement, perihilar focal segmental glomerulosclerosis and global sclerosis are the most common.

Top recommendation

• Screen all individuals with SCD, beginning by age 10, for micro-
• If the result is negative, repeat screening annually. If the result is positive, perform a first morning void urine micro albumin-creatinine ratio. If abnormal, consult with or refer to a renal specialist.

Screening for hypertension

Individuals with the HbSS form of SCD often have significantly lower diastolic, systolic and mean blood pressure.

Top recommendations

• In children with SCD, measure blood pressure, and evaluate and treat hypertension following recommendations from the National Heart, Lung, and Blood Institute’s “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.”

Screening for retinopathy

All SCD patients, and especially those with HbSC (one sickle cell gene “S” from one parent and one abnormal hemoglobin gene “C” from the other), are at risk for retinal disease. One study found proliferative retinopathy in 4.3% of children with SCD. Another study in Jamaica found visual acuity loss attributed to retinopathy was in 10% of untreated eyes.

Top recommendations

• Refer SCD patients to an ophthalmologist for a dilated eye examination beginning at age 10.
• Rescreen those with a normal dilated retinal examination every one or two years.
• Refer patients with suspected retinopathy to a retinal specialist.

Screening for risk of stroke using neuroimaging

Stroke is one of the most common and devastating complications of SCD. Without efforts to prevent stroke, about 10% of children with SCA will have overt stroke. Overt stroke recurs in most children with SCA who do not receive chronic transfusions or successful hematopoietic stem cell transplantation.

Adults with SCA have a high risk of both ischemic and hemorrhagic stroke.

Top recommendations

• In children with SCA, screen annually with transcranial Doppler (TCD) imaging according to methods employed in STOP study 1 and STOP study 2, beginning at age 2 and continuing until at least age 16.
• In children with conditional (170–199 cm/sec) or elevated (>200 cm/sec) TCD results, refer to a specialist with expertise in chronic transfusion therapy aimed at preventing stroke.
• In children with genotypes other than SCA (e.g., HbS β+-thalassemia or HbSC), do not perform screening with TCD.

Screening for pulmonary disease

Of children with SCD, 20% to 48% have respiratory conditions A study of individuals with SCA and asthma had a more than twofold higher risk of mortality than patients with just SCA.

Top recommendations

Assess children and adults with SCD for signs and symptoms of respiratory conditions such as asthma, chronic obstructive pulmonary disorder (COPD), restrictive lung disease or obstructive sleep apnea.

Perform further assessment, including pulmonary function tests to determine the cause and treatment plan in children and adults with SCD found to have signs or symptoms of respiratory conditions.

Reproductive counseling

There is an increased risk of adverse pregnancy outcomes in SCD patients as well as risk of maternal morbidity and mortality.

Top recommendations

For patients with SCD:

• Encourage each person and couple affected by SCD to have a reproductive life plan.
• As a part of primary care visits, provide risk assessment and educational and health promotion counseling (or refer to individuals with expertise in these disciplines) to all patients of childbearing age to reduce reproductive risk and improve pregnancy outcomes.
• Provide contraceptive counseling, if desired, to prevent unintended pregnancy, and if pregnancy is desired, provide preconception counseling.
• If the partner of a patient with SCD has unknown SCD or thalassemia status, refer the partner for hemoglobinopathy screening.
• After testing, refer couples who are at risk for having a potentially affected fetus and neonate for genetic counseling.

Contraception

Hormonal contraceptives may decrease menstrual blood flow, leading to higher hemoglobin levels. Progestin-only hormonal contraceptives lower the risk of thromboembolism compared with use of estrogen-containing contraceptives and have been shown to be safe for patients with SCD.

Intrauterine devices (IUDs) and intrauterine implants carry modest risks associated with the insertion procedure, while sterilization carries risks associated with the surgical procedure. There is no evidence that IUDs pose an increased risk for patients with SCD.

Top recommendations

• Progestin-only contraceptives (pills, injections, and implants), levonorgestrel IUDs, and barrier methods have no restrictions or concerns for use in patients with SCD.
• If the benefits are considered to outweigh the risks, combined hormonal contraceptives (pills, patches and rings) may be used in patients with SCD.

Clinical preventive services

An overemphasis on treating SCD may lead to some patients failing to get recommended clinical preventive services.

Top recommendations

Newborn screening

• SCD screening with clinical consideration of confirmatory test within two months
• Antibiotic prophylaxis for pneumococcal infections

Supplemental immunization schedule for children with SCD, per Centers for Disease Control and Prevention:

• Menveo
  • Dose 1 at age 8 weeks: four-dose series at 2, 4, 6, 12 months
  • Dose 1 at age 3 to 6 months: three- or four- dose series (dose 2 [and dose 3 if applicable] at least eight weeks after previous dose until a dose is received at age 7 months or older, followed by an additional dose at least 12 weeks later and after age 12 months)
  • Dose 1 at age 7 to 23 months: two-dose series (dose 2 at least 12 weeks after dose 1 and after age 12 months)
  • Dose 1 at age 24 months or older: two-dose series at least eight weeks apart
• Menactra
  • Age 9 to 23 months: Not recommended
  • Age 24 months or older: two-dose series at least eight weeks apart
  • Menactra must be administered at least four weeks after completion of PCV13 series.
• MenQuadfi
  • Dose 1 at age 24 months or older: two-dose series at least 8 weeks apart