Management of Sickle Cell Disease in Children

Abstract

Sickle cell disease (SCD) is a heterogeneous inherited disorder of hemoglobin that causes chronic hemolytic anemia, vaso-occlusion, and endothelial dysfunction. These physiologic derangements often lead to multiorgan damage in infancy and throughout childhood. The most common types of SCD are homozygous hemoglobin S (HbSS disease), hemoglobin SC disease, and sickle β thalassemia. HbSS disease and sickle β⁰ thalassemia often are referred to as sickle cell anemia because they have similar severity. Screening and preventive measures, including infection prophylaxis and vaccination, have significantly improved outcomes for children with SCD. Evidence-based therapies, such as hydroxyurea and transfusion, play an important role in preventing progression of select complications. Many chronic complications develop insidiously and require multidisciplinary care for effective treatment. Primary care physicians, as well as physicians in many other disciplines, may care for these patients and should be familiar with the potential acute and chronic complications of this disease. This review addresses healthcare maintenance guidelines, common complications, and recommendations for management of pediatric patients with SCD.

Sickle cell disease (SCD) is an inherited abnormality of hemoglobin leading to sickling of red blood cells, anemia, and complications from vaso-occlusion. It is identified in 1 in 300 to 400 African American births and in approximately 2000 infants each year in the United States by universal newborn screening for sickle hemoglobinopathies. From 1991 to 2011, the highest calculated incidence of SCD from newborn screening data was observed in Washington, DC (1:437), followed by Mississippi (1:683) and South Carolina (1:771).¹ The majority of infants (60%–65%) are diagnosed as having homozygous SS disease (HbSS) or are compound heterozygotes, co-inheriting hemoglobins S and C (HbSC, 25%-30%) or hemoglobin S and a β thalassemia mutation (HbSβ^0/+ thalassemia, 9%). People with HbSS and HbSβ⁰ thalassemia, on average, have more severe disease in contrast to those with HbSC and HbSβ⁺ thalassemia.² Co-inheritance of α-globin mutations or high fetal hemoglobin expression often leads to decreased disease severity even in patients with HbSS.³ Median survival is 40 to 45 years for people with HbSS, 65 years for people with HbSC, and 73 years for people with HbSβ⁺.

SCD causes chronic hemolysis and vascular endothelial injury, with an increased risk of acute chronic damage to organ systems. Routine screening and education in childhood are essential to identify complications in the early stages, permitting interventions to minimize long-term morbidity in vulnerable patients.

Most infants identified as having SCD on newborn screening are referred to their local hemoglobinopathy center for ongoing surveillance. The first visit to the pediatric hematologist can be difficult for families, particularly when no previous family members have had SCD. The high level of fetal hemoglobin of infancy is generally protective, yet infants with SCD may experience a number of complications. A discussion of the full spectrum of complications usually is reserved for later visits, after the family has processed and assimilated the diagnosis. The first visit includes education about common complications in infancy, such as fever, dactylitis, and splenic sequestration.

Acute and Chronic Complications by Organ System

Cardiopulmonary Disease

Acute chest syndrome (ACS) is the second most common reason for hospitalization and the leading cause of death in patients with SCD.^A Defined as a new infiltrate on chest radiography and one or more signs or symptoms of lower respiratory tract disease (eg fever, cough, chest pain, hypoxemia, dyspnea, tachypnea), ACS is caused by in situ sickling, infection, or emboli from infarcted bone marrow. Children with asthma or lower airway obstruction have a higher risk of developing ACS.^4,5 ACS can be mild to severe, including progression to respiratory and multiorgan system failure. Initial management of ACS includes oxygen support, appropriate pain control, a parenteral cephalosporin and oral macrolide, and incentive spirometry. If the patient's clinical status declines, then simple transfusion to a hemoglobin of 10 g/dL or red cell exchange transfusion for severe ACS is warranted to improve oxygen-carrying capacity and alleviate ventilation-perfusion mismatch.

Respiratory symptoms (wheezing), lower airway obstruction, and the diagnosis of asthma (20%–48%) are common in children with SCD and are associated with more frequent pain, ACS, and increased mortality.^5–7 Other pulmonary function abnormalities include restrictive lung disease, which becomes more common with increasing age, and mixed obstruction/restriction. Sleep-disordered breathing was frequent in the Sleep and Asthma Cohort study: 41% of children with SCD had mild obstructive sleep apnea (OSA; apnea-hypopnea index ≥1) and 10% had moderate to severe OSA (apnea-hypopnea index ≥5).⁸ Hypoxemia, hypercapnia, and acidosis may occur as a result of OSA and may increase sickling of red blood cells. Despite the established risks associated with asthma and pulmonary function abnormalities in SCD, data related to early intervention/treatment and the role of screening and prevention are lacking. The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines do not recommend routine screening of asymptomatic patients with SCD with pulmonary function tests or sleep studies.^B The guidelines do recommend screening for signs and symptoms during clinical encounters. Children with asthma symptoms or wheezing should be treated according to asthma guidelines, with a low threshold for referral to an asthma specialist. Pulmonary function tests should be considered in children with recurrent ACS episodes or with severe or uncontrolled asthma.⁹ Children with SCD who snore should undergo a diagnostic nocturnal polysomnogram.

Pulmonary hypertension (elevated resting mean arterial pressure of ≥25 mm Hg) occurs in SCD because of chronic vascular changes that result from arginine depletion, impaired nitric oxide bioavailability, and the release of free hemoglobin from red blood cells. It also can develop secondary to chronic pulmonary or thromboembolic disease in SCD. Both pulmonary arterial and venous hypertension occur in SCD. Screening echocardiography showing elevated tricuspid regurgitant velocity (≥250 cm/second) is associated with increased morbidity and mortality in adults with SCD.^C This correlates poorly with pulmonary artery pressures by catheterization, and there is no increased mortality in children with SCD and increased tricuspid regurgitant velocity. The 2014 NHLBI guidelines do not recommend for or against routine screening of asymptomatic children or adults with SCD with echocardiograms because the evidence is insufficient^10,11; however, an echocardiogram should be considered to evaluate unexplained hypoxemia, exercise intolerance, and advanced lung disease, including restrictive lung disease.

Gastrointestinal System

Chronic hemolysis can cause cholelithiasis with pigment stones in 10% to 50% in children with SCD.^12–15 Children may be initially asymptomatic or may present with right upper quadrant pain and jaundice, which are associated with direct hyperbilirubinemia. Cholecystectomy is recommended in patients with symptoms to prevent complications such as choledocholithiasis, cholecystitis, ascending cholangitis, or pancreatitis.

Children, particularly with sickle cell anemia (SCA), can develop sickle hepatopathy or intrahepatic cholestasis, with direct hyperbilirubinemia, as high as 13 to 76 mg/dL, without evidence of infection or bile duct obstruction. Some patients have mild disease without hepatic dysfunction, whereas others develop fulminant liver failure. Emergent exchange transfusion appears to be the only effective therapy for severe cases.^16,17

Genitourinary System

Boys with SCD and their parents should be educated about priapism, which can affect males of all ages with any sickle genotype. Priapism may occur in a stuttering (multiple episodes lasting <2–3 hours) or prolonged manner. Home interventions include exercise, warm baths, ejaculation, urination, analgesics, and increased hydration. Patients are instructed to seek medical attention if priapism lasts for >4 hours to prevent fibrosis and impotence. In the emergency department setting, intravenous fluids, pain control, and aspiration and irrigation of the corpus cavernosum and intrapenile injection of α-adrenergic agents often are used. Erectile dysfunction ultimately develops in approximately 40% of men who experience recurrent episodes of priapism.¹⁸ We recommend against transfusion for the immediate therapy of priapism.¹¹

Immune System/Spleen

The onset of splenic dysfunction occurs as early as 5 months of age¹⁹ and results in greatly increased infections with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae type B. Before routine prophylaxis with penicillin, the incidence of bacteremia ranged from 3.7 to 8.3 cases per 100 person-years, and pneumococcal and Haemophilus infections were associated with 14.5% and 20% mortality rates.² In a randomized, double-blinded, placebo-controlled trial, Gaston et al reported an 84% reduction in pneumococcal sepsis in the penicillin group.²⁰ Penicillin 125 mg twice daily is strongly recommended for all infants with SCA, increasing to 250 mg twice daily at age 3, and continuing until the child is at least 5 years old. Morbidity and mortality from infection have declined substantially as a result of antibiotic prophylaxis and inclusion of conjugated pneumococcal and Haemophilus influenzae type B vaccines in infancy. The benefit for children with HbSC and HbSβ⁺ is unclear, but many pediatric hematologists still recommend prophylactic measures.

Although pneumococcal sepsis is a rare event, infection in fully immunized patients still occurs.^21,22 Fever also may signify other infections such as parvovirus, pyelonephritis, cholecystitis, osteomyelitis, or ACS. Providers should reinforce the importance of preventing infections by penicillin prophylaxis and immunizations and being evaluated immediately for fevers of 101.3°F (38.5°C) or higher. A complete blood count (CBC) with differential and reticulocyte counts should be compared with baseline values. Peripheral blood cultures should be obtained before the administration of parenteral antibiotics, usually a third-generation cephalosporin. Additional studies such as chest radiography or urine culture may be indicated, depending on clinical features.

Aplastic crisis may accompany a febrile illness. Parvovirus B19 is the most common cause of aplastic crisis in patients with SCD, although other viral infections can cause myelosuppression. Parvovirus infects erythrocyte precursors, suppresses erythropoiesis, and causes severe anemia in people with high red cell turnover. Children with aplastic crisis may present with syncope or hypotension or with gradual worsening of fatigue and pallor. The anemia often is severe and the reticulocyte count is typically <1%. Patients with symptomatic or severe anemia caused by aplastic crisis should receive slow, small-aliquot transfusions to avoid congestive heart failure. Patients with high baseline reticulocyte counts who do not require immediate transfusion should be studied closely with a daily CBC and reticulocyte count until no longer reticulocytopenic to ensure transfusion, if needed.

Splenic sequestration is another common cause of acute exacerbation of anemia. Most children with HbSS autoinfarct their spleen by age 4 years, whereas patients with HbSC and HbSβ thalassemia typically retain significant splenic tissue longer.^D Before autoinfarction, children may experience rapid enlargement of the spleen caused by sequestration of sickled cells. The spleen examination is taught to the family during their initial visits because they are often the first to detect splenomegaly. Children with severe sequestration are at risk for shock and usually have a decrease in hemoglobin of ≥2 g/dL from baseline, reticulocytosis, and thrombocytopenia. Support of intravascular volume and restoration of oxygen-carrying capacity are warranted; small transfusions of packed red blood cells (5 mL/kg) should be considered because often the spleen subsequently releases sequestered erythrocytes. Recurrence is common; therefore, splenectomy is recommended in patients with recurrent acute splenic sequestration or symptomatic hypersplenism.

Neurologic System

Acute painful vaso-occlusive crisis (VOC) is the most common symptom and reason for hospitalization among children with SCD. Although vaso-occlusion is the hallmark event leading to pain, complex interactions between cellular and molecular mediators may initiate and propagate the event. Further elucidation of these factors may lead to the development of innovative targeted therapies.^23,24 VOC in young children often affects the hands and feet, causing swelling and tenderness, which is called dactylitis. Mild to moderate pain can be managed at home with heat, distraction, ibuprofen, and oral opiates. Severe pain should be treated within 30 minutes of triage or 60 minutes of registration for emergency care with maintenance fluids if the child is unable to drink, anti-inflammatory agents, and opiates. Severe pain necessitates treatment with parenteral opiates, which can be administered on a scheduled basis or by patient-controlled analgesia. Investigation of causes of pain other than SCD can occur simultaneous with pain management. An individualized protocol, developed by the patient and his or her SCD medical team, can be helpful to expedite the patient's care in the acute setting. Patients can be discharged from the hospital once their pain can be managed with oral analgesics. We recommend encouraging ambulation and incentive spirometry to reduce the risk of ACS. Oxygen should be reserved for patients with arterial oxygen saturation <95% and transfusion avoided in those with acute pain and no other indication for transfusion.¹¹

Chronic pain is a challenging complication in adolescents and adults with SCD, affecting quality of life and productivity. Pain is defined as chronic if it lasts more than 3 months. It can result from chronic injury to joints, as in avascular necrosis, which leads to characteristic radiographic changes in later stages; patients may benefit from physical therapy or surgical interventions if the pain is severe. Chronic inflammation and reperfusion injury to tissues and nerves can lead to peripheral nerve damage and central sensitization, manifesting as allodynia and hyperalgesia.²³ Chronic pain can be deep and achy in nature or can be neuropathic, with patients complaining of burning, numbness, or tingling. Symptoms of pain may be compounded by concurrent mood disorder, social isolation, poor self-esteem, shame, and other factors. Treatment is difficult and may involve a combination of nonsteroidal anti-inflammatory agents; judicious opioid use; anticonvulsants; antidepressants; and multidisciplinary approaches, including massage, acupuncture, physical therapy, or cognitive-behavioral therapy.

The Centers for Disease Control and Prevention has issued guidelines on the use of chronic opioids, given the alarming nationwide increase in opioid-related morbidity and deaths; however, these guidelines do not apply to children, nor do they specifically address the nuances of pain management associated with SCD.²⁵ There is a paucity of data on appropriate opioid practices, development of tolerance or addiction, and nonopioid pharmacologic options for SCD-associated acute and chronic pain. We recommend using functional outcomes to evaluate the effectiveness of opiates and other strategies to treat pain in people with SCD. It is important to minimize the potential harms of opiates by obtaining appropriate informed consent (opiate agreement) from and monitoring for opiate misuse, diversion, addiction, and symptoms of withdrawal in patients treated frequently with opiates. Tolerance is common in those treated with daily opiates for >1 week and should be expected with appropriate increases in opiate doses if needed.

Hemorrhagic or ischemic stroke historically has occurred in 11% of individuals with SCA before age 20 years.²⁶ Patients typically present with facial droop, hemiparesis, seizure, dysarthria, headache, and/or aphasia.²⁷ Magnetic resonance imaging (MRI) is preferred to demonstrate the changes associated with acute infarction, and MR angiography most often reveals obstruction or stenosis of the internal carotid artery, middle, and/or anterior cerebral artery. Prompt exchange transfusion is the preferred intervention for these patients. Significant and rapid reduction in the hemoglobin S fraction may be more effective in preventing recurrence than simple transfusion to a hemoglobin concentration >10 g/dL while the hemoglobin S is ≥30% increases the viscosity of whole blood.^{28–30 E} After the patient has been stabilized, chronic transfusions to maintain hemoglobin S at ≤30% are instituted as secondary prophylaxis. Approximately 40% of children with ischemic stroke will have moyamoya syndrome, obstruction of the large cerebral arteries with collateral blood vessels that give the appearance of a puff of smoke on conventional angiography.³¹ These children are at a much higher risk of recurrent stroke, and some pediatric hematologists and neurosurgeons recommend revascularization procedures or bone marrow transplantation to decrease this risk.^32–34

Transcranial Doppler is an effective screening tool to identify children at increased risk of stroke and is recommended annually for patients ages 2 to 16 years with SCA.^10,35 Children with elevated cerebral blood flow velocity (>200 cm/second) were randomly assigned to chronic transfusions to decrease hemoglobin S to ≤30% or observation. Chronic transfusions reduced the risk of stroke from 30% to 3% during a 30-month period.³⁶

Central nervous system disease continues to be a problem despite the decreased incidence of large-vessel cerebral infarction with transcranial Doppler screening. Cerebral ischemia detected on MRI without associated neurologic deficit is referred to as silent cerebral infarct (SCI) and is most prevalent in children with SCA, but it also is seen in patients with HbSC and HbSβ⁺. Risk factors for the development of SCI include episodes of acute anemia, chronic anemia <7 g/dL, higher systolic blood pressure, male sex, and internal carotid stenosis.^37–39 SCI has been detected in young children with HbSS, with a reported prevalence ranging from 11% (15 months of age) to 27.7% by 3.4 years^40,41 and from 5% to 13.5% in children with HbSC.^42,43 Prevalence increases with age into adulthood, suggesting ongoing injury. SCI is associated with worse neurocognitive outcomes and increased risk of overt stroke.^44,45 In a controlled multicenter trial, chronic transfusions in patients with SCI were shown to decrease the incidence of new SCI and overt stroke, but no difference in IQ was seen during this 3-year trial.⁴⁶ Based on the results of this study, some SCD experts recommend screening children with SCA at age 5 years for SCI by MRI and for all patients with poor academic performance. Cognitive impairment also is more prevalent in children with SCA and normal brain MRIs compared with their siblings without SCD, and it is associated with more severe anemia, low pulse oximetry, older age, and socioeconomic factors such as head of household education and family income.^47,48

Ophthalmologic Disease

Proliferative retinopathy occurs in children and more often affects patients with HbSC. Annual incidence rates were 0.5 cases (95% confidence interval 0.3– 0.8) per 100 subjects with HbSS and 2.5 cases (95% confidence interval 1.9–3.3) per 100 patients with HbSC in the Jamaican Cohort Study.⁴⁹ The prevalence has been reported to be 45% of patients with HbSC, 11% of patients with HbSS, and 17% of patients with sickle β thalassemia by early adulthood.⁵⁰ Retinal ischemia and neovascularization eventually develop, leading to retinal detachment and loss of visual acuity. Annual dilated ophthalmologic examination is recommended for patients beginning at age 10 years to detect early retinal injury. Ophthalmologic interventions for proliferative retinopathy include laser photocoagulation and vitrectomy in severe cases of vitreous hemorrhage.

Renal Disease

Sickle vasculopathy impairs both renal tubular and glomerular function. Children with SCD commonly have frequent urination and nocturnal enuresis because of their inability to concentrate their urine (hyposthenuria). Maintenance of good hydration is a critical piece of advice for these patients. Screening for microalbuminuria starting at age 10 years may identify patients at increased risk for chronic kidney disease.⁵¹ Children with microalbuminuria or modest elevations in serum creatinine (>0.7 mg/dL) should be referred to a pediatric nephrologist. Renal dysfunction progresses with age manifesting as microalbuminuria, proteinuria, glomerular sclerosis, and, in some patients, chronic renal failure. Proteinuria has been reported in 6.2% to 41%, and chronic kidney disease has been reported in 8% to 26.5% of children; the rate of both conditions increases with age.^51–53 End-stage renal disease occurs in approximately 2% to 4% in adults with SCD^54,55 and was identified as an independent predictor of early mortality.^56,57 Angiotensin-converting enzyme inhibitors are prescribed commonly for their renoprotective effects; Falk et al reported a decline in proteinuria after short-term use of enalapril in a small number of adults with SCD.⁵⁴ Hydroxyurea (HU) may partially preserve concentrating ability and decrease glomerular hypertrophy and hyperfiltration.^58,59

Treatment with HU

HU is the only US Food and Drug Administration–approved disease-modifying therapy for SCD. It is a ribonucleotide reductase antagonist that increases fetal hemoglobin production and total hemoglobin. HU also reduces the neutrophil count and intracellular adhesion and increases nitric oxide bioavailability, which may account for some of the clinical benefits.^60–63 Multiple clinical trials in children and adults have demonstrated the benefits of HU on rates of VOC, ACS, quality of life, hospitalization, and mortality.^64–69 There is no diminution of growth or pubertal development, even after chronic use.^70,71 The pediatric hydroxyurea phase III clinical trial, more commonly known as BABY HUG, established a favorable safety and efficacy profile for HU in children as young as 9 months old.⁷² The main adverse effects of HU for both children and adults include neutropenia, thrombocytopenia, rash, and nail changes.

Based on the NHLBI guidelines published in 2014, children 9 months and older with SCA should be offered HU at a starting dose of 20 mg/kg/day. CBC with differential and reticulocyte count should be monitored every 4 weeks for cytopenias, with a goal absolute neutrophil count of between 2000 and 4000/μL and a platelet count ≥80,000/μL. The dose may be escalated by 5 mg/kg every 8 weeks to the maximum tolerated dose of 35 mg/kg/day based on clinical or laboratory findings. Once the patient is taking a stable dose, laboratory values may be monitored every 2 to 3 months.¹⁰ HU can be considered on a case-by-case basis for patients with HbSC or HbSβ⁺ and moderate to severe symptoms. It is possible that HU could replace chronic transfusions in some patients receiving them for an elevated cerebral blood flow velocity.⁷³

Treatment with Transfusion

Transfusion of sickle-negative red blood cells is an effective treatment for several acute and chronic complications of SCD and includes simple and exchange transfusions. Simple transfusions are indicated in patients with low hemoglobin concentration, because transfusion above a hemoglobin concentration of 10 g/dL with hemoglobin S >30% can cause hyperviscosity and increased vaso-occlusive complications, as well as the following complications: splenic sequestration with severe anemia, moderate ACS, and symptomatic anemia. Either simple or exchange transfusion is effective for hepatic or intrahepatic sequestration, multiorgan failure syndrome, or acute stroke, but exchange transfusion is preferred for these complications if readily available and for severe ACS. Patients receiving chronic transfusion for primary or secondary stroke prophylaxis can be treated with either simple or exchange transfusions. Transfusion, however, is neither necessary nor effective for the treatment of asymptomatic anemia, chronic splenic sequestration, or acute vaso-occlusive pain in children with SCD (Table 2).^F The major risks of transfusion in people with SCD are iron overload and alloimmunization to minor blood group antigens. Iron overload occurs in all patients receiving chronic simple transfusions but only a small proportion of those receiving exchange transfusions.⁷⁴ Alloimmunization to minor antigens on red blood cells occurs in 12% of children and up to 27% of adults and can cause delayed hemolytic transfusion reactions and delays in transfusion secondary to difficulty obtaining compatible units.^75,76 We recommend following a standardized protocol for chronically transfused children with SCD, including monitoring and treating iron overload and phenotypically matched blood for the C, E, and K antigens.

Table 2.

Indications for transfusion from NHLBI Evidence-Based Management of Sickle Cell Disease, Expert Panel Report, 2014

Complication	Transfusion	Strength of recommendation	Evidence
Anemia, asymptomatic	No	Consensus-expert panel
Kidney injury (unless multisystem organ failure)	No	Consensus-expert panel
Pain crisis, uncomplicated	No	Moderate	Low
Priapism	No	Moderate	Low
Splenic sequestration, chronic	No	Low	Low
Splenic sequestration, severe anemia	Simple	Strong	Low
ACS, severe	Exchange	Strong	Low
ACS, moderate	Simple	Moderate	Low
Anemia, symptomatic	Simple	Consensus-expert panel
Aplastic crisis	Simple	Consensus-expert panel
Hepatic sequestration	Eithera	Consensus-expert panel
Intrahepatic sequestration	Either	Consensus-expert panel
Multisystem organ failure	Either	Consensus-expert panel
Stroke, acute	Either	Moderate	Low
Before surgery with general anesthesia	Consult	Moderate to strong	Low
Stroke risk (TCD reading >200 cm/s)	Chronicb	Strong	High
Prior stroke	Chronic	Moderate	Low

ACS, acute chest syndrome; NHLBI, National Heart, Lung, and Blood Institute; TCD, transcranial Doppler.

^aEither indicates either simple or exchange transfusion.

^bChronic, transfusions typically every 4 weeks to maintain a trough HbS <30%.

Conclusions

SCD can cause frequent severe pain and life-threatening complications involving multiorgan systems in children. These complications can be minimized through education and partnership between primary care providers and pediatric hematologists to provide SCD-specific healthcare maintenance. In addition, specific treatments including HU and regular transfusions can prevent many of the complications of SCD, and analgesics, antibiotics, and blood transfusion are needed frequently as treatments for acute complications. Useful resources for providers of care to people with SCD include the National Heart, Lung, and Blood Institute's Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014 and the American Society of Hematology's sickle cell pocket guides and smartphone app based on this report.^11,77–79

Table 1.

Healthcare maintenance in SCD

Complication	Preventive measure	Genotype	Age to start	Frequency
Pneumococcal sepsis	Penicillin 125 mg when <3 y old, 250 mg when ≥3 y old	All	Upon diagnosis	Twice daily until ≥5 y old
	Prevnar-13 series	All	2 mo	Per infant vaccine schedule
	Pneumovax-23	All	2 y	Once at 2 y old, second booster 3–5 y later
Meningococcal disease	Hib-MenCY-TT or equivalent Meningococcal polysaccharide	All	2 mo 2 y	2, 4, 6, and 12–15 mo 2 boosters separated by 8–12 wk, then every 5 y thereafter
Stroke	Transcranial Doppler	HbSS, HbSβ0 thalassemia	2 y	Annually
Retinopathy	Dilated retinal examination	All	10 y	Annually
Nephropathy	Urinalysis with microscopicA	All	10 y	Annually

Hib-MenCY-TT, Haemophilus b tetanus toxoid conjugate vaccine; SCD, sickle cell disease.

^AWith microscopic what?

Key Points.

• Regular healthcare maintenance and ongoing education of the family and patient are critical for the prevention of long-term morbidity in pediatric patients with sickle cell disease (SCD).

• Evidence-based interventions such as hydroxyurea and transfusions can prevent some of the significant complications of SCD.

• Physicians in many different disciplines may care for these children; therefore, awareness of the complications of SCD and partnership with pediatric hematologists will help ensure good outcomes.