Sickle Cell Disease: New
Approaches and Guidelines
Developed as part of a collaboration of CCNC, the NC
Division of Public Health, the comprehensive sickle cell
centers at Carolinas Health Care, Duke University, East
Carolina University, University of North Carolina at Chapel
Hill, Mission, and Wake Forest University and primary care
physicians across North Carolina. Adapted from the NIHLBI
guidelines
Objectives
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Provide basic overview of Sickle Cell Disease
Understand recommendations for care based on
2014 NHLBI guidelines
Health Maintenance
 Acute Problems
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Introduce tools to facilitate adoption of
recommendations
Foster specialist and primary care collaboration
in care of patients with sickle cell disease
Sickle Cell Disease (SCD)
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SCD refers to a group of disorders characterized by
a predominance of HbS
SCD affects 1 in 375 African American live births,
as well as other populations
Includes HbSS, HbSC, HbS/b thalassemia (b0b+),
HbS/Other
Sickle Cell Anemia (SCA)
Subset of genotypes with often more clinical severity
and anemia
 Includes HbSS, HbS/b0thalassemia
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Brief Pathophysiology
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Mutation at sixth position of beta
globin chain changes glu → val
With deoxygenation, the HbS molecule
polymerizes within the RBC leading to
characteristic shape changes
Sickled erythrocytes are rigid and
obstruct small blood vessels leading to
tissue ischemia
Deformed sickle cells adhere to
endothelium & macrophages
 induces hemolytic process
Inflammation and ongoing adhesion
Manifestations of
Sickle Cell Disease
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Chronic anemia
 Hemolysis
 Jaundice
 Cholelithiasis (bilirubinate)
Acute complications
 Pain, priapism, stroke
 Acute chest syndrome (ACS)
 Splenic sequestration
 infection
Chronic organ damage
 Spleen, brain
 Kidneys, lung, bones, eyes
pulmonary
HTN
gallstones
anemia
Hemolysis
leg ulcers
nephropathy
AVN
Vaso-Occlusion
asplenia
ACS
stroke
pain
Recommendations and Tools
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Health Maintenance
 Pediatric and Adult
Problem-focused– Acute and Chronic
 Fever
 Respiratory Symptoms/Hypoxia
 Anemia
 Neurological
 Pain
Tip Sheet - New Recommendations and Clinical
Pearls
Health Maintenance
Routine Health Maintenance
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General co-morbidities to address and control
Asthma
 Obstructive Sleep Apnea
 Dental Caries
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Screen for retinopathy/retinal infarct
By history (age 0-2 yrs)
 By vision screen (3-10yrs)
 By comprehensive eye exam (10 yrs+)
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Screen for renal disease
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Proteinuria starting age 10y
Routine Health Maintenance
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Screen for CNS problems (strokes, moyamoya)
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Annual Trans-Cranial Doppler (2-16y) for HbSS/HbSb0
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By specialist
History of neurocognitive symptoms/decline (headaches,
changes in school or work performance)
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No longer routine Pulmonary Hypertension Screen
(EKG, ECHO, CXR)
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Anticipatory guidance to include risk of priapism
Routine Health Maintenance
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PenVK 125mg BID <3y; 250mg BID >3y
Until age 5 yrs for HbSS/Sb0, if no splenectomy or
invasive bacterial infection
 Typically to age 3 yrs for other genotypes, but weak
recommendation to consider no prophylaxis
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13-valent pneumococcal vaccine (Prevnar) as per
recommendations for general population
23-valent pneumococcal age 2 and 7 years
MenHibRix or Menveo at 2, 4, 6, and 12-15 months
MCV4/Menactra – 2 dose primer at age 2, booster
at age 5, and then every 5 years
Routine Health Maintenance
Hydroxyurea (HU)
 Original use – anti-cancer drug
 Increases fetal hemoglobin in the blood
 Prevents sickling of red cells
 RBCs survive longer in the bloodstream
 Daily doses reduce:
 Frequency of painful crises
 Frequency of acute chest syndrome
 Need for blood transfusions/severe anemia
 Mortality
Effects of Hydroxyurea in SCA
Expanded Recommendations for
Hydroxyurea
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ALL children > 9 months with SCA (HbSS,
HbSb0thal)
Adults with SCA:
3+ painful crises in 12 months
 Sickle cell pain or severe symptomatic chronic anemia
that interferes with daily activities or quality of life
 History of ACS
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Consider in other populations (e.g. SCD and
chronic kidney disease, HbSβ+thal/HbSC and
recurrent painful crises)
Initiation and Monitoring
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Starting dose
Children - 20 mg/kg/day
 Adults - 15 mg/kd/day (5-10 mg/kg/day if CKD)
 Increase by 5 mg/kg/day q8w to maximal tolerated
dose (max 30-35 mg/kg/day)
 Monitor CBC, reticulocyte count every 4 weeks during
initiation and every 3 months while on a stable dose
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Maximum tolerated dose to keep
ANC >2,000/µL– 4,000/µL
 Platelets >80,000
 ARC >80,000
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Initiation and Monitoring
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Initiation and titrating typically done by specialist
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Monitoring could be done in collaboration with
PCP, if more accessible for the patient
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Similar to anti-convulsant levels and titrating
Reproductive Counseling
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Discuss importance of knowing partners’
hemoglobin genotype for genetic counseling
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Hydroxyurea (HU) is a teratogen
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Long Acting Reversible Contraceptive (LARC) is
recommended while on HU
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Progesterone-only contraception may be
preferable
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Current recommendation is to discontinue HU
before pregnancy and while breastfeeding
Acute and Chronic Problems
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Fever
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Respiratory Symptoms
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Anemia
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Neurological Symptoms
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Pain
Management of Fever in SCD
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Prompt evaluation for any fever > 38.5°C (101.3°F)
 Age < 1 year (any fever > 38°C (100.5°F)
 CBC, Blood Culture, retic, ± CXR ± Ucx
 Immediate administration of IV/IM Ceftriaxone
Recommend hospital admission for:
 Age < 1 year
 Temp > 39.5°C, 103.1°F
 Allergy to Cephalosporins
 Surgical splenectomy/history of pneumococcal sepsis
 Unsure follow-up
 Toxic appearance, low BP
 Infiltrate on CXR
 WBC < 2000, > 30,000 x 109/L
 Hb < 2 g/dl from baseline or < 6g/dl
Respiratory Symptoms
Biggest worry-Acute Chest Syndrome
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Number One cause of death
Any new infiltrate with
clinical symptoms (e.g. fever,
dyspnea, chest pain, hypoxia,
increased WBC)
CXR may be negative in first
24 hours
Lower lobes most commonly
involved; 1/3 bilateral
May be caused by infection,
sickling, fat embolism,
atelectasis
Neurological Symptoms
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Acute focal neurological deficits
Risk of acute stroke
 Immediate, emergency evaluation and treatment
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Headaches
Risk of Moyamoya - Stenotic arteries in Circle of
Willis/basal ganglia with network of collaterals
(“puff of smoke”)
 Referral to specialist
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Neurological Symptoms
“Silent” Cerebral Infarcts
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Cerebral ischemia on MRI without focal
neurological symptoms
20-30% patients with HbSS
Associated with neurocognitive deficits/decline
Increased risk of overt stroke
Progression shown to be decreased with chronic
transfusion therapy
Consider referrals for neuro/neuropsych/sickle
cell specialist/learning eval/IEP
Pegelow Blood, 2002; Kwiatkowski BJH 2009; DeBaun Blood, 2012
Pain
Acute
Chronic
Acute Painful/
Vaso-occlusive ‘crisis’
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Most prominent manifestation
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Variable frequency (none to daily)
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May be precipitated by illnesses, stress,
dehydration
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Pain in the extremities, Headache, Chest,
Abdomen
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Abdominal pain may mimic surgical condition
Acute/Vaso-occlusive
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Assess for other complications (e.g. aplastic
crisis, neuro event, priapism, sepsis, fever,
ACSD, abdominal, ortho, etc)
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Keep warm, hydrated
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Assure following home pain plan
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Home plan fails → emergency treatment
Chronic Pain
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Major Causes – Avascular necrosis of hips/shoulders, leg
ulcers, chronic bony pain, priapism, neuropathic
pain/hyperalgesia
Assess effect on activity, functional status, quality of life,
depression
Involve pain management specialist, sickle cell provider,
ortho as indicated
Controlled, coordinated pain management
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Best if one provider manages chronic pain medications
Pain Agreement
Check CSRS/Provider Portal for medication/prescriber
history
Thank you
Acknowledgment for part of slide content:
Jennifer Rothman, MD
Director, Pediatric Comprehensive Sickle Cell Program,
Duke University Medical Center