Sickle Cell Disease: New Approaches and Guidelines
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Transcript Sickle Cell Disease: New Approaches and Guidelines
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
Provide basic overview of Sickle Cell Disease
Understand recommendations for care based on
2014 NHLBI guidelines
Health Maintenance
Acute Problems
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)
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
Brief Pathophysiology
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
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
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
General co-morbidities to address and control
Asthma
Obstructive Sleep Apnea
Dental Caries
Screen for retinopathy/retinal infarct
By history (age 0-2 yrs)
By vision screen (3-10yrs)
By comprehensive eye exam (10 yrs+)
Screen for renal disease
Proteinuria starting age 10y
Routine Health Maintenance
Screen for CNS problems (strokes, moyamoya)
Annual Trans-Cranial Doppler (2-16y) for HbSS/HbSb0
By specialist
History of neurocognitive symptoms/decline (headaches,
changes in school or work performance)
No longer routine Pulmonary Hypertension Screen
(EKG, ECHO, CXR)
Anticipatory guidance to include risk of priapism
Routine Health Maintenance
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
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
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
Consider in other populations (e.g. SCD and
chronic kidney disease, HbSβ+thal/HbSC and
recurrent painful crises)
Initiation and Monitoring
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
Maximum tolerated dose to keep
ANC >2,000/µL– 4,000/µL
Platelets >80,000
ARC >80,000
Initiation and Monitoring
Initiation and titrating typically done by specialist
Monitoring could be done in collaboration with
PCP, if more accessible for the patient
Similar to anti-convulsant levels and titrating
Reproductive Counseling
Discuss importance of knowing partners’
hemoglobin genotype for genetic counseling
Hydroxyurea (HU) is a teratogen
Long Acting Reversible Contraceptive (LARC) is
recommended while on HU
Progesterone-only contraception may be
preferable
Current recommendation is to discontinue HU
before pregnancy and while breastfeeding
Acute and Chronic Problems
Fever
Respiratory Symptoms
Anemia
Neurological Symptoms
Pain
Management of Fever in SCD
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
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
Acute focal neurological deficits
Risk of acute stroke
Immediate, emergency evaluation and treatment
Headaches
Risk of Moyamoya - Stenotic arteries in Circle of
Willis/basal ganglia with network of collaterals
(“puff of smoke”)
Referral to specialist
Neurological Symptoms
“Silent” Cerebral Infarcts
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’
Most prominent manifestation
Variable frequency (none to daily)
May be precipitated by illnesses, stress,
dehydration
Pain in the extremities, Headache, Chest,
Abdomen
Abdominal pain may mimic surgical condition
Acute/Vaso-occlusive
Assess for other complications (e.g. aplastic
crisis, neuro event, priapism, sepsis, fever,
ACSD, abdominal, ortho, etc)
Keep warm, hydrated
Assure following home pain plan
Home plan fails → emergency treatment
Chronic Pain
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
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