1. 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

2. 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

3. 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

4. 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

5. 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
gall- stones
anemia
Hemolysis
leg ulcers
nephropathy
AVN
The manifestations of SCD are summarized here.
Chronic anemia is the results of hemolysis and this produces jaundice and a tendency to form bilirubinate gall stones.
There are a number of acute complications, such as pain, stroke, and ACS.
Then there is the consequent chronic damage, such as asplenia,nephropathy, and retinopathy.
You can think about the complications of SCD as being primarily due to hemolysis, vaso-occlusion, or a combination of both.
Vaso-Occlusion
asplenia
stroke
ACS
pain 5

7. 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

8. Health Maintenance

9. 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

10. 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

11. 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 months
MCV4/Menactra – 2 dose primer at age 2, booster at age 5, and then every 5 years

12. 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 12

13. Effects of Hydroxyurea in SCA

14. 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)

15. 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 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

16. 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

17. 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

22. Acute and Chronic Problems
Fever
Respiratory Symptoms
Anemia
Neurological Symptoms
Pain

23. 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

26. 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

29. 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

30. 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

32. Pain Acute Chronic

33. 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

34. 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

35. 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

37. Acknowledgment for part of slide content:
Thank you
Acknowledgment for part of slide content:
Jennifer Rothman, MD
Director, Pediatric Comprehensive Sickle Cell Program, Duke University Medical Center