health maintenance and education for children and adults · adams rj, brambilla d. discontinuing...
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Health Maintenance and Education for Children and Adults
Richard Ward, MSc, MRCP, FRCPath Director, Red Blood Cell Disorders Program, UHN
Assistant Professor, Hematology, University of Toronto Chair, Canadian Hemoglobinopathy Association
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Objectives
1. What are the key aspects of managing a patient with sickle cell disease across their lifespan?
2. What complications should I be aware of and how do I manage them?
3. How can services best be developed for patients with SCD?
• Infections in childhood, and beyond
• Wellness and health maintenance surveillance
• Multidisciplinary teamwork
• Chronic pain management
• Stroke prevention and iron overload strategies
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SCD Then and Now
Quinn, et al., Blood 2010
High rate of childhood death
from infections
>10% children suffer a stroke,
25% of adults
=NBS!
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What are the vaso-occlusive manifestations of SCD?
Vaso-occlusive Pain Stroke
Acute Chest Syndrome Avascular necrosis Functional asplenia
Hepatic sequestration Retinopathy
Gladwin et al, NEJM 2008
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What are the hemolytic manifestations of SCD?
Anemia Pulmonary Hypertension
Leg Ulcers Priapism
Cerebral Vasculopathy Cholelithiasis
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What are the infectious manifestations of SCD?
Viral induced aplastic anemia Infection from encapsulated organisms:
Pneumonia Meningitis
S. pneumonia, H. influenzae, N. meningitides Septic Arthritis or Osteomyelitis: (Salmonella common organism)
Urinary tract Infection
Gladwin et al, NEJM 2008
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Sickle Cell Disease is for Life
?
Definition of “for life” has changed
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Detect and Prevent/Treat SCD Morbidity
SCD is a poster child
for multisystem
diseases
Brain Eyes Tonsils Lungs Heart Kidneys Fertility Liver Spleen Skin Bones
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21st Century Goals of Care for SCD
Patient self-management Reduced hospital dependence
Social, financial and emotional wellbeing
Monitoring and treatment of complications
Normal life expectancy
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Therapeutic Tools at Our Disposal
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Multidisciplinary Team • Nurse Practitioners
• Social Worker
• Physicians
– Trainees
• Administrative
– Nursing Manager
– Clerical
– Data Manager
• Medical Day Unit
– Nursing Team
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: uhn rbcd
Collaboration
• Combined cardiac • Combined endocrine
• Neurology • Ophthalmology • Nephrology • Urology • Obstetric • Infectious Diseases • ……… • Community partners
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Assessment of New Referral #1 • Up to date contact info and list of providers
• Acute complications (pain)
– Analgesia use
• Chronic morbidity (head to toe)
• Red flags
– Acute Chest Syndrome
– Stroke
– ICU admission
– Exchange transfusion
• Therapies
– Hydroxyurea
– Transfusions +/- chelation
• Socio-economic history
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Assessment of New Referral #2 • Investigations
– Labs, Urinalysis
– ECHO, ECG
– Bone mineral density scan
– MRI brain +/- Liver MRI for LIC
• Therapies
– Immunisations
– Analgesia
– Hydroxyurea
– Transfusions +/- chelation
Follow-Up q1w – q6m
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Neurological Events in SCD
Overt Stroke
Silent Cerebral Infarct
Moyamoya
TIA
Vasculopathy
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Effects of Silent Infarcts and Stroke on Cognitive Function
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Stroke type and prevalence differ between pediatric and adult population
Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. 1998 Jan 1;91(1):288-94.
Infarctive
Hemorrhagic
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Early Detection of Increased Risk for Stroke
Transcranial Doppler (TCD)
• Measures peak velocity blood flow in MCA by ultrasound
• High velocity = stenosis and vasculopathy
• > 170 cm/s (conditional) • > 200 cm/s (abnormal) • associated with 40%
risk of stroke within 3 years
Adams RJ. Big strokes in small persons. Arch Neurol. 2007 Nov;64(11):1567-74
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STOP Study Results
Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998 Jul 2;339(1):5-11
Study or Subgroup
Adams 1998
Total (95% CI)
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 2.56 (P = 0.01)
Events
1
1
Total
63
63
Events
11
11
Total
56
56
Weight
100.0%
100.0%
M-H, Fixed, 95% CI
0.07 [0.01, 0.53]
0.07 [0.01, 0.53]
Transfusion No Transfusion Odds Ratio Odds Ratio
M-H, Fixed, 95% CI
0.01 0.1 1 10 100
Favours transfusion Favours no transfusion
• RR = 0.097
• ARR = 0.015
• RRR = 0.903
• NNT = 6.7
Other NNTs for Comparisons
• Compression stockings prevent VTE
• 9 (7 – 13)
• Anti-hypertensives preventing CV
• 18 (14 – 25)
• ASA preventing CV death post-MI
• 40
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STOP2 Study Results
Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. The New England journal of medicine 2005;353(26):2769-78
Study or Subgroup
Adams 2005
Total (95% CI)
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 2.68 (P = 0.007)
Events
0
0
Total
38
38
Events
16
16
Total
41
41
Weight
100.0%
100.0%
M-H, Fixed, 95% CI
0.02 [0.00, 0.35]
0.02 [0.00, 0.35]
Continued Transfusion Transfusion Halted Odds Ratio Odds Ratio
M-H, Fixed, 95% CI
0.01 0.1 1 10 100
Favours Transfusion Favours No Transfusion
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SWiTCH Study Results
• No difference in LIC
Hydroxyurea + Phlebotomy
(N = 67)
Transfusion + Chelation
(N = 66)
P value
Median 17.2 17.3 0.7920
IQR 10.0 – 30.6 8.8 – 30.7
* Wilcoxon rank sum test due to non-normal distribution of LIC
Study or Subgroup
Ware 2011
Total (95% CI)
Total events
Heterogeneity: Not applicable
Test for overall effect: Z = 1.90 (P = 0.06)
Events
7
7
Total
67
67
Events
0
0
Total
66
66
Weight
100.0%
100.0%
M-H, Fixed, 95% CI
16.49 [0.92, 294.84]
16.49 [0.92, 294.84]
Hydroxyurea + Phlebotomy Transfusion + Chelation Odds Ratio Odds Ratio
M-H, Fixed, 95% CI
0.01 0.1 1 10 100Hydroxyurea + Phlebotomy Transfusion + Chelation
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1. Increase in HbF production; 2-3. Decrease in White Blood Cell numbers and stickiness; 4. Stops dehydration of RBCs; 5. Helps mop up toxins from breakdown of RBCs
Hydroxyurea Mode of Action
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Development of Hydroxyurea
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Charache, S., et al. (1995). NEJM 332(20): 1317-1322
Mulitcentre Study of Hydroxyurea, 1995
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Indications for Hydroxyurea • Classical (MSH Study)
>3 pain episodes / yr >1 ACS
• Current All patients with HbSS - Prevention of end-organ damage / survival benefit
HbSC with high HbF, low HCT and symptoms Jehovah’s Witnesses
• Dosing To maximum tolerated dose Monthly reviews whilst titrating
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Side Effects/Concerns
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Gluckman, Hematology ASH Education Book, 2013
Curative Therapies