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

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

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!

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

What are the hemolytic manifestations of SCD?

Anemia Pulmonary Hypertension

Leg Ulcers Priapism

Cerebral Vasculopathy Cholelithiasis

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

Sickle Cell Disease is for Life

?

Definition of “for life” has changed

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

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

Therapeutic Tools at Our Disposal

Multidisciplinary Team • Nurse Practitioners

• Social Worker

• Physicians

– Trainees

• Administrative

– Nursing Manager

– Clerical

– Data Manager

• Medical Day Unit

– Nursing Team

: uhn rbcd

Collaboration

• Combined cardiac • Combined endocrine

• Neurology • Ophthalmology • Nephrology • Urology • Obstetric • Infectious Diseases • ……… • Community partners

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

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

Neurological Events in SCD

Overt Stroke

Silent Cerebral Infarct

Moyamoya

TIA

Vasculopathy

Effects of Silent Infarcts and Stroke on Cognitive Function

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

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

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

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

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

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

Development of Hydroxyurea

Charache, S., et al. (1995). NEJM 332(20): 1317-1322

Mulitcentre Study of Hydroxyurea, 1995

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

Side Effects/Concerns

Gluckman, Hematology ASH Education Book, 2013

Curative Therapies