Monitoring of treatment in sickle cell anemia - PowerPoint Presentation

Slide1

Monitoring of treatment in sickle cell anemia

Mohammadreza

Bordbar

, MD

Pediatric Hematologist

Associate professor of SUMS

Qeshm

island, 22

feb

2018

Slide2

Introduction

Care for persons with SCD often lacks continuityTwo SCD-specific disease-modifying treatments (HU, blood transfusion) still underutilizedUp-to-date clinical guidelines is a necessityNIH-sponsored SCD guidelines, “Evidence-Based Management of Sickle Cell Disease, Expert Panel Report 2014”

JAMA. 2014;312(10):1033-1048Am Fam Physician. 2015;92(12):1069-1076

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Health maintenance

Prevention of invasive pneumococcal infection - oral penicillin prophylaxis at least up to age of 5 years - beyond the age of 5 if splenectomy or invasive pneumococcal infection - complete pneumococcal vaccination before discontinuation - at least 1 dose of PCV-13 in children 6-18 years with functional or anatomic asplenia

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Screening for hepatitis C

Screen in patients at high risk for infection (multiple transfusion)

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Screening for retinopathy

Dilated eye examination since the age of 10 yearsRescreen every 1-2 years if NL exam

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Screening for risk of stroke

Screen with TCD annually starting at age 2 till the age of 16 yearsConsider regular transfusion in those with conditional (170-199cm/s) or elevated (≥200cm/s) TCDIn asymptomatic children with SCD, no need for MRI or CTIn asymptomatic adults with SCD, no need for TCD or MRI/CTDo not screen children with other SCD (S/β+ -thalassemia, HbSC)

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Cardiovascular/ pulmonary screening

No need for ECG screening in asymptomatic children or adults

No need for PFT in asymptomatic children or adults

Doppler echocardiography, NT-pro-BNP, Right heart catheterization (RHC) in symptomatic patients for screening pulmonary hypertension

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American thoracic society clinical practice guideline

Increased risk of mortality:Tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/secondNT-pro-BNP ≥ 160 pg/mlRHC-confirmed PH (resting mean PAP ≥ 25 mm Hg)

Am J Respir Crit Care Med. 2014 Mar 15; 189(6): 727–740.

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Proposed algorithm for evaluation of pulmonary hypertension in SCD

Am J

Respir

Crit

Care Med. 2014 Mar 15; 189(6): 727–740

.

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Managing chronic complications

Avascular necrosis:

- if intermittent or chronic hip pain, evaluate for AVN by

Hx

, PE, radiography

and MRI as needed

- treat with analgesics

- consult with physical therapy and orthopedic department

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Renal complications

Regular assessment of creatinine, GFR

Screen annually for proteinuria with spot urine test since the age of 10 years

If proteinuria > 300mg/24

hr

, refer to a nephrologist for further evaluation

Initiate ACE inhibitor in adults with microalbuminuria or proteinuria without other apparent cause even with NL BP

Renal replacement therapy (dialysis, transplantation) if needed

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Leg ulcers

Standard therapy (debridement, wet to dry dressing, topical agents)

Evaluate for osteomyelitis in chronic recalcitrant deep leg ulcers

Treat with local or systemic antibiotics if suspicious for infection and positive wound culture

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Evidence-based recommendations for use of hydroxyurea therapy

JAMA. 2014;312(10):1033-1048

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Adults with ≥3 moderate to severe pain crisis during a 12-mo period

Pains interfering with daily activities and QOLSevere or recurrent ACSSevere symptomatic chronic anemia interfering with daily activities or QOLAdults and children with chronic kidney disease taking EPO to improve anemiaInfants 9 mo or older, children and adolescents regardless of clinical severity to reduce complications (dactylitis, pain, ACS, anemia)Discontinue in pregnant or breastfeeding women

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Monitoring HU therapy

Laboratory tests before starting therapy:

- CBC, diff;

Retic

count

- quantitative

Hb

F measurement

- renal and liver function tests

- pregnancy test for women

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Initiating HU therapy

Baseline elevation of

Hb

F should not affect the decision to initiate HU

Counselling regarding contraception in both genders

o

f reproductive age

Starting dose for adults:

15mg/kg/d

round up to the nearest 500mg

5-10 mg/kg/d in adults with chronic kidney disease

Starting dose for infants & children:

20mg/kg/d

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Monitoring hu therapy

CBC, diff &

R

etic

count every 4wks when adjusting dosage

Aim for a target

ANC≥2000/µl

Younger persons with lower baseline counts may safely tolerate ANC down to

1250/µl

Maintain

platelet ≥ 80,000/µl

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If neutropenia or thrombocytopenia occurs

Stop HU temporarily

Monitor CBC, diff weekly

Restart HU at a dose 5mg/kg/d lower dose when

cytopenia

recovered

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Dose escalation

Increase by

5mg/kg/d

every 8wk

Give until mild myelosuppression (ANC 2000-4000/µl) up to a maximum dose

35mg/kg/d

CBC, diff &

Retic

count every 2-3

mo

once stable dose established

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Evidence-based recommendations for use of transfusion therapy

JAMA. 2014;312(10):1033-1048

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Symptomatic severe ACS (O2 saturation <90% despite supplemental O2)

Symptomatic ACS and ↓Hb˃ 1g/dL from baseline (if baseline Hb˂ 9g/dL)Acute splenic sequestration plus severe anemiaAcute strokeHepatic sequestrationIntrahepatic cholestasisMultisystem organ failureAplastic crisisSymptomatic anemiaChild with TCD≥ 200cm/sAdults and children with previous clinically overt stroke

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Simple vs exchange transfusion

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Evidence-based recommendations against use of transfusion

Uncomplicated painful crisisPriapismAsymptomatic anemiaAcute kidney injury without multi-organ failureRecurrent splenic sequestration

JAMA. 2014;312(10):1033-1048

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Precautions and monitoring

RBC phenotype matching to at least C, E, K antigensMonitor for delayed transfusion reactionsMonitoring serum ferritin quarterlyT2* MRI (the optimal frequency of assessment not established)Iron chelation if confirmed iron-overload (LIC ≥ 7mg Fe/g dry weight)

Med

Clin

N Am 101 (2017) 375–393

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A summary of clinical trials in SCD (primary prevention of life-threatening infections)

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primary & secondary prevention of stroke

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hsct

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Evidence-based strong recommendations with high-quality evidence (JAMA. 2014;312(10):1033-1048)

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Thanks for your attention