1. Monitoring of treatment in sickle cell anemia
Mohammadreza Bordbar, MD
Pediatric Hematologist
Associate professor of SUMS
Qeshm island, 22 feb 2018

2. Introduction JAMA. 2014;312(10):1033-1048
Care for persons with SCD often lacks continuity
Two SCD-specific disease-modifying treatments (HU, blood transfusion) still underutilized
Up-to-date clinical guidelines is a necessity
NIH-sponsored SCD guidelines, “Evidence-Based Management of Sickle Cell Disease, Expert Panel Report 2014”
JAMA. 2014;312(10):
Am Fam Physician. 2015;92(12):

3. 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

4. Screening for hepatitis C
Screen in patients at high risk for infection (multiple transfusion)

5. Screening for retinopathy
Dilated eye examination since the age of 10 years
Rescreen every 1-2 years if NL exam

6. Screening for risk of stroke
Screen with TCD annually starting at age 2 till
the age of 16 years
Consider regular transfusion in those with conditional
( cm/s) or elevated (≥200cm/s) TCD
In asymptomatic children with SCD, no need for MRI or CT
In asymptomatic adults with SCD, no need for TCD or MRI/CT
Do not screen children with other SCD (S/β+ -thalassemia, HbSC)

7. 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

8. American thoracic society clinical practice guideline
Increased risk of mortality:
Tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/second
NT-pro-BNP ≥ 160 pg/ml
RHC-confirmed PH (resting mean PAP ≥ 25 mm Hg)
Am J Respir Crit Care Med Mar 15; 189(6): 727–740.

9. Proposed algorithm for evaluation of pulmonary hypertension in SCD
Am J Respir Crit Care Med Mar 15; 189(6): 727–740.

10. 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

11. 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

12. 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

13. Evidence-based recommendations for use of hydroxyurea therapy
JAMA. 2014;312(10):

14. Adults with ≥3 moderate to severe pain crisis during a 12-mo period
Pains interfering with daily activities and QOL
Severe or recurrent ACS
Severe symptomatic chronic anemia interfering with daily activities or QOL
Adults and children with chronic kidney disease taking EPO to improve anemia
Infants 9 mo or older, children and adolescents regardless of clinical severity to reduce complications (dactylitis, pain, ACS, anemia)
Discontinue in pregnant or breastfeeding women

15. 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

16. Initiating HU therapy
Baseline elevation of Hb F should not affect the decision to initiate HU
Counselling regarding contraception in both genders of 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

17. Monitoring hu therapy
CBC, diff & Retic 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

18. 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

19. Dose escalation Increase by 5mg/kg/d every 8wk
Give until mild myelosuppression (ANC /µl) up to a maximum dose 35mg/kg/d
CBC, diff & Retic count every 2-3 mo once stable dose established

20. Evidence-based recommendations for use of transfusion therapy
JAMA. 2014;312(10):

21. 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 anemia
Acute stroke
Hepatic sequestration
Intrahepatic cholestasis
Multisystem organ failure
Aplastic crisis
Symptomatic anemia
Child with TCD≥ 200cm/s
Adults and children with previous clinically overt stroke

22. Simple vs exchange transfusion

23. Evidence-based recommendations against use of transfusion
Uncomplicated painful crisis
Priapism
Asymptomatic anemia
Acute kidney injury without multi-organ failure
Recurrent splenic sequestration
JAMA. 2014;312(10):

24. Precautions and monitoring
RBC phenotype matching to at least C, E, K antigens
Monitor for delayed transfusion reactions
Monitoring serum ferritin quarterly
T2* 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

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

26. primary & secondary prevention of stroke

27. hsct

28. Evidence-based strong recommendations with high-quality evidence (JAMA

29. Thanks for your attention