Monitoring of treatment in sickle cell anemia Mohammadreza Bordbar, MD Pediatric Hematologist Associate professor of SUMS Qeshm island, 22 feb 2018
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):1033-1048 Am Fam Physician. 2015;92(12):1069-1076
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
Screening for hepatitis C Screen in patients at high risk for infection (multiple transfusion)
Screening for retinopathy Dilated eye examination since the age of 10 years Rescreen every 1-2 years if NL exam
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 (170-199cm/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)
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
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. 2014 Mar 15; 189(6): 727–740.
Proposed algorithm for evaluation of pulmonary hypertension in SCD Am J Respir Crit Care Med. 2014 Mar 15; 189(6): 727–740.
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
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
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
Evidence-based recommendations for use of hydroxyurea therapy JAMA. 2014;312(10):1033-1048
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
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
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
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
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
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
Evidence-based recommendations for use of transfusion therapy JAMA. 2014;312(10):1033-1048
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
Simple vs exchange transfusion
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):1033-1048
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
A summary of clinical trials in SCD (primary prevention of life-threatening infections)
primary & secondary prevention of stroke
hsct
Evidence-based strong recommendations with high-quality evidence (JAMA
Thanks for your attention