Chronic transfusion practices for prevention of primary stroke in children with sickle cell anemia and abnormal TCD velocities

Abstract

; for the TCD With Transfusions Changing to Hydroxyurea (TWiTCH) Trial Investigators Chronic transfusions are recommended for children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities ( 200 cm/sec) to help prevent the occurrence of a primary stroke [1]. The goal is usually to maintain the sickle hemoglobin concentration (HbS) <30%; however, this goal is often difficult to achieve in clinical practice. The NHLBI-sponsored trial ''TCD With Transfusions Changing to Hydroxyurea (TWiTCH)'' will compare standard therapy (transfusions) to alternative therapy (hydroxyurea) for the reduction of primary stroke risk in this patient population. Transfusions will be given according to current transfusion practices at participating sites. To determine current academic community standards for primary stroke prophylaxis in children with SCA, 32 clinical sites collected data on 340 children with abnormal TCD velocities receiving chronic transfusions to help prevent primary stroke. The average (mean ± 1 SD) pretransfusion HbS was 34 ± 11% (institutional average 23-48%); the 75th and 90th percentiles were 41 and 50%, respectively. Lower %HbS was associated with higher pretransfusion Hb values and receiving transfusions on time. These data indicate variable current transfusion practices among academic pediatric institutions and in practice, 30% HbS may not be an easily attainable goal in this cohort of children with SCA and abnormal TCD.Children with sickle cell anemia (SCA) compose a high risk group for the development of stroke. If untreated, 11% will experience a clinical stroke by 20 years of age [2]. Adams et al. have shown that children with SCA who are at risk for primary stroke can be identified by measuring time-averaged mean blood flow velocities in the internal carotid or middle cerebral arteries by TCD [3]. Abnormal TCD velocities ( 200 cm/sec) are associated with high risk for stroke and warrant transfusion therapy to reduce the risk of primary stroke. First stroke can be successfully prevented in 90% of children with SCA and abnormal TCD velocities by the use of chronic transfusion therapy, with a goal of keeping HbS concentrations less than 30% [1].TCD with Transfusions Changing to Hydroxyurea (TWiTCH) is an NHLBIsponsored, Phase III, multicenter trial comparing standard therapy (monthly transfusions) to alternative therapy (daily hydroxyurea) to reduce the risk of primary stroke in children with SCA and documented abnormal TCD velocities. Since transfusions compose the standard treatment arm, accurate %HbS values achieved in actual clinical practice were needed for protocol development. The majority of our information about transfusing patients with SCA to prevent stroke comes from secondary stroke prevention, i.e., the use of chronic red blood cell transfusions to prevent a second stroke after a first clinical stroke has occurred. Classically, transfusions are administered at 4-week intervals to maintain HbS at less than 30%. After several years of transfusion therapy, a few centers ...

The burden of sickle cell disease in Cape Town

“…This strategy is known to reduce stroke episodes. 17 The absence of any SCD-related mortality must be interpreted with caution. A retrospective cross-sectional hospital-based study may miss children with severe disease who have died in early childhood, and there may be individuals who have a mild disease phenotype and are never diagnosed.…”

A comparison of chronic manual and automated red blood cell exchange transfusion in sickle cell disease patients

“…However, a large number of subjects in both cohorts were not able to achieve their prescribed target. Published literature has shown that the ability to achieve the requisite pre‐RBCX HbS/SC target can be quite variable (Aygun et al , ; Ware & Helms, ). The evidence for the chosen pre‐RBCX HbS/SC target of <30% was largely derived from the STOP (Stroke Prevention in Sickle Cell Anaemia) and STOP2 trials (Adams et al , ; Adams & Brambilla, ), the SWiTCH (Stroke With Transfusions Changing to Hydroxyurea) trial (Ware & Helms, ) and retrospective data (Pegelow et al , ).…”

Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial

“…The study inclusion criteria included: patients with SCA, age range 5.0-18.9 years at enrollment; previous completed overt clinical (index) stroke after age 1 year with central confirmation; $18 months of erythrocyte transfusions since the index stroke; transfusional iron overload with liver iron concentration $5.0 mg of iron/gram of dry weight liver or serum ferritin $500 ng/mL on 2 independent measurements; and adequate monthly erythrocyte transfusions with average HbS #45% for the past 6 months before enrollment. 25 Recognizing that the use of aspirin for secondary stroke prophylaxis varied among academic centers, the SWiTCH protocol neither recommended nor prohibited its use. A total of 161 subjects enrolled in the SWiTCH trial; 150 and 146 with entry brain MRI/MRA and TCD examinations during the initial screening period, respectively.…”