Academic Community Standards for Chronic Transfusion Therapy in Children with Sickle Cell Anemia and Stroke.
Authors: Ware Russell E. , McMurray Marsha A. , Schultz William H. , Alvarez Ofelia A. , Aygun Banu , Cavalier Mary Ellen , Files Bea , Daeschner Charles W. , Driscoll Catherine , Heeney Matthew M. , Hilliard Lee , Iyer Rathi V. , Kalinyak Karen , Kwiatkowski Janet , Lane Peter A. , Lee Margaret , Miller Scott T. , Minniti Caterina , Mueller Brigitta , Rogers Zora R. , Sarnaik Sharada A. , Scott J.P. , Thompson Alexis , Wang Winfred C. , Woods Gerald M. , Yang Yih-Ming , Helms Ronald S. 
Published: April 2020

Abstract
Children with sickle cell anemia have a 5–10% incidence of primary stroke, after which they have a 50–90% risk of stroke recurrence. Monthly transfusions with a goal of maintaining sickle hemoglobin (HbS) &lt;30% can lower the risk of secondary stroke to 10–20%. In practice, however, this 30% goal can be difficult to achieve, due to both physiological and practical considerations. The NHLBI-sponsored Phase III Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial will compare standard therapy (transfusions and chelation) to alternative therapy (hydroxyurea and phlebotomy) for the prevention of recurrent stroke and management of iron overload in children with sickle cell anemia and previous stroke. In SWiTCH, transfusions in the standard treatment arm will be given according to the current academic standard, rather than an arbitrary %HbS level. To determine the current academic community standards for secondary stroke prophylaxis in children with sickle cell anemia, 23 SWiTCH clinical sites reported data from children receiving monthly transfusions to prevent recurrent stroke. Transfusion-related data were collected for all SWiTCH-eligible patients over the 12-month period from 9-1-04 until 8-31-05, including age, weight, transfusion type and volume, and pre-transfusion hemoglobin concentration and %HbS. Data were analyzed both "per transfusion" and "per patient". A total of 3543 transfusions were administered to 295 pediatric patients over this 12-month period, with a median of 12 transfusions per patient. The average age (mean ± 1 SD) was 12.0 ± 3.8 years and the average weight was 39.7 ± 16.2 kg. The average volume of blood administered per transfusion was 14.2 ± 7.1 mL/kg with an annualized transfusion volume of 160 ± 78 mL/kg/year. Most children (56%) received primarily simple transfusions, 37% primarily exchange transfusions (20% manual partial, 17% automated), and 7% multiple transfusion types. Most children had good adherence to the transfusion program, with late transfusions (defined as &gt;7 days after the scheduled date) occurring once in 22% and twice or more in 12% of children. The average pre-transfusion Hb was 9.0 ± 0.7 gm/dL. The average pre-transfusion %HbS was 35 ± 11 %, with a median %HbS value of 34%. Potential "cutoff " %HbS values for SWiTCH included 34% (50th percentile of reported values), 43% (75th percentile), and 52% HbS (90th percentile). These data indicate that transfusions to prevent recurrent stroke vary among academic pediatric institutions and 30% HbS may not be a realistic goal for this study. Although the goal for transfusions in the SWiTCH standard treatment arm will remain 30% HbS, maintaining an average pre-transfusion HbS value of ≤ 45% will be required to reflect the academic community standard.