Evaluation of STOP Protocol Implementation for Abnormal TCD in Children with Sickle Cell Anemia at Risk for Stroke: Displace Consortium
Authors: Phillips Shannon , Schlenz Alyssa M , Dooley Mary , Mueller Martina , Sirline Logan P , Melvin Cathy L , Adams Robert J , Kanter Julie 
Published: November 2020

Introduction: Without intervention, children with sickle cell anemia (SCA) have an 11% chance of overt ischemic stroke. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) proved that children with SCA at increased risk of stroke can be identified using transcranial Doppler ultrasound (TCD) and, for those at risk, chronic red cell transfusion (CRCT) therapy is effective at preventing stroke. The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines include annual TCD screening for children with SCA ages 2 - 16, and CRCT for primary and secondary ischemic stroke prevention. The NHLBI-funded Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) project was designed to 1.) evaluate current stroke screening and prevention practices in a 28-site consortium through intensive medical record review and an electronic data capture system, 2.) determine barriers and facilitators to stroke prevention practices through qualitative methods, and 3.) design and deliver interventions to increase rates of 'sickle stroke screening' using implementation strategies. The purpose of this abstract is to describe initial (pre-study) consortium actions following abnormal TCD results including whether all children had a repeat TCD within the next 4 weeks, whether they initiated CRCT, characteristics of which children received CRCT, and what alternate treatments were used.
Methods: DISPLACE data collection years were 2012 - 2016. 5247 children with SCA who met criteria for annual TCD screening were entered into the electronic data capture system with clinical and demographic information. 163 children with abnormal TCD results were identified from the cohort database. Additional data were collected and subsequently adjudicated including timing of follow-up testing (repeat TCD or MRI) after abnormal TCD, implementation of CRCT following abnormal TCD, alternate treatment following abnormal TCD, and whether the STOP protocol was implemented. Data were analyzed using descriptive statistics.
Results: In response to abnormal TCD, 75% of children had a repeat TCD ordered (Table 1). Of these, most repeat TCDs were completed within 3 months, with &lt;10% delayed (longer than 12 weeks). CRCT was initiated in 69% of children with abnormal TCD (Table 2); of these, 17% had delayed initiation of CRCT. After abnormal TCD, 10% of families declined CRCT though suggested by providers. When some of these children later suffered an ischemic stroke, (20%) started CRCT at that time. The TWiTCH protocol (CRCT transitioning to HU in children without severe vasculopathy) was followed in about 1/4 of children on CRCT. Additional treatments following abnormal TCD included initiation of HU (64%) and bone marrow transplant (4%) (Table 3). Characteristics of children on CRCT are described in Table 4. Notably, of the 19 children whose CRCT was delayed, 15 (79%) had a stroke. There were 48 instances in which the STOP protocol was not implemented following abnormal TCD. Half of these were the result of decisions at the parent level (e.g., the parent refused CRCT, parent requested HU instead of CRCT). Five were provider decisions (e.g., provider suggested HU), and 15 were systems-level issues (e.g., repeat TCD was delayed). One was a combination of parent decision and system-level issue, and in 4 cases, the reason was unknown.
Conclusions: In this nationally representative sample of children with SCA at risk for stroke, nearly ¾ of children had a repeat TCDs, suggesting confirmation of abnormal results was common prior to beginning CRCT. Notably, there were a large number of ischemic strokes in children when CRCT was delayed futher confirming the utility of the screening and stroke prevention protocol. An additional key concern identified in this study were the barriers to STOP protocol implementation. Common reasons for lack of implementation included the parent's decision for HU instead of CRCT, delays in CRCT initiation, and delays in obtaining repeat TCDs. Difficulties implementing the STOP protocol suggest the need for interventions for more rapid initiation of CRCT and stroke prevention.

Disclosures
Kanter: AGIOS: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Sanofi: Consultancy; bluebird bio, inc: Consultancy, Honoraria; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees.