{"doi":"10.1002/ajh.25954","title":"Reduction in <scp>transcranial doppler ultrasound (TCD)</scp> velocity after regular blood transfusion therapy is associated with a change in hemoglobin S fraction in sickle cell anemia","abstract":"Abnormal transcranial doppler ultrasound (TCD) velocity is a risk factor for stroke in children with sickle cell anemia (SCA). The STOP trial demonstrated that transfusions reduce TCD velocity and stroke risk.1 However, neither STOP1 nor STOP II2 results reported the unit decline in hemoglobin S (HbS) fraction per unit change in TCD velocity. In a pooled analysis of 10 studies demonstrating the relationship between hydroxyurea and TCD measurements, the average drop in TCD velocity was 21 cm/s (95% confidence interval [CI], 14.8-29.0)3 after hydroxyurea therapy. The pooled analysis did not demonstrate any change in the HbS fraction per unit change in TCD velocity. However, Hurlet-Jensen and colleagues demonstrated that a decline in HbS fraction has a more significant impact on cerebral blood flow (ie, rate of blood delivery to tissue; mL/100 g/min) than an increase in the total hemoglobin level.4 Here, we tested the hypothesis that HbS fraction has a more significant impact on the TCD velocity than total hemoglobin in individuals with SCA. The SIT trial participants included children aged 5-15 years at the time of enrollment, with a confirmed diagnosis of hemoglobin SS or hemoglobin Sβ0 thalassemia; time-averaged maximum mean TCD velocity of the terminal portion of the internal carotid or the proximal portion of the middle cerebral artery <200 cm/s by non-imaging technique, or time-averaged maximum velocity <185 cm/s by imaging technique; and no prior history of overt strokes or seizures. Inclusion criteria for this secondary analysis: (a) SIT trial participant randomized to regular transfusions; (b) completed at least 10 transfusions; (c) at least two TCD exams completed, with the first TCD before the start of regular blood transfusion; (d) and the second TCD performed near to the time of transfusions; and (e) HbS at baseline and at the time of follow-up TCD. Exclusion criterion: any neurological event during the SIT trial. The trial was approved by the Institutional Review Boards (IRB) at all participating institutions and registered at https://clinicaltrials.gov/ (NCT00072761). Informed consents were performed per local IRB procedures. Participant characteristics were described by median and interquartile range (IQR) for continuous measures and by number and percent for categorical measures. Multivariable mixed regression models of longitudinal change in TCD were constructed, with age and time as covariates, and separate models for hemoglobin S or total hemoglobin because of sample size. Based on the evidence that decreasing HbS fraction and increasing hemoglobin levels are associated with a decrease in TCD velocities,5 a two-sided P value ≤.05 was considered statistically significant. Data analysis was performed using SPSS, version 26.0 (IBM, Armonk, New York). From the randomized SIT cohort of 99 children who received approximately monthly blood transfusions, 50 completed at least 10 transfusions and had at least two TCD evaluations. Of these 50, 24 had paired TCD measurements, with one excluded for a neurological event and one excluded for missing HbS value, thus 22 had the first TCD measurement before transfusion (median 2.2 months, IQR 0.8-3.7), and the second TCD measurement completed within a median −0.1 month (IQR −0.6 to 0.1 months) of the last transfusion. The median HbS fraction of 20.5% at the time of the second TCD measurement provides evidence that the participants had reached a steady-state of regular blood transfusion therapy when the goal was to keep the maximum HbS percentage less than 30%. The median interval between the first and the last TCD was 2.5 years. After initiating transfusion therapy, TCD assessment was not performed as part of the trial protocol because the TCD measurement after initiating transfusion has not been associated with a future incidence rate of ischemic strokes.6 All 22 children had HbS fractions available at the time of TCD examinations, and later when receiving regular blood trans","journal":"American Journal of Hematology","year":2020,"id":112467,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353139,"name":"Mark Rodeghier","orcid":"0000-0001-7258-0073","position":1,"is_corresponding":false},{"id":326159,"name":"Manus J. Donahue","orcid":"0000-0002-4123-9275","position":2,"is_corresponding":false},{"id":24956,"name":"Michael R. DeBaun","orcid":"0000-0002-0574-1604","position":3,"is_corresponding":false},{"id":292916,"name":"Lori C. Jordan","orcid":"0000-0001-7240-0415","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-18T23:13:13.874980Z","pmid":"32777083","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}