P118: THE ROLE OF HEMOGLOBIN AND HEMOLYSIS ON TRANSCRANIAL DOPPLER VELOCITIES IN CHILDREN WITH SICKLE CELL DISEASE: DATA FROM A NATURAL HISTORY COHORT
Authors: G Reggiani, B Coppadoro, V Munaretto, R Manara, C Baracchini, A Pieroni, F Viaro, I Agodoa, A Beaubrun, A Biffi, L Sainati, R Colombatti
Journal: HemaSphere (2022)

Background: Children with sickle cell disease (SCD) are at increased risk of cerebrovascular events that can impact neurocognitive development and quality of life (Colombatti 2016). Transcranial Doppler ultrasound (TCD) is a validated screening tool to identify pediatric SCD patients with the highest risk of stroke, to start on a preventive chronic blood transfusion regimen (Estcourt 2020; Inusa 2019). We aimed to evaluate the distribution of TCD velocities in a pediatric natural history cohort and investigate their correlation with hematological variables and treatments. Methods: We performed a retrospective analysis on data from a prospective pediatric cohort followed from January 1, 2009, to December 31, 2020 (censoring date). We used transcranial Doppler imaging (TCDi) and classified results according to STOP criteria, considering terminal internal carotid artery (TICA) and middle cerebral artery (MCA) time-averaged maximum mean velocities (TAMMVs). Hematological, clinical, and treatment variables were available from the natural history cohort database. Two-sample and Welch t-tests for unequal variances were used to compare mean hemoglobin (Hb) values and hemolysis markers in patients with and without abnormal/conditional TCDi results. Fisher and chi-square tests were used to compare categorical variables. Linear regression models were used to assess the effects of MCA and TICA TAMMVs as continuous variables on Hb. Odds ratios (ORs) for neurological events at different Hb levels were estimated using generalized estimated equations (GEE) with a binomial distribution, logistic function, and exchangeable correlation structure, allowing for correlation among repeated observations for the same patient. Multivariable GEE including characteristics and treatment variables were used to evaluate the association between neurological events and Hb. Results: Of the 182 SCD patients in the cohort, 169 had assessments of cerebral vasculopathy, and 155 had evaluable TCDi (583 exams). The median follow-up of the entire cohort was 79.8 months (range: 2.1–298.6 months) (interquartile range [IQR]: 36.9–126.3 months). The median age at the censoring date was 13.4 years (IQR: 9.1–17.5 years). Patients with abnormal/conditional TCDi results had lower Hb (8.4 vs 8.9 g/dL, P≤0.0001) and higher reticulocyte counts (317,766 vs 262,750/mm3, P≤0.0001), lactate dehydrogenase (843 vs 690 U/L, P=0.0012), and aspartate aminotransferase (61 vs 54 U/L, P=0.0007) compared with patients with normal/low results. We detected an inverse linear correlation between TICA/MCA TAMMVs and Hb (Figure 1A and 1B). Univariate analysis showed significant inverse correlation between abnormal/conditional TCDi results and Hb considered as a continuous variable (OR: 0.484, P<0.001). In the multivariate analysis, the correlation between TCDi results and Hb remained significant; moreover, the risk of presenting abnormal/conditional TCDi results decreased with age (OR: 0.833, P<0.0064). Conclusions: This analysis from our natural history cohort shows a significant inverse correlation between Hb and MCA and TICA velocities, supporting the beneficial effect of higher Hb levels in reducing TAMMV.References 1. Colombatti R, et al. PLoS One. 2016;11(6):e-157090. 2. Estcourt LJ, et al. Cochrane Database Syst Rev. 2020;4(4):CD012389. 3. Inusa BPD, et al. J Clin Med. 2019;9(1):44.