114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Assessment and Prevention of End-Organ Injury in Sickle Cell Disease

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Stéphanie Forté, Olivia Sobczyk, Julien Poublanc, et al.

Authors Conclusion from the Abstract: All three measures of cerebrovascular health (CVR, amplitude, and tau) in SCD patients were abnormal compared to normal controls. Hematocrit appears to be the strongest independent predictor of these measures. The protocol we applied for measuring CVR provides a standardized reproducible vasodilatory stimulus, enabling comparison against a population of healthy individuals for a more accurate assessment of CVR in individual subjects. Furthermore, the stimulus protocol produces rapid changes in arterial CO2 levels within one breath that can be used to measure the speed of response of the vasculature representing a novel metric of vascular performance postulated to represent vessel compliance and functional endothelial integrity. These findings show that the CVR methodology represents a promising tool to assess disease state, stroke risk, and therapeutic efficacy in sickle cell patients and merits further investigation.

Francoise Bernaudin, Suzanne Verlhac, Cécile Arnaud, et al.

Authors Conclusion from the Abstract: This study reports eICA arteriopathy kinetics using a longitudinal cohort of SCD children systematically assessed by Doppler and cMRA. While we confirm that only SCA and not SC/Sb+ children are at risk of intra/extracranial arteriopathy, we show for the first time that extracranial arteriopathy progressively develops as early as 2 years old in SCA-children and reaches a plateau around 10 years of age, as for intracranial arteriopathy. Furthermore, eICA tortuosities, which are the risk factor for eICA arteriopathy, are themselves significantly and independently associated with the SCA genotype and the severity of hemolytic anemia.

Sossena Wood, Abeselom Fanta, Atinuke Dosunmu-Ogunbi, et al. 

Authors Conclusion from the Abstract: We provide preliminary evidence that FD-NIRS can be used to assess cerebral autoregulation in SCD. Our results confirm and extend those of a prior study by Reinhard et al, 2003, by using the phase latency, Arg(D)−Arg(O), and the amplitude ratios, |D|/|O|, to assess autoregulation. In addition, we detected a noticeable reduction in oxygen saturation in patients with SCD as compared to healthy controls. Further studies may extend our findings to additional frequencies in a larger sample size to more comprehensively assess the impact of mean arterial pressure on autoregulation. Noninvasive measurement of cerebral autoregulation and brain oxygenation in SCD by FD-NIRS may represent a novel biomarker of cerebral vasculopathy in SCD and may help monitor changes in cerebral oxygenation, particularly during treatment with drugs that modulate the hemoglobin oxygen affinity, such as the recently FDA-approved voxelotor.

Emily Limerick, Neal Jeffries, Clarissa Diamantidis, et al.

Authors Conclusion from the Abstract: This study demonstrates that HSCT in patients with SCD is not associated with a significant increase in CKD incidence or prevalence at 2 and 3 years post-HSCT. While there is a substantial decline in eGFR from baseline to each annual follow-up, the proportion of patients whose eGFR was in the normal range increased and the prevalence of hyperfiltration decreased. The stability of UACR after an initial increase at the 1-year time point further suggests that even more mild renal damage may stabilize after transplant. Finally, AKI occurred in over half of the patients in our cohort, though the preponderance developed mild AKI.

Solomon Johnson, Victor R. Gordeuk, Roberto Machado, et al.

Authors Conclusion from the Abstract: These findings support links between changes of vital signs during the 6MWT and established markers of hemolysis and cardiovascular dysfunction in SCD patients. Evidence of a protective effect of increased systolic pressure is a novel finding. This might indicate that the ability to increase systolic pressure during submaximal exercise relates to cardiac output and conveys a physiological advantage for SCD patients. These findings could be used as the basis for future mechanistic studies of exercise effects on cardiovascular function in SCD patients.