Sickle cell disease (SCD) patients experience chronic anemia and vaso-occlusion leading to a lack of oxygen delivery to tissues. The resulting complications, including stroke, silent cerebral infarction, and cognitive impairment, decrease quality of life and increase mortality in SCD. While elevated cerebral blood flow and oxygen extraction fraction (OEF) have been consistently reported in the pediatric and adolescent SCD population, the pulsatile characteristics associated with OEF and SCD are not well understood in adults. In this study, we aim to address this gap by measuring how cardiac pulsatility impacts regional oxygen supply-demand across different vascular beds in the cerebral and peripheral regions of adults with SCD.

We hypothesized that adults with SCD would exhibit altered cerebral and peripheral blood flow parameters compared to controls, reflecting vascular dysfunction related to chronic anemia, vaso-occlusion, and hemolysis. Thus, we employed Diffuse Correlation Spectroscopy (DCS) and near infrared spectroscopy (NIRS) to measure regional blood flow and oxygen saturation (arterial oxygen saturation (SpO₂), tissue saturation (StO₂), and OEF) in the cerebral cortex and forearm muscle. We enrolled 45 adults (controls: n=24; SCD: n=21), from whom we collected blood flow measurements, lab measurements and demographic information. From the DCS data, we extracted pulsatile features of the cardiac waveform, being peak systolic flow (PSF) and end diastolic flow (EDF), which reflect the maximum and minimum blood flow during cardiac cycle, the pulsatility index (PI), which quantifies the pulsatility of the blood flow in the vessels, and area under the curve (AUC) of cardiac pulses, which measures the overall of blood volume delivered in a cardiac cycle. Using a linear regression model, we also analyzed covariates of hematocrit (Hct) and presence of SCD.

Cerebral OEF was significantly higher (mean= 0.38) than controls (mean = 0.27, p < 0.001), which is in agreement with literature. We found a significant negative correlation between the cerebral OEF and Hct (r = -0.76, p < 0.01), which means physiologically with fewer red blood cells and hemoglobin molecules to carry oxygen, a greater percentage of oxygen is being extracted from the blood. We find that while the SCD population has lower Hct and Higher OEF (r = -0.51, p = 0.021) compared to the controls (r = -0.58, p = 0.031), the strength and direction of the correlations are similar between controls and SCD, suggesting a closely regulated relationship between Hct and OEF.

A weak, non-significant positive correlation was found between cerebral AUC and StO2 (r=0.154, p = 0.328). Cerebral AUC showed a weak positive correlation with Hct (r = 0.233, p = 0.178), suggesting decreased vascular reactivity at lower Hct. The forearm, on the other hand, exhibited a weak inverse correlation (ns) between AUC and Hct (r = -0.162, p = 0.383), which may show intact peripheral autoregulatory mechanisms that attenuate hemodynamic response to increased hematocrit in the blood.

We found that those with SCD exhibited a wider observed range (PSF: IQR Range = 1.15 to 1.4, EDF: IQR Range = 0.66 to 0.85 and PI: IQR: 0.3 to 0.7) and greater variability of blood flow parameters compared to controls (PSF: IQR = 1.19 to 1.31, EDF: IQR = 0.79 to 0.83 and PI: IQR : 0.38 to 0.52). Although these parameters were not statistically significant, they provide us with questions to study further to understand their physiological significance. In contrast, cerebral blood flow parameters in the SCD group were characterized by a narrower variability when compared to controls, which may suggest that cerebral autoregulation is functioning to maintain stable flow in the state of chronic anemia.

These findings address an important gap by offering a first potential mechanistic look at regional oxygen supply-demand dynamics across different vascular beds in adults with SCD. Pediatric studies reported elevated flow with increased OEF, but did not report how cardiac function is linked to tissue oxygenation. Our future direction is to enroll more participants to achieve better biomarkers for SCD studies.

This content is only available as a PDF.
2025
Sign in via your Institution