Chronic transfusion therapy improves but does not normalize systemic and pulmonary vasculopathy in sickle cell disease
Year: 2015
Type: article
Study design: Observational Study
Abstract: Tricuspid regurgitant (TR) jet velocity and its relationship to pulmonary hypertension has been controversial in sickle cell disease (SCD). Plasma free hemoglobin is elevated in SCD patients and acutely impairs systemic vascular reactivity. We postulated that plasma free hemoglobin would be negatively associated with both systemic and pulmonary endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery and TR jet velocity, respectively. Whole blood viscosity, plasma free hemoglobin, TR jet, and FMD were measured in chronically transfused SCD pre- and posttransfusion (N = 25), in nontransfused SCD (N = 26), and in ethnicity-matched control subjects (N = 10). We found increased TR jet velocity and decreased FMD in nontransfused SCD patients compared with the other 2 groups. TR jet velocity was inversely correlated with FMD. There was a striking nonlinear relationship between plasma free hemoglobin and both TR jet velocity and FMD. A single transfusion in the chronically transfused cohort improved FMD. In our patient sample, TR jet velocity and FMD were most strongly associated with plasma free hemoglobin and transfusion status (transfusions being protective), and thus consistent with the hypothesis that intravascular hemolysis and increased endogenous erythropoiesis damage vascular endothelia.
Source: Blood
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Children's Hospital Los Angeles, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1999843896, G2098862387, Erythrocyte Nitric Oxide Links Rheology and Vasculopathy in Sickle Cell Disease, G4758887890, Multimodal biophysical markers of vascular disease in hemoglobinopathies, G5399073165, General Clinical Research Center, G5919997565, Childrens Hospital Los Angeles Child Health Research Development Award, Iron-mediated vascular disease in sickle cell disease., G7537374094, G8444074154, Basic and Translational Research Program
OpenAlex ID: W1192008708