Abstract Number: LPB0038
Meeting: ISTH 2021 Congress
Background: Neutrophil recruitment to inflamed endothelium significantly contributes to the hypercoagulable state seen in sickle cell disease (SCD). We previously demonstrated that neutrophil binding on E-selectin was significantly enhanced under hypoxia in SCD. However, we observed considerable heterogeneity in adhesion profiles and clinical characteristics of SCD. Here, we interrogated if the differential interaction of neutrophils with E-selectin is mechanistically linked to clinical features and the course of SCD.
Aims: To investigate if profiles of differential neutrophil binding on E-selectin correlate with clinical characteristics of SCD.
Methods: Venous blood samples were collected from 35 adult patients with homozygous (HbSS) SCD in EDTA vacutainers during a non-crisis clinic visit. Samples were re-calcified with Hank’s buffer (1:1 v/v) and injected into E-selectin immobilized microchannels at typical shear stress values seen in post-capillary venules. Neutrophils bound on E-selectin under shear were quantified in a 32 cm2 window (Fig 1A-B).
Results: Two groups of patients with distinct lactate dehydrogenase (LDH) levels and absolute reticulocyte counts (ARCs) were identified based on K-means cluttering analysis (Fig. 1C). Group 2 patients (N = 19) had significantly higher LDH levels and ARCs as well as lower number of neutrophils bound on E-selectin (Fig. 1D) and fetal hemoglobin (HbF) levels (Fig. 1E) compared to Group 1 patients (N = 16). Moreover, 79% (15/19) of Group 2 patients were transfusion-dependent compared to 31% (5/16) of Group 1 patients. Mechanistically, the degree of neutrophil activation, assessed by L-selectin shedding/blockade, was inversely related to neutrophil binding on E-selectin (Fig. 1F-H).
Conclusions: Our results show that SCD patients with a more severe hemolytic phenotype and greater transfusion dependency have constitutively less neutrophil binding on E-selectin. Further, profiling neutrophil adhesion may help predict response to anti-E-selectin therapy. Future experiments will focus on analyzing neutrophil adhesion on ICAM-1 or endothelial cells for assessing αMβ2 upregulation levels.
To cite this abstract in AMA style:Man Y, Kucukal E, Liu S, An R, Goreke U, Wulftange WJ, Sekyonda Z, Cheng K, Bode A, Hill A, Monchamp K, Little JA, Manwani D, Stavrou EX, Gurkan UA. Neutrophil Binding on E-selectin: a Potential Biomarker of Clinical Course and Response to Therapy in Sickle Cell Disease [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/neutrophil-binding-on-e-selectin-a-potential-biomarker-of-clinical-course-and-response-to-therapy-in-sickle-cell-disease/. Accessed November 29, 2023.
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