Markers of endothelial cell activation and neutrophil extracellular traps are elevated in immune thrombocytopenia but are not enhanced by thrombopoietin receptor agonists.

Autor: Garabet L; Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Norway; Department of Research, Østfold Hospital Trust, Norway; Institute of Clinical Medicine, University of Oslo, Norway. Electronic address: lamyagarabet@hotmail.com., Henriksson CE; Institute of Clinical Medicine, University of Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Norway., Lozano ML; Hospital JM Morales Meseguer, Centro Regional de Hemodonacion, IMIB-Arrixaca, Murcia, Spain; Grupo de investigación CB15/00055 del Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain., Ghanima W; Department of Research, Østfold Hospital Trust, Norway; Institute of Clinical Medicine, University of Oslo, Norway., Bussel J; New York Presbyterian Hospital, Weill Cornell, United States., Brodin E; Department of Haematology, Akershus University Hospital, Norway., Fernández-Pérez MP; Hospital JM Morales Meseguer, Centro Regional de Hemodonacion, IMIB-Arrixaca, Murcia, Spain., Martínez C; Hospital JM Morales Meseguer, Centro Regional de Hemodonacion, IMIB-Arrixaca, Murcia, Spain., González-Conejero R; Hospital JM Morales Meseguer, Centro Regional de Hemodonacion, IMIB-Arrixaca, Murcia, Spain., Mowinckel MC; Research Institute of Internal Medicine, Oslo University Hospital, Norway; Department of Haematology, Oslo University Hospital, Norway., Sandset PM; Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Norway; Department of Haematology, Oslo University Hospital, Norway.
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2020 Jan; Vol. 185, pp. 119-124. Date of Electronic Publication: 2019 Nov 30.
DOI: 10.1016/j.thromres.2019.11.031
Abstrakt: Introduction: Patients with immune thrombocytopenia (ITP) are at increased risk of thrombosis, which seems to be further enhanced by treatment with thrombopoietin-receptor-agonists (TPO-RAs). The underlying mechanisms of thrombosis in ITP are not fully understood. Endothelial cell activation and neutrophil extracellular traps (NETs) play important roles in thrombosis, however, their roles in ITP itself, or in TPO-RA-treatment, have not yet been fully explored. We aimed to investigate whether endothelial cell activation and NETs are involved in the hypercoagulable state of ITP, and whether TPO-RA-treatment enhances endothelial cell activation and NET formation.
Material and Methods: We measured markers of endothelial cell activation including intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and thrombomodulin in 21 ITP patients, and E-selectin in 18 ITP patients. Markers of NET formation, citrullinated histone H3-DNA (H3Cit-DNA) and cell-free DNA (cfDNA), were measured in 15 ITP patients. All markers were measured before, and 2 and 6 weeks after initiation of TPO-RA-treatment in ITP patients, and in matched controls.
Results: Higher levels of ICAM-1, thrombomodulin, and H3Cit-DNA were found in ITP patients, both before and after TPO-RA-treatment, compared with controls. No differences were found for VCAM-1, E-selectin or cfDNA. TPO-RA-treatment did not further increase markers of endothelial cell activation or NET formation.
Conclusions: This study showed that ITP patients have increased endothelial cell activation and NET formation, both of which may contribute to the intrinsic hypercoagulable state of ITP. TPO-RA-treatment, however, did not further increase endothelial cell activation or NET formation indicating that other drug-associated prothrombotic mechanisms are involved.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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