Assessment of Endothelial Injury and Pro-Coagulant Activity Using Circulating Microvesicles in Survivors of Allogeneic Hematopoietic Cell Transplantation

• Published in: International journal of molecular sciences 2020-12, Vol.21 (24), p.9768
• Main Authors: Gavriilaki, Eleni, Sakellari, Ioanna, Anyfanti, Panagiota, Batsis, Ioannis, Vardi, Anna, Bousiou, Zoi, Lazaridis, Antonios, Nikolaidou, Barbara, Zarifis, Ippokratis, Masmanidou, Marianna, Yiannaki, Efthalia, Markala, Dimitra, Anagnostopoulos, Achilles, Douma, Stella, Gkaliagkousi, Eugenia
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Blood Coagulation Factors; Cancer Survivors - statistics & numerical data; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - etiology; Case-Control Studies; Cell-Derived Microparticles - pathology; Endothelium, Vascular - injuries; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - pathology; Heart Disease Risk Factors; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Male; Middle Aged; Transplantation, Homologous; Young Adult
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms21249768

(1) Background: survivors of allogeneic hematopoietic cell transplantation (alloHCT) suffer from morbidity and mortality due to cardiovascular events. We hypothesized that vascular injury and pro-coagulant activity are evident in alloHCT survivors without existing alloHCT complications or relapse. (2) Methods: we enrolled consecutive adult alloHCT survivors without established cardiovascular disease and control individuals matched for traditional cardiovascular risk factors (January-December 2019). Circulating microvesicles (MVs) of different cellular origins (platelet, erythrocyte, and endothelial) were measured by a standardized flow cytometry protocol as novel markers of vascular injury and pro-coagulant activity. (3) Results: we recruited 45 survivors after a median of 2.3 (range 1.1-13.2) years from alloHCT, and 45 controls. The majority of patients suffered from acute (44%) and/or chronic (66%) graft-versus-host disease (GVHD). Although the two groups were matched for traditional cardiovascular risk factors, alloHCT survivors showed significantly increased platelet and erythrocyte MVs compared to controls. Within alloHCT survivors, erythrocyte MVs were significantly increased in patients with a previous history of thrombotic microangiopathy. Interestingly, endothelial MVs were significantly increased only in alloHCT recipients of a myeloablative conditioning. Furthermore, MVs of different origins showed a positive association with each other. (4) Conclusions: endothelial dysfunction and increased thrombotic risk are evident in alloHCT recipients long after alloHCT, independently of traditional cardiovascular risk factors. An apparent synergism of these pathophysiological processes may be strongly involved in the subsequent establishment of cardiovascular disease.