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

Abstract

(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.

Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy

“…Premature vascular aging in allo-HCT patients may have been expected based on evidence from small cross-sectional and prospective studies which have evaluated vascular structure and function in the allo-HCT setting. Indeed, allo-HCT recipients have been shown to exhibit increased endothelial damage and dysfunction (evidenced by elevated circulating endothelial cells and soluble markers of endothelial damage, and lower endothelial dependent flow-mediated dilation) ( 50 – 53 ), central arterial stiffening (evidenced by increased aortic pulse wave velocity and reduced carotid distensibility, compliance and incremental elastic modulus) ( 54 – 56 ), and carotid intima-media thickening ( 54 ) compared to age-matched healthy controls or pre-transplant values. Consequently, hypertension is a common early (1-month incidence: 38–61%) ( 57 , 58 ) and persistent complication of allo-HCT (odds ratio: 3.65 [95% CI, 1.82–7.32] at 8.6 years after allo-SCT) ( 59 ).…”

Bilateral optic neuropathy as a complication of allogeneic hematopoietic stem cell transplantation

“…Patients after allogeneic transplantation have a higher risk of thrombotic complications due to the vulnerability of the vascular endothelium 16 .…”

Von Willebrand Factor, Factor VIII, and Other Acute Phase Reactants as Biomarkers of Inflammation and Endothelial Dysfunction in Chronic Graft-Versus-Host Disease

“…This concept is further underpinned by their proven good prognostic value in chronic autoimmune diseases clinically resembling cGvHD. In addition to the aforementioned factors it may also be helpful to assess endothelium-derived microvesicles for endothelial injury and procoagulant activity (147). Still, the influence of patient-related parameters should definitely be taken into consideration, and for that reason further prospective studies addressing this issue and the precise role of endothelial injury in cGvHD in general are needed.…”