Correlation between leukocyte‐platelet aggregates and thrombosis in myeloproliferative neoplasms

Abstract

Introduction The impact of activated blood and endothelial cells on the thrombosis in myeloproliferative neoplasms (MPN) has not yet been clarified. We prospectively analyzed correlation between circulating leukocyte‐platelet aggregates and soluble selectins to thrombosis occurrence in MPN, in the context of standard and cardiovascular risk factors, and different clinical and biological characteristics. Methods Flow cytometric analysis of neutrophil‐platelet (Neu‐Plt) and monocyte‐platelet (Mo‐Plt) aggregates in peripheral blood, as well as quantification of soluble E‐/L‐/P‐selectins by enzyme immunoassay, was performed on 95 newly diagnosed MPN patients. Results During the follow‐up, thrombosis occurred in 12.6% MPN patients (arterial 9.4%, venous 3.2%), with a mean time of 39 months. The overall incidence rate of main thrombotic events was 4.36 per 100 patient‐years. The incidence of arterial hypertension (HTA) was significantly higher in patients with thrombosis, compared to those without thrombosis (P < .05). The level of soluble P‐selectin was significantly higher in patients with thrombosis compared to those without thrombosis (346.89 ng/mL vs 286.39 ng/mL, P = .034). The mean level of Neu‐Plt (26.7% vs 22.4%) and Mo‐Plt (17.8% vs 12.3%) aggregates did not differ significantly between the groups with and without thrombosis. A multivariate COX proportional hazard regression model confirmed an independent predictive significance of Mo‐Plt aggregates (HR = 1.561, 95% CI: 1.007‐2.420, P = .046), as well as the cumulative effect of Mo‐Plt aggregates and HTA (HR = 1.975, 95%CI: 1.215‐3.212, P = .006) for thrombosis occurrence. Conclusion Monocyte‐platelet aggregates represent an independent risk factor for thrombosis occurrence, further on supported by HTA.

Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation

“…Beyond paracrine mechanisms, platelets can also form aggregates with various leukocyte subtypes, such as neutrophils, monocytes, and T cells ( 11 , 14 , 15 ). Platelet-leukocyte aggregates have been suggested to drive vascular disease and may potentially represent a biomarker for thrombotic events ( 9 , 16 ).…”

Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity and Inflammation in Myeloproliferative Neoplasms

“…The copyright holder for this preprint this version posted December 11, 2022. ; https://doi.org/10.1101/2022.12.08.519689 doi: bioRxiv preprint hemostasis, platelets also contribute to thromboinflammatory processes by directly interacting with leukocytes 11 . Elevated platelet-leukocyte aggregates has recently been found to be an independent risk factor for thrombosis occurrence in MPN; it suggested that platelets may be a mediator between thrombosis and inflammation [12][13][14] . However, current evaluation of risk of MPNassociated thrombosis only consider quantitative change in platelets, the qualitative differences of platelets in MPNs have not been systematically evaluated.…”

Multiomic profiling reveals metabolic alterations mediating aberrant platelet activity and inflammation in myeloproliferative neoplasms

“…Aside from its classical functions in hemostasis, platelets also contribute to thromboinflammatory processes by directly interacting with leukocytes (11). Elevated platelet-leukocyte aggregates (PLAs) have recently been found to be an independent risk factor for MPN-associated thrombosis, indicating that platelets could be a mediator between thrombosis and inflammation (12)(13)(14). While it is known that thrombotic risk in MPNs is not directly correlated with the platelet count, the factors mediating aberrant activation of platelets in MPNs have not been systematically evaluated.…”