Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner

Abstract

Summary. Background: Circulating microparticles of various cell types are present in healthy individuals and, in varying numbers and antigenic composition, in various disease states. To what extent these microparticles contribute to coagulation in vivo is unknown. Objectives: To examine the in vivo thrombogenicity of human microparticles. Methods: Microparticles were isolated from pericardial blood of cardiac surgery patients and venous blood of healthy individuals. Their numbers, cellular source, and tissue factor (TF) exposure were determined using¯ow cytometry. Their in vitro procoagulant properties were studied in a ®brin generation test, and their in vivo thrombogenicity in a rat model. Results: The total number of microparticles did not differ between pericardial samples and samples from healthy individuals (P 0.786). In both groups, microparticles from platelets, erythrocytes, and granulocytes exposed TF. Microparticle-exposed TF antigen levels were higher in pericardial compared with healthy individual samples (P 0.036). Pericardial microparticles were strongly procoagulant in vitro and highly thrombogenic in a venous stasis thrombosis model in rats, whereas microparticles from healthy individuals were not [thrombus weights 24.8 (12.2±41.3) mg vs. 0 (0±24.3) mg median and range; P < 0.001]. Preincubation of pericardial microparticles with an inhibitory antibody against human TF abolished their thrombogenicity [0 (0±4.4) mg; P < 0.01], while a control antibody had no effect [19.6 (12.6±53.7) mg; P > 0.05]. The thrombogenicity of the microparticles correlated strongly with their TF exposure (r 0.9524, P 0.001). Conclusions: Human cell-derived microparticles promote thrombus formation in vivo in a TF-dependent manner. They might be the direct cause of an increased thromboembolic tendency in various patient groups.

Circulating Microparticles

“…48 This property may not be restricted to leukocyte-derived MPs, because the presence of tissue factor on platelet-erythrocyte-and hematopoietic cellderived MPs leads also to thrombus propagation in vivo. 49,50 In addition, similar observations were reported in vitro regarding endothelial MP-induced tissue factor expression and procoagulant activity in the monocyte cell line THP1. 51 In vivo, MPs are captured by thrombus-associated platelets through the interaction of MP P-selectin glycoprotein ligand (PSGL)-1 with platelet P-selectin, leading to a concentration of tissue factor, which initiates and accelerates blood coagulation and fibrin formation.…”

Thioredoxin and Thioredoxin Reductase Control Tissue Factor Activity by Thiol Redox-dependent Mechanism

“…Serum hTrx1 levels of coronary artery disease patients are negatively associated with disease severity (17). Because TF plays a critical role in thrombus formation in vivo (59), and enrichment of circulating TF in human atherosclerotic plaques is linked to plaque disruption (53), proper suppression of TF activity by hTrx1 or Trx system should have a favorable effect on human health.…”

Air pollution‐associated procoagulant changes: the role of circulating microvesicles

“…In healthy individuals, microvesicles derived from blood platelets and red blood cells account for almost all circulating microvesicles. As WBC-derived microvesicles are extremely low [50], we could not quantify these microvesicles via flow cytometry.…”