Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S

Abstract

Many subjects carrying inherited thrombophilic defects will never experience venous thromboembolism (VTE) while other individuals developed recurrent VTE with no known additional risk factors. High levels of circulating microparticles (MP) have been associated with increased risk of VTE in patients with factor V Leiden and prothrombin G20210A mutation, suggesting a possible contribution of MP in the hypercoagulability of mild genetic thrombophilia. The role of MP as additional risk factor of VTE in carriers of natural clotting inhibitors defects (severe thrombophilia) has never been assessed. Plasma levels of annexin V-MP, endothelial-derived MP (EMP), platelet-derived MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) were measured in 132 carriers of natural anticoagulant deficiencies (25 antithrombin, 63 protein C and 64 protein S defect) and in 132 age and gender-matched healthy controls. Carriers of natural anticoagulant deficiencies, overall and separately considered, presented with higher median levels of annexin V-MP, EMP, PMP, TF+MP and PPL activity than healthy controls (p< 0.001, < 0.001, < 0.01, 0.025 and 0.03, respectively). Symptomatic carriers with a previous episode of VTE had significantly higher median levels of annexin-V MP than those without VTE (p=0.027). Carriers with high levels of annexin V-MP, EMP and PMP had an adjusted OR for VTE of 3.36 (95% CI, 1.59 to 7.11), 9.26 (95% CI, 3.55 to 24.1) and 2.72 (95%CI, 1.16 to 6.38), respectively. Elevated levels of circulating MP can play a role in carriers of mild and severe inherited thrombophilia. The clinical implications of this association remain to be defined.

Activated Platelet‐Derived and Leukocyte‐Derived Circulating Microparticles and the Risk of Thrombosis in Heparin‐Induced Thrombocytopenia: A Role for PF4‐Bearing Microparticles?

“…Events smaller than 0.3 lm and also 50% of 0.3 lm events were eliminated from analysis given the difficulty to distinguish them from background noise ( Fig. MP concentration in plasma was calculated automatically by the instrument software using the assayed concentration according to the formula: events/lL 5 total number of MPs counted/total number of fluorospheres counted 3 flow-count fluorospheres assayed concentration, as previously described (33). Moreover, in order to separate actual events from background noise, we defined MPs as particles that were 0.3-1.0 lm in diameter, had positive staining for annexin V-FITC (Fig.…”

“…Procoagulant activity of the MP was measured using the STAV R Procoag phospholipid (PPL) assay (Diagnostica Stago, Asnieres, France), as previously described (33,35). The PPL activity linearly correlates with the functional activity of MP present in the sample (36).…”

Elevated plasma levels of P‐selectin glycoprotein ligand‐1‐positive microvesicles in patients with unprovoked venous thromboembolism

“…Accordingly, we found that the risk of unprovoked VTE increased with 1.6‐fold per one standard deviation increase in plasma concentration of Annexin V + MVs. In addition, several studies have reported joint effects of plasma concentrations of Annexin V + MVs and inherited thrombophilias . The latter findings may suggest that elevated levels of circulating MVs can play a role in thrombus formation in subjects with mild and severe inherited thrombophilia.…”

Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives

“…The levels of circulating tissue factor bearing MP (TF + MPs) [84] or phosphatidylserine (PS + ) and lactadherin + MPs [85] are higher in patients with a hypercoagulable status than in control subjects. Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with pancreaticobiliary cancers (PBCs) [86].…”