Changes of Platelet and Endothelial Microparticles in Patients with Venous Thromboembolism

Abstract

Background: Microparticles (MP) are small membrane vesicles released from a variety of cells including platelet, leukocyte, endothelial cell which mediate intravascular coagulation. In this study, the plasma levels of total microparticle (TMP), platelet microparticle (PMP) and endothelial microparticle (EMP) in patients with venous thromboembolism (VTE) were investigated to test their clinical utilities.Methods: Subjects were divided to 3 groups consisted of 119 patients with VTE, 72 cancer without VTE and 93 healthy controls. MP were assayed by flow-cytometry using non-washed, frozen platelet-poor plasma samples. TMP, PMP and EMP were identified using antibodies against Annexin V, CD41a, and CD144 respectively.Results: The mean levels of plasma TMP, PMP, but not EMP in VTE without caner group (n=77) were significantly increased compared with those in healthy controls (n=93); 1972.9/μl vs 917.0/μl, p=0.001; 1496.6/μl, 586.5/μl, p=0.001; 108.0/μl vs 97.8/μl, p=0.321). In the VTE without cancer group, the mean levels of plasma TMP, PMP, but not EMP in newly diagnosed VTE group (n=59) were significantly increased compared with previously diagnosed VTE group (n=18); 2242.5/μl vs 1089.1/μl, p=0.008; 1728.6/μl vs 735.9/μl, p=0.005; 101.8/μl vs 84.6/μl, p=0.885). Mean peak thrombin generations in VTE samples (n=9) were increased in platelet poor plasma (385.2 nM vs 163.1 nM, p=0.002) but not in microparticle free plasma (MFP) (86.2 nM vs 22.6 nM, p=NS) as compared with those of controls (n=10) suggesting the thombin generation is originated from MP of plasma. But, the mean levels of plasma TMP, PMP, but not EMP in VTE with caner group (n=42) were not increased compared with those in cancer controls without VTE (n=72); 2158.1/μl vs 1644.2/μl, p=0.094; 1637.2/μl vs 1246.8/μl, p=0.168; 86.0/μl vs86.0/μl, p=0.996). The plasma levels of B-TG were well correlated with those of PMP. The levels of plasma TMP, PMP, and EMP did not show any correlation with the level of D-dimer.Conclusion: The plasma levels of TMP and PMP are significantly increased in VTE patients and the levels are normalized after anticoagulation, suggesting MP may be used as surrogate markers for monitoring of VTE.