Microparticle analysis in disorders of hemostasis and thrombosis

Abstract

Microparticles (MPs) are submicron vesicles released from the plasma membrane of eukaryotic cells in response to activation or apoptosis. MPs are known to be involved in numerous biologic processes, including inflammation, the immune response, cancer metastasis, and angiogenesis. Their earliest recognized and most widely accepted role, however, is the ability to promote and support the process of blood coagulation. Consequently, there is ongoing interest in studying MPs in disorders of hemostasis and thrombosis. Both phosphatidylserine (PS) exposure and the presence of tissue factor (TF) in the MP membrane may account for their procoagulant properties, and elevated numbers of MPs in plasma have been reported in numerous prothrombotic conditions. To date, however, there are few data on true causality linking MPs to the genesis of thrombosis. A variety of methodologies have been employed to characterize and quantify MPs, although detection is challenging due to their submicron size. Flow cytometry (FCM) remains the most frequently utilized strategy for MP detection; however, it is associated with significant technological limitations. Additionally, pre-analytical and analytical variables can influence the detection of MPs by FCM, rendering data interpretation difficult. Lack of methodologic standardization in MP analysis by FCM confounds the issue further, although efforts are currently underway to address this limitation. Moving forward, it will be important to address these technical challenges as a scientific community if we are to better understand the role that MPs play in disorders of hemostasis and thrombosis.

Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?

“…It is interesting to note that the density of active TF on microvesicles is higher than that on their parental cells [30], which supports the hypothesis that MP formation is not an entirely random process and that MPs are effective products made in response to a changing environment. More recent data showed that MPs not only propagate coagulation by exposing PS but also initiate thrombin generation independently of TF and the extrinsic pathway [24]. These findings shed new light on the procoagulant properties of MPs and their possible hypercoagulable impact.…”

“…Different methods and combinations of methods have been developed to detect and analyze MPs [16,20,24,25,31,32]. Appropriate sampling conditions, processing, and sample storage are essential [33].…”

“…While there have been consistent reports of an association between elevated MPs levels and prothrombotic conditions [24,25,43], data on a direct causal relationship between circulating MPs levels and thrombotic events are inconclusive so far [44]. From a clinical standpoint, MPs as biomarkers for thrombotic risk could be helpful (i) in the acute VTE setting to help secondary prevention [45][46][47][48][49], and (ii) as prognostic biomarker of VTE for primary prevention.…”

“…MPs circulate in blood under physiological conditions and are detected and characterized based on their phospholipids and antigens compositions, which reflect their cellular origins. A wide spectrum of pathologies have been associated with increased MPs levels, namely coagulative disorders, inflammatory states, and vascular dysfunction [19,[21][22][23][24][25][26]. Most of these conditions are characterized by a hypercoagulable state, which may lead to venous thrombosis.…”

“…Most of these conditions are characterized by a hypercoagulable state, which may lead to venous thrombosis. Indeed, the direct link between MPs and VTE is supported by a considerable amount of new evidence [24,25,27]. MPs may become in the future one of the novel biomarkers for early primary and/or secondary VTE prevention protocols [28].…”