Clinical significance of procoagulant microparticles

Abstract

Microparticles (MPs) are small membrane vesicles that are released from many different cell types by exocytic budding of the plasma membrane in response to cellular activation or apoptosis. MPs may also be involved in clinical diseases because they express phospholipids, which function as procoagulants. Although flow cytometry is the most widely used method for studying MPs, some novel assays, such as tissue factor-dependent procoagulant assay or the ELISA method, have been reported. However, the use of quantification of MP as a clinical tool is still controversial. Elevated platelet-derived MP, endothelial cell-derived MP, and monocyte-derived MP concentrations are documented in almost all thrombotic diseases occurring in venous and arterial beds. However, the significance of MPs in various clinical conditions remains controversial. An example of this controversy is that it is unknown if MPs found in peripheral blood vessels cause thrombosis or whether they are the result of thrombosis. Numerous studies have shown that not only the quantity, but also the cellular origin and composition of circulating MPs, are dependent on the type of disease, the disease state, and medical treatment. Additionally, many different functions have been attributed to MPs. Therefore, the number and type of clinical disorders associated with elevated MPs are currently increasing. However, MPs were initially thought to be small particles with procoagulant activity. Taken together, our review suggests that MPs may be a useful biomarker to identify thrombosis.

Keywords: Flow cytometry; Microparticle; Phospholipid; Procoagulant activity; Thrombosis.

Figure 1

Mechanisms participating in the regulation of transmembrane migration of phosphatidylserine (PS) in activated platelets, followed by PDMP shedding. Phospholipid asymmetry is under the control of active flippase, while floppase and scramblase remain inactive. Following cellular activation, calcium is released from the endoplasmic reticulum, which can lead to the loss of phospholipid asymmetry and activation of calpain. PC, phosphatidylcholine; SM, sphingomyeline; PEa, phosphatidylethanolamine.

Figure 2

Different types of secreted membrane microparticles. Microparticles or pre-microparticles originally exist in multivesicular bodies. Following cellular activation, multivesicular bodies move close to the cellular membrane. Microparticles that are generated in multivesicular bodies are called exosomes once they are secreted. Secreted vesicles can form inside internal compartments from where they are subsequently secreted by fusion of these compartments with the plasma membrane. This microparticle is called an ectosome. Active calpain cleaves the cytoskeleton, leading to the formation of a membrane bleb and ectosome release. Exosome functionates by delivery system of some cellular substances. Ectosome possesses a procoagulant activity.

Figure 3

Role of MPs in type 2 diabetes into atherosclerosis and thrombosis. Production of PDMPs, MDMPs, and EDMPs can be increased in type 2 diabetes. These MPs contribute to the generation of atherothrombosis in type 2 diabetes. Mac-1: β-2 integrin family in monocyte (CD11b/CD18), ICAM-1: intercellular adhesion molecule-1, VCAM-1: vascular cell adhesion molecule-1.

Figure 4

Role of TF on MPs in activation of target cells. MPs can carry some substances, such as integrin, cell adhesion molecule, chemokines, phospholipids, and TF. TF mainly contributes to activation of the extrinsic coagulation system. PS, phosphatidylserine; CAM, cell adhesion molecule.