**1.1 Definition of a microparticle**

Microparticles are submicron (<1.0µm) membrane bound circulating vesicles. Although anucleate, usually express cell surface antigen specific to the cell of origin, they may contain DNA or RNA and be virtually derived from any cell (Freyssinet 2003). The ISTH (International Society of Thrombosis and Haemostasis) vascular biology subcommittee defined these particles as being between 0.1-1.0 µm (SSCMembers Aug 2005). However, several other nanoscale techniques have demonstrated that particles <0.1 µm may also need to be considered as MP (Yuana*, et al*). Indeed, size range of MP is contentious with larger MP likely overlapping with small platelets and the smallest MP with exosomes (Gyorgy*, et al*, Jy*, et al*, Lawrie*, et al* 2009). Several factors may cause the production of MP from cells such as activation, complement mediated lysis, shearing stress, oxidative injury and active vesiculation (Horstman*, et al* 2004). The MP bear at least some surface characteristics of the parent cell and they differ from exosomes (0.03-0.1µm), which originate through the exocytosis of endocytic multivesicular bodies and play a role in antigen presentation (Freyssinet and Dignat-George 2005, Horstman*, et al* 2004, Horstman*, et al* 2007).

Microparticles: Role in Haemostasis and Venous Thromboembolism 5

leads to activation of a cascade of enzymes, which forms a fibrin clot. Microparticles of different cell origin could play a role in fibrin clot formation, enhance platelet leukocyte interactions and influence other plasma proteins such as von Willebrand's factor. Given that platelet MP constitute the majority of the circulating MP, they are considered an important effector of the haemostatic process (Morel*, et al* 2006). Some MP have also been described to carry molecules with anticoagulant function on their surface (Freyssinet 2003). The balance of pro and anticoagulant bearing MP in the endovascular milieu is likely to influence the

propensity to bleed or clot in a particular patient.

*et al* 2007, Morel*, et al* 2006).

**2.3.1 Platelet MP and coagulation** 

MP in haemostasis is illustrated in figure 1.

pathologic conditions.

**2.3 Platelet MP** 

**Type of MP Example of surface marker on MP** 

Anti-coagulant Tissue Factor Pathway inhibitor

Tissue Factor

Protein C/S Thrombomodulin

Platelet Factor 3 activity

Table 2. The possible pro and anticoagulant markers on the surface of microparticles (Enjeti*,* 

Traditionally, platelets major function was thought to be due to their aggregability and ability to plug damaged endothelium and capillary vessels. More recently, they are thought to form an important substrate for the coagulation pathway with their membrane providing the surface for the formation of the prothrombinase complex (comprising the Xa and Va complex). This enzyme complex leads to conversion of fibrinogen to fibrin which in combination with a variety of other factors leads to a stable clot at the site of injury. The presence of platelet microparticles at the site of blood vessel injury may contribute to this process by providing a large source of surface membrane for assembly of the enzymatic process. Indeed the exposure of phosphotidylserine at the site of thrombin generation increases the enzymatic catalyic effect by several hundred fold (Aleman). Platelets thus appear to have two major physiological roles for achieving haemostasis - form a platelet plug at the site of endothelial injury and generate microparticles which provide a surface for activation of the coagulation cascade leading to formation of the fibrin clot. The third possible role for the platelet MP could possibly be in maintaining the integrity of normal resting endothelium (Cambien, 2004). This area is still being actively explored. The role of

Apart from procoagulant function MP could also be involved in anticoagulant activity. Microparticles with TFPI (tissue factor pathway inhibitor) and antithrombin activity have been described (Morel*, et al* 2006, Siljander). However, the anticoagulant MP have not been as extensively studied and it would be interesting to evaluate these MP - its association with

Procoagulant von Willebrand's Factor


Table 1. Microparticle source, surface antigen expression and proportion in circulation (Enjeti*, et al* 2007, Siljander).
