**2.4 Tissue factor bearing MP**

Pathophysiology and Clinical Aspects of 6 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

Fig. 1. The interaction of MP of platelet and monocyte origin being recruited in thrombus

Platelet aggregation Collagen in adventitia

Tissue factor exposed at

site of endothelial injury and haemostasis

fibrin polymerization

Microparticle recruitment

Endothelial disruption

Platelet MP also bear a number of antigens such GPIIbIIIa, GPIa, von Willebrand's factor and arachidonic acid which may all be important effectors in the clotting mechanism. The understanding of the molecular mechanisms of haemostasis has now led to the thinking that coagulation can be described as an interaction between p-selection, tissue factor thrombin and microparticles (Furie and Furie 2004). P-selectin is an adhesion molecule expressed at the platelet endothelial interface which is thought to be critical for tissue factor activity and leukocyte adhesion in the thrombus (Myers, 2003). Some authors have even described Pselectin on microparticles, tissue factor and clotting proteins as being the molecular triad for

Another potential role of MP may be in the interaction of endothelium, von Willebrand's factor and platelets.The platelet derived microparticles could interact with the protease ADAMTS-13 (**A D**isintegrin **A**nd **M**etalloproteinase with **T**hrombo**S**pondin-1-like motifs, member **13** of this family of metalloprotease) , which regulates the activity of high molecular weight von Willebrand's factor. Increased microparticles in circulation could potentially compete in binding ADAMTS-13, reducing its interaction with the endothelium and influencing multimer cleavage (Jy*, et al* 2005). This may then contribute to the increased rates of thrombosis observed in these patients with thrombotic thrombocytopaenic purpura

formation at site of endothelial injury.

Monocyte interaction

Endothelial cell

circulating platelet

coagulation (Polgar, 2005).

**2.3.2 Molecular interactions of Platelet MP** 

though the evidence for this process is very preliminary.

In an intact blood vessel tissue factor is usually restricted to adventitia and protected by the endothelial layer. However, small amounts of monocyte related tissue factor have been isolated in circulation (Key). The presence of tissue factor (TF) bearing microparticles, mainly derived from monocytes, in circulation has been shown to participate in initiation of fibrin polymerization (Eilertsen and Osterud 2004, Key). Although usually found to be in very small numbers in normal circulation, these increase dramatically at the site of injury. The interaction between tissue factor bearing MP and platelet MP is also of interest as there appears to be some evidence that they may be complementary in terms of thrombin generation potential (Key and Kwaan).
