**3.1.2 Immune related VTE**

Pathophysiology and Clinical Aspects of 8 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

phosphatidylserine, on surface of stimulated platelets or derived microparticles, is critical for the formation of enzyme complexes in the clotting process (Zwaal*, et al* 2004, Zwaal*, et al* 2005). Mutations involving the ABCA1 ATP transporter have been reported in this

There are several other mechanisms by which MP influence the endovascular system. They may modulate endothelial function and carry proangiogeneic molecules (Lozito and Tuan). Recently MP bearing Sonic hedgehog have been shown modulate angiogenesis (Soleti*, et al* 2009, Soleti and Martinez 2009). They may also serve as novel carriers for transport of genetic material – such as mRNA or microRNA and these are currently areas of intense

From their role in physiology of haemostasis it can be extrapolated that excess production of MP will lead to a pathological state. Indeed, increase in circulating MP have been described in a wide variety of states. The role of MP in various thrombotic states is discussed below.

Venous thromboembolism is the result of a complex interaction between the circulating proteins, cells/platelets and the endothelium (Collen and Hoylaerts 2005). There is no known provoking or identifiable precipitating factor in idiopathic VTE. A recent study looked at the interactions between the MP of various origin - platelet, endothelial and monocyte and endothelial derived MPs were found to be elevated in association with VTE. One report suggests that the combination of total circulating MP, P-selectin levels and Ddimer levels may help predict VTE (Rectenwald*, et al* 2005). This approach had a sensitivity

In another larger investigation no association was found between levels of total circulating MP and risk of recurrent VTE (Ay*, et al* 2009). Interestingly, a study comparing patients with cancer who had VTE and those with idiopathic VTE found raised tissue factor bearing MP only in cancer patients (Thaler*, et al*). In another report, plasma levels of tissue factor MP were not raised in those with pulmonary embolism suggesting that that perhaps other subtypes of MP may have to be studied in more detail to explain the relationship found in experimental models (Garcia Rodriguez*, et al* 2010). Owen and co authors looked at the recurrence of VTE and found that the procoagulant activity but not number of MP was

The role of MP in predicting thrombosis in those with heritable thrombophilia has also been explored. It has been found that total circulating MP levels were increased in subjects with heterozygote factor V Leiden status but there was no difference between those who had had VTE and those without (Enjeti*, et al* 2010). This finding and other studies seems to suggest that although total microparticles have been shown to be increased in those with VTE or those prone for VTE, there appears to be no convincing data that MP help to predict or monitor VTE. However, in a recent study that investigated this issue further, looked at MP levels by a different approach by comparing percentiles of MP measured in a retrospective

of 73% indicating the need for further refinement for application in clinical practise.

syndrome (Zwaal*, et al* 2004).

research (Rak).

**3. Role in thrombosis** 

**3.1.1 Idiopathic VTE** 

**3.1 Venous Thromboembolism (VTE)** 

increased in cases of recurrence (Owen*, et al*).

In contrast to idiopathic VTE, there is strong evidence for involvement of MP in thrombogeneticity in patients with underlying immune disorders. Important examples include antiphospholipid antibody syndrome and heparin induced thrombocytopaenia with thrombosis syndromes (Combes*, et al* 1999, Dignat-George*, et al* 2004, Walenga*, et al* 2000). Markedly elevated platelet derived MP have been desccribed in both clinical syndromes (Hughes, 2000). There is experimental evidence to suggest that circulating autoantibodies trigger the formation of excess MP contributing to the prothrombotic process in these patients. Circulating MP in these syndromes have been shown to expose GPIb,GPIIbIIIa, Pselectin and thrombospondin all of which help promote thrombosis (Jy*, et al* 2007).
