**5.2 Prognostic**

The potential for MP as a prognostic tool is dependent on reliable, reproducible and easily available tools to measure microparticles. There is emerging data that MP may predict VTE in cancer patients and may be able to provide prognostic information in several other conditions.

## **5.3 Therapeutic**

An interesting dimension to this area is the approach to use or modify MP for therapeutic benefit. The possibility of bioengineered and/or harvested membrane microparticles in tissue repair or angiogenesis is being investigated (Soleti, 2009). The MP are also being studied as a drug delivery tool (Benameur, 2009). Microparticles could potentially be specifically targeted to reduce or prevent thrombotic complications or end organ damage (Myers, 2005). This is an promising and exciting new area for researchers and clinicians working in this area.

Microparticles have therefore emerged as key role players in vascular biology and pathophysiology of thrombosis. They remain an important research tool and their clinical applications are being actively investigated with potential to be applied in diagnostic, prognostic and therapeutic arenas. They are small yet powerful effectors for the pathophysiology of the endovascular system.

#### **6. References**

Pathophysiology and Clinical Aspects of 12 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

however, the clinical utility of this approach is also as yet unkown (Howes ; Ramacciotti).

There are several outstanding issues such as standardization of preanalytical and analytical variables as well as integration of the various approaches in measuring MP. Several novel approaches are now being considered. 'Megamix beads' is novel approach to standardizing of gating of microparticles using flow cytometry. It uses a mix of a 0.9um and 0.3um sized beads to try and capture all events within the gate set by the beads (Robert, 2009 ;Robert, 2011). One of the problems of using this approach is the lack of linearity in the relationship between the size of beads and forward sctatter at that particle size. A recent commercially available nanoscale technology known as 'Nanosight' has incorporated antibody tagging of small particles for accurate identification and counting in this size range (Harrison, 2009).

Utility of Measuring MP in venous thromboembolism is yet to be fully established . The case for measuring MP in cancer related VTE is perhaps stronger. There are three areas within which the potential for detecting and measuring MP with respect to venous

The evidence for using measurement of MP in a diagnostic setting is limited. The studies so far have shown variable results depending on whether TF bearing MP, functional activity or total MP were measured. With respect to VTE MP have been assessed in the paradigm of VTE, diagnosis in a small pilot study where it was shown that D-dimer, P-selectin and total MP levels predicted thrombosis as demonstrated on Doppler ultrasound (Ramacciotti; Rectenwald, 2005). The role of MP in diagnosis of VTE warrants confirmation in prospective cohort studies. The standardization of measurement of MP will go a long way in ensuring

The potential for MP as a prognostic tool is dependent on reliable, reproducible and easily available tools to measure microparticles. There is emerging data that MP may predict VTE in cancer patients and may be able to provide prognostic information in several other

An interesting dimension to this area is the approach to use or modify MP for therapeutic benefit. The possibility of bioengineered and/or harvested membrane microparticles in tissue repair or angiogenesis is being investigated (Soleti, 2009). The MP are also being studied as a drug delivery tool (Benameur, 2009). Microparticles could potentially be specifically targeted to reduce or prevent thrombotic complications or end organ damage (Myers, 2005). This is an promising and exciting new area for researchers and clinicians

Automated devices to analyse MP are also being developed (Wagner, 2010).

**4.4 Measuring microparticles: Future directions** 

**5. Conclusions** 

**5.1 Diagnostic** 

**5.2 Prognostic** 

conditions.

**5.3 Therapeutic** 

working in this area.

thromboembolism may be relevant.

comparability of such studies.


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**2** 

*Slovenia* 

**Hyperhomocysteinemia: Relation to** 

Homocysteine is a sulphur-containing amino acid, which structurally is closely related to the essential amino acids methionine and cysteine. The cellular methylation cycle performs the metabolism of methionine and since homocysteine is an intermediate within this cycle, the body in this way is provided with all organic homocysteine. The term homocysteine is used to define the combined pool of homocysteine, homocystine, and mixed disulfide compounds (Fig. 1) even involving homocysteine thiolactone a cyclic form which is often

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found in the plasma of patients with hyperhomocisteinemia.

Fig. 1. Structural formulae of homocysteine

**1. Introduction** 

**Cardiovascular Disease and** 

**Venous Thromboembolism** 

*University of Primorska, College of Health Care Izola,* 

Nadja Plazar and Mihaela Jurdana

