Targeted Metabolic Profiling in Deep Vein Thrombosis

Deep venous thrombosis (DVT) is a blood clot, usually affecting the legs, causing pain, swelling, and redness. The clot damages the veins, which can result in chronic pain, swelling and ulceration. This is called the post-thrombotic syndrome, which impacts heavily on patients' life and work. If the clot dislodges and travels to the lungs, it becomes a pulmonary embolus (PE), which can be life threatening. Together, DVT and PE affect 500,000 people in Europe every year, representing the most common preventable cause of hospital acquired death. They are expensive conditions not only due to their treatment costs, but also secondary to the resulting loss of work days and productivity.

DVT is diagnosed by clinical examination, risk scoring, usually via the Wells Score, and a blood test called D dimer, a fibrin degradation product. D-dimer is specific but not very sensitive. In other words, when the test is negative, it is unlikely that a DVT is present.

However, many conditions can raise D-dimer levels, making it less useful when positive. Duplex ultrasound can confirm the presence of clot but this can be difficult to visualize or is often not seen at all. The clot can take time to form and patients may not experience symptoms immediately. This is a problem for treatment, as new, clot-busting medication works best in the first 2 weeks after a DVT and it is currently impossible to tell when the thrombus formed.

Because of the importance of DVT, and ongoing issues regarding its diagnosis, ageing and prognosis, numerous research groups have been exploring novel candidate biomarkers to help develop a more accurate diagnostic and prognostic marker for DVT. The Section of Vascular Surgery and of Computational and Systems Medicine (CSM) at Imperial College, have had a longstanding collaboration working towards this end using metabonomics.

Metabonomics is defined as: 'the quantitative measurement of the multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification'. In other words, it examines the end products of cellular metabolism via platforms such as Nuclear Magnetic Resonance Spectroscopy (NMR) and Mass Spectrometry (MS), which are both high throughput analytical platforms. These enable the qualification (untargeted) and quantification (targeted) of different molecules in a given sample, to a degree of detail superior to that offered by other omic technologies (e.g. proteomics). Metabonomics has demonstrated clear applications in vascular disease, including chronic venous disease , atherosclerosis , venous leg ulceration, aneurysmal disease and stroke.