You may only associate these tiny cells with their role in blood clotting, but how can we use them as early-warning systems for life-threatening disease? Dr. Chris Jones shares the details of his latest (and previous) research.
Your body, much like it does with the rest of your cells, is almost constantly killing and regenerating your platelets. While they only have a lifespan of about ten days, their effects are expansive and powerful. The processes by which our blood coagulates are dynamic, complex; a chain reaction of sorts. Biologists often label these events as ‘haemostasis’ - the pathway to stopping ourselves from bleeding.
At a critical point in our coagulation ‘chain reaction’, platelets gather at sites of damage in response to particular ‘agonists’ (molecules which activate platelet aggregation), forming a clump called a ‘thrombus’. But these tiny cells don’t always behave as predictably. Some will stick to others. Some are swept away by the stream of blood into the body’s circulatory highways. Some are not even activated. Recent research by Associate Professor Chris Jones focuses on what happens to these rogue cells.
It turns out, the platelets comprising a thrombus are surprisingly diverse. Whether the platelets are being activated for the first time, have been activated before, or are resting in a stable state similar to ‘quiescence’, the local thrombogenic populations of these cells may have some influence over the physiology (functioning) and pathologies (disorders) of the blood system.
Let’s say your platelets are not following instructions when signalled to a site where you’ve cut yourself. If they are inappropriately forming a thrombus within blood vessels, such a thrombus can break free and lodge itself somewhere such as the brain or the lungs. Many cases of strokes or pulmonary embolisms (artery blockage within the lungs) can be attributed to such thrombi finding themselves in places they shouldn’t be.
This is where Chris’s research comes in. Given what we know about how activated platelets behave in the haemostasis pathway, being able to manipulate their function would give us an edge in the battle against vascular dementia, strokes, cardiovascular disease, and bleeding disorders. The traits of a given platelet – its age, how readily it’s activated, or how it responds to anti-platelet drugs – are hugely diverse if you look at any given thrombus. As a result, the same drug treatment to control overactive platelets won’t always have the same effect.
It's thought that tens of millions of people every year are prescribed some form of anti-platelet medication without having their platelet function assessed first. So why aren’t we measuring platelet function and characteristics as a biomarker of disease? In other words, can the appearance of a patient’s platelets offer us clues to what’s going on inside their vascular architecture? Only recently has this possibility become a reality.
In collaboration with Bath University and the University of Reading’s Department of Pharmacy, Chris and his colleagues have developed an early means of screening people for these types of disorders. The test takes the familiar design of a dipstick for blood samples. On closer inspection, it’s made of strips with built-in capillaries, or fine tubes, coated with molecules which can trigger platelet activation. In a nutshell, the ‘height’ to which blood runs up the capillaries tells us the strength of platelet activation. An effective inhibitor of platelet activation will mean that the sampled blood will not rise as far up the capillary tubes. Comparing blood samples with varying concentrations of anti-platelet drugs, we can also assess how effective they are for a given individual, determining whether the treatment is right for them.
His rationale is that if there were some ways of comparing the platelets between different people (of any age, gender, genetic factors, ethnicity and/or lifestyle), we would have another diagnostic tool to add to our arsenal, making chosen treatments more effective. Such testing would allow clinicians to pick out patients who would respond best to anti-platelet medications.
The intention is to use this type of test in larger populations, to make larger comparisons between individuals. Although still in its infancy, the technique shows a lot of potential. Chris hopes to use these principles to correlate platelet function and appearance to changes in genetics – will someone’s platelet profile predispose them to suffering from certain health conditions? Perhaps. The final hurdle, according to Chris, is condensing this into a cheap technique which gives fast results, allowing more people to be screened.
This isn’t the first time Chris has seen his work influencing actual clinical practice. A paper published back in 2004 described the effects of ‘multiple’ anti-platelet therapy for people receiving carotid endarterectomies – a surgery that removes deposits of fat from the carotid artery in the neck, to minimise the risk of a stroke. This procedure isn’t flawless; taking away these deposits leaves behind a highly thrombogenic surface. In other words, platelets can still bind to the inside of the artery and aggregate into thrombi which, of course, can become dislodged and cause embolisms and/or strokes within the brain. Every patient in the study had already been given aspirin (an anti-platelet drug). When used in tandem with heparin (an anti-clotting drug), the incidence of post-surgery strokes declined hugely – it was adopted as standard practice.
It’s research like this that allows clinical practices to evolve, shaping the way patients are cared for and making us more alert to changes in the way our body functions, which can give rise to life-changing disease.
I wanted to know what advice Chris could offer to those wanting to embark on their own research journey. His answer was simple: make sure it’s something you’re passionate about. What could this be for you? How will you go about finding your niche? And remember, the quality of your work will only ever be as good as your interest in the topic.
Coagulation Cascade - Diagram credit Isla Bailey
Stages of Platelet Activation: 1. Inactive platelets take a smooth, discoid shape. 2. Once activated, they change shape and develop pseudopodia, which are thin outward projections of membrane that help it adhere to the collagen surface. 3. Once adhered, platelets occupy a lamellipodia form, where it loses all projections, and spreads out to aid coverage. - Image credit Isla Bailey
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