Interplay between platelets and coagulation: from protective haemostasis to pathological arterial thrombosis

Junior comment:

While haemostasis is the physiological process repairing vessel injuries and preventing bleeding, atherothrombosis is a pathological condition in which a platelet-rich thrombus forms as a result of a disrupted atherosclerotic plaque. Both, haemostasis and pathological thrombus formation, are dynamic processes that rely on a coordinated interplay of platelet membrane receptors, intracellular signalling pathways, and the release of platelet proteins and inflammatory mediators.

In their State-of-the-Art review entitled "Interplay between platelets and coagulation: from protective haemostasis to pathological arterial thrombosis", Profs. Gemma Vilahur and Valentin Fuster provide a comprehensive examination of the delicate balance between haemostasis and pathological thrombosis. The authors thoroughly explore the physiological mechanisms regulating haemostasis and the pathological conditions that lead to arterial thrombosis, emphasizing the importance of early detection, attention to traditional and novel cardiovascular risk factors, and targeted therapeutic interventions.
One of the key strengths of this article is its detailed breakdown of the stages of physiological haemostasis, including vasoconstriction, primary and secondary haemostasis, and fibrinolysis. These processes work together to maintain vascular integrity, highlighting the role of platelets, coagulation factors, and endothelial cells. Importantly, an imbalance in these mechanisms can result in pathological arterial thrombosis, i.e. excessive clot formation leading to conditions such as myocardial infarction and stroke.

An interesting approach of the manuscript is the concept of ‘patient’s vulnerability’ to arterial thrombosis. According to this, in addition to plaque morphology and characteristics, arterial thrombosis is affected by systemic factors that shape the body's response to plaque disruption (pro-thrombotic state), atherosclerotic plaque burden, and plaque metabolic activity, which reflects inflammation. In this sense, the discussion on how emerging risk factors -such as inflammation, metabolic disorders, and genetic predispositions- contribute to a pro-thrombotic state provides a forward-looking perspective on cardiovascular disease prevention.
Indeed, another compelling aspect of the article is its focus on early screening and prevention. The authors advocate for the use of advanced imaging technologies to detect subclinical atherosclerosis before it leads to serious thrombotic events, which emphasizes prevention over treatment. The findings from the PESA study, highlighting the high prevalence of subclinical atherosclerosis in seemingly healthy individuals, further reinforce the need for early intervention strategies.

In summary, for healthcare professionals interested in thrombosis and haemostasis, this detailed review provides a valuable resource for understanding the intricate mechanisms of thrombus formation and potential therapeutic targets, as well as highlights promising avenues for early detection and prevention of arterial thrombosis. The expanding knowledge of thrombotic disease is expected to translate into the development of new drugs to help management and prevention of thrombosis. Hence, future research should focus on refining antithrombotic therapies -including drugs or molecules targeting FXI/FXIa, FXII/FXIIa, and GPVI- that selectively target pathological clotting without compromising physiological haemostasis.

Senior comment:

In this comprehensive review Gemma Vilahur and Valentine Fuster recapitulate and discuss the fundamental mechanisms underlying the regulation hemostasis and how its derangement leads to thrombosis. Prevention of atherothrombosis is a challenge in cardiovascular medicine and, as the Authors allude to, the preclinical stage of the atherosclerotic disease represents the time where our current knowledge should guide our clinical decisions to prevent and revert progression of atherosclerosis.