Interplay between inflammation and thrombosis in cardiovascular pathology

Thrombosis is the most feared complication of cardiovascular diseases and a main cause of death worldwide, making it a major health-care challenge. Platelets and the coagulation cascade are effectively targeted by antithrombotic approaches, which carry an inherent risk of bleeding. Moreover, antithrombotics cannot completely prevent thrombotic events, implicating a therapeutic gap due to a third, not yet adequately addressed mechanism, namely inflammation. In this Review, we discuss how the synergy between inflammation and thrombosis drives thrombotic diseases. We focus on the huge potential of anti-inflammatory strategies to target cardiovascular pathologies. Findings in the past decade have uncovered a sophisticated connection between innate immunity, platelet activation and coagulation, termed immunothrombosis. Immunothrombosis is an important host defence mechanism to limit systemic spreading of pathogens through the bloodstream. However, the aberrant activation of immunothrombosis in cardiovascular diseases causes myocardial infarction, stroke and venous thromboembolism. The clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is supported by the increased risk of cardiovascular events in patients with inflammatory diseases but also during infections, including in COVID-19. Clinical trials in the past 4 years have confirmed the anti-ischaemic effects of anti-inflammatory strategies, backing the concept of a prothrombotic function of inflammation. Targeting inflammation to prevent thrombosis leaves haemostasis mainly unaffected, circumventing the risk of bleeding associated with current approaches. Considering the growing number of anti-inflammatory therapies, it is crucial to appreciate their potential in covering therapeutic gaps in cardiovascular diseases. In this Review, Stark and Massberg discuss how the interplay between innate immunity, platelet activation and coagulation, known as immunothrombosis, functions as a host defence mechanism to limit pathogen spreading, yet its aberrant activation, termed thromboinflammation, results in thrombotic complications, highlighting the therapeutic potential of anti-inflammatory strategies in cardiovascular pathologies.

Automated summary

Thrombosis is a major health challenge globally, with inflammation playing a crucial role in driving thrombotic diseases. Anti-inflammatory strategies show promise in targeting cardiovascular pathologies and addressing therapeutic gaps.