Research into New Molecular Mechanisms in Thrombotic Diseases Paves the Way for Innovative Therapeutic Approaches

Abstract

Thrombosis is a multifaceted process involving various molecular components, including the coagulation cascade, platelet activation, platelet-endothelial interaction, anticoagulant signaling pathways, inflammatory mediators, genetic factors and the involvement of various cells such as endothelial cells, platelets and leukocytes. A comprehensive understanding of the molecular signaling pathways and cell interactions that play a role in thrombosis is essential for the development of precise therapeutic strategies for the treatment and prevention of thrombotic diseases. Ongoing research in this field is constantly uncovering new molecular players and pathways that offer opportunities for more precise interventions in the clinical setting. These molecular insights into thrombosis form the basis for the development of targeted therapeutic approaches for the treatment and prevention of thrombotic disease. The aim of this review is to provide an overview of the pathogenesis of thrombosis and to explore new therapeutic options.

Keywords: atherosclerotic plaque; coagulation cascade; extracellular vesicles; genetic factors; inflammation; platelets; platelet–endothelial interaction; therapies; thrombosis.

Figure 1

A schematic representation of some of the newest factors that act on the endothelium to make it healthy or to lead it in a thrombotic state.

Figure 2

Interplay between the endothelium, the immune system and the hemostatic process during atherosclerotic plaque formation and subsequent rupture. Abbreviations: CD, cluster of differentiation; CD40-L, CD40 ligand; EPCR, endothelial protein C receptor; IFN-γ, interferon-γ; IL, interleukin; LDL, low-density lipoprotein; MCP-1, monocyte chemoattractant protein-1; MMP, matrix metalloproteinase; NET, neutrophil extracellular trap; NO, nitric oxide; OX-LDL, oxidized low-density lipoprotein; PAFR, platelet-activating factor receptor; PGE₂, prostacyclin; PSGL-1, P-selectin glycoprotein ligand-1; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α.

Figure 3

Completed and ongoing studies with factor XIa inhibitors in different clinical settings. Abbreviations: ACS, acute coronary syndrome; AF, atrial fibrillation; AMI, acute myocardial infarction; ASO, anti-sense oligonucleotide; DOAC, direct oral anticoagulant; ESKD, end-stage kidney disease; LMWH, low molecular weight heparin; TKA, total knee arthroplasty. Note: The OCEANIC-AF trial was prematurely interrupted for higher incidence of ischemic events in the asundexian arm compared to apixaban, and the OCEANIC-AMI trial is no longer ongoing.