The Gilded Clot: Review of Metal-Modulated Platelet Activation, Coagulation, and Fibrinolysis

The processes of blood coagulation and fibrinolysis that in part maintain the physical integrity of the circulatory system and fluidity of its contents are complex as they are critical for life. While the roles played by cellular components and circulating proteins in coagulation and fibrinolysis are widely acknowledged, the impact of metals on these processes is at best underappreciated. In this narrative review we identify twenty-five metals that can modulate the activity of platelets, plasmatic coagulation, and fibrinolysis as determined by in vitro and in vivo investigations involving several species besides human beings. When possible, the molecular interactions of the various metals with key cells and proteins of the hemostatic system were identified and displayed in detail. It is our intention that this work serve not as an ending point, but rather as a fair evaluation of what mechanisms concerning metal interactions with the hemostatic system have been elucidated, and as a beacon to guide future investigation.

Automated summary

This narrative review highlights the importance of the processes of blood coagulation and fibrinolysis in maintaining the integrity of the circulatory system and fluidity of its contents, and sheds light on the underappreciated impact of metals on these processes. Through in vitro and in vivo investigations, the authors identify twenty-five metals that can modulate platelet activity, plasmatic coagulation, and fibrinolysis, and provide detailed insights into the molecular interactions between these metals and key cells and proteins of the hemostatic system. The review aims to serve as a comprehensive evaluation of the current understanding of metal interactions with the hemostatic system, and as a guide for future research.