Exploiting the Molecular Properties of Fibrinogen to Control Bleeding Following Vascular Injury

The plasma protein fibrinogen is critical for haemostasis and wound healing, serving as the structural foundation of the blood clot. Through a complex interaction between coagulation factors, the soluble plasma fibrinogen is converted to insoluble fibrin networks, which form the skeleton of the blood clot, an essential step to limit blood loss after vascular trauma. This review examines the molecular mechanisms by which fibrinogen modulates bleeding, focusing on its interactions with other proteins that maintain fibrin network stability and prevent premature breakdown. Moreover, we also cover the role of fibrinogen in ensuring clot stability through the physiological interaction with platelets. We address the therapeutic applications of fibrinogen across various clinical contexts, including trauma-induced coagulopathy, postpartum haemorrhage, and cardiac surgery. Importantly, a full understanding of protein function will allow the development of new therapeutics to limit blood loss following vascular trauma, which remains a key cause of mortality worldwide. While current management strategies help with blood loss following vascular injury, they are far from perfect and future research should prioritise refining fibrinogen replacement strategies and developing novel agents to stabilise the fibrin network. Exploiting fibrinogen's molecular properties holds significant potential for improving outcomes in trauma care, surgical interventions and obstetric haemorrhage.