Singh Tanjot, Hasan Muhammad, Gaule Thembaninkosi G, Ajjan Ramzi A
Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Woodhouse, Leeds LS2 9JT, UK.
St James's University Hospital, Beckett St, Harehills, Leeds LS9 7TF, UK.
Int J Mol Sci. 2025 Feb 5;26(3):1336. doi: 10.3390/ijms26031336.
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.
血浆蛋白纤维蛋白原对止血和伤口愈合至关重要,它是血凝块的结构基础。通过凝血因子之间的复杂相互作用,可溶性血浆纤维蛋白原转化为不溶性纤维蛋白网络,形成血凝块的骨架,这是限制血管创伤后失血的关键步骤。本综述探讨了纤维蛋白原调节出血的分子机制,重点关注其与维持纤维蛋白网络稳定性和防止过早分解的其他蛋白质的相互作用。此外,我们还阐述了纤维蛋白原通过与血小板的生理相互作用在确保血凝块稳定性方面的作用。我们讨论了纤维蛋白原在各种临床情况下的治疗应用,包括创伤性凝血病、产后出血和心脏手术。重要的是,全面了解蛋白质功能将有助于开发新的治疗方法以限制血管创伤后的失血,而血管创伤仍是全球死亡的主要原因。虽然目前的管理策略有助于处理血管损伤后的失血,但它们远非完美,未来的研究应优先完善纤维蛋白原替代策略并开发新型药物以稳定纤维蛋白网络。利用纤维蛋白原的分子特性在改善创伤护理、手术干预和产科出血的治疗效果方面具有巨大潜力。