Blood clotting protein’s hidden complexity revealed

The new study shows that fibrinogen does not exist as a single, fixed molecule, as long believed. Instead, it can take on multiple forms that may be optimised for different functions.

This discovery advances fundamental understanding of the clotting process and may help improve how clotting conditions such as deep vein thrombosis, pulmonary embolism, stroke and bleeding disorders, are assessed and managed.

Fibrinogen helps stop bleeding by forming clots when injury occurs. Until now, scientists thought it had a stable structure held together by chemical links known as disulfide bonds.

However, the study, published in Protein Science, found that these links are more dynamic than expected. Small variations in how they form allow fibrinogen to change shape, creating different versions of the protein with distinct functions. Some forms appear to be more likely to participate in clot formation, while others may serve different roles depending on the body’s needs.

“Our findings show that fibrinogen exists in many different forms, which may increase functional versatility,” said lead study author Dr Aster Pijning from the Centenary Institute’s Centre for Biomedical AI.

“This shifts our understanding of fibrinogen from a single uniform protein to a diverse family of molecules with different functional properties.”

Dr Pijning said the findings highlight the need to better understand how fibrinogen is measured and interpreted in both research and clinical settings.

“Standard laboratory tests may not detect all forms of fibrinogen, meaning some clinically important variations could be overlooked,” she said.

“Better capturing this diversity, could over time, lead to a more accurate picture of how clotting is working in individual patients, supporting improved assessment and more personalised care, and potentially inform new treatment approaches in the future.”

The study was led by Dr Aster Pijning, with co-author Dr Diego Butera and senior author Professor Philip Hogg, all from the Centenary Institute.