Blood clots that form in veins—known as venous thromboembolism (VTE)—are a leading cause of illness and death worldwide. Despite the serious threat they pose to human health, however, researchers have never fully understood why these clots develop in some people but not others. A new study led by researchers at the University of Minnesota School of Public Health (SPH) sheds light on this mystery by identifying previously unknown blood proteins that may help predict these life-threatening blood clots.

To conduct the study, researchers analyzed data from more than 20,000 adults across four long-term studies, tracking participants for between 10 and 29 years. Using advanced technology to analyze blood proteins, researchers measured thousands of proteins in blood samples collected at the start of the studies and examined how those protein levels related to future risk of VTE. The findings were then tested in a separate group of nearly 40,000 participants (from the UK Biobank) to confirm the results.

The study, published in Circulation—a leading journal in the field of cardiovascular health—found:

• New blood proteins that may signal risk of VTE. The study identified 23 proteins linked to VTE risk, including 15 that had not previously been associated with blood clots.
• Other biological pathways linked to VTE. Many of these proteins are involved in processes like immune function, inflammation, and tissue repair—not just blood clotting—suggesting broader drivers of VTE risk.
• Potential causal links. Genetic analyses suggested that some of the newly discovered proteins may play a direct role in causing VTE, rather than simply signaling risk.

“This work is an important step toward understanding the biological drivers of this dangerous and potentially life-threatening condition,” said Weihong Tang, SPH professor and lead author. “By looking across thousands of proteins in large populations over time, we were able to uncover new biological pathways that may contribute to venous thromboembolism. These findings open the door to better understanding who is at risk for this condition, and could ultimately help guide more effective prevention and treatment strategies to improve patient outcomes.”

Tang also noted that the study’s scale and design strengthen its conclusions. Unlike earlier research, which often examined smaller groups or limited sets of proteins, this analysis used a prospective approach to track people over time before they developed clots, and validated results in independent populations.

The authors note that future research should confirm these findings in more diverse populations and further investigate how these proteins contribute to blood clot formation. The study also notes that additional work is needed to translate these discoveries into clinical tools that can better predict risk and guide prevention and treatment.