Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 12, 2025 2 hours, 24 minutes ago
Medical News: Researchers uncover how SARSCoV2 activates hidden clotting mechanisms
Scientists from the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, in collaboration with the University of Milan, have uncovered that a specific mechanism in the body known as the “contact pathway” plays a key role in causing the dangerous blood clotting problems seen in severe COVID-19 cases. Their research provides new insight into why some patients develop deadly clots even while on anticoagulant medication.
COVID-19 Contact Pathway Found to Trigger Dangerous Blood Clots
Understanding the hidden cause of COVID-19 clotting
COVID-19 is known to cause abnormal clotting that can lead to heart attacks, strokes, or pulmonary embolisms. However, scientists have long debated what actually triggers this coagulopathy. This
Medical News report highlights that instead of the well-known “extrinsic pathway,” which responds to external injury, the study found the body’s “contact pathway”—a system that can be triggered by inflammation—was excessively activated in severe COVID-19 cases.
The researchers analyzed blood samples from 111 hospitalized COVID-19 patients, divided into low, intermediate, and high-intensity care groups. They measured markers that reflect clot formation and breakdown, such as D-dimer, fibrin fragments, and fibrinolytic proteins. Surprisingly, D-dimer and fibrin degradation product levels were elevated in nearly all patients, particularly those in intensive care. But it wasn’t the usual external injury mechanism that caused it—rather, the internal contact system involving activated clotting factors FXIIa and FXIa showed significant overactivation.
The contact pathway takes center stage
The study revealed that more than 90% of patients had increased FXIIa (Factor XIIa) levels and nearly 70% had elevated FXIa (Factor XIa) levels. These enzymes are part of the body’s intrinsic clotting response and can be triggered by severe inflammation, immune activation, or the release of sticky DNA webs from immune cells known as neutrophil extracellular traps (NETs). The team discovered that these factors were more active as the severity of COVID-19 increased.
Conversely, levels of FVIIa—an enzyme that marks activation of the external injury response—were lower than normal, suggesting that COVID-19’s clotting problems arise mainly from within, not from external vessel injury. The researchers also noticed that C1 inhibitor, a natural protein that keeps the contact pathway in check, was elevated in all patients, possibly as the body’s attempt to counteract excessive clotting.
A new therapeutic window for severe COVID-19
The study’s findings shed light on why conventional blood thinners like heparin often fail to prevent clots in severe COVID-19 cases. Heparin works mainly by targeti
ng the extrinsic or downstream parts of the coagulation cascade, but not the contact pathway. By identifying that the intrinsic system is the main driver, scientists now suggest that future drugs should focus on inhibiting FXIIa or FXIa directly—both of which are currently being studied in late-stage clinical trials as safer anticoagulant options with less bleeding risk.
Potential implications beyond the pandemic
The researchers emphasized that this mechanism might apply not only to COVID-19 but also to other inflammatory or viral diseases that trigger similar immune-driven clotting. Even though five years have passed since the pandemic began, COVID-19 remains an important model for understanding how inflammation and coagulation interact.
Overall, this research provides a foundation for designing new targeted therapies that could prevent blood clots without increasing bleeding risks. By blocking the contact pathway, doctors may soon be able to treat severe COVID-19 and other thromboinflammatory conditions more effectively.
The study findings were published in the peer reviewed journal: Internal and Emergency Medicine
https://link.springer.com/article/10.1007/s11739-025-04191-z
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