Complement activation assessed by the plasma terminal complement complex and future risk of venous thromboembolism

Area of Science:

• Complement system activation
• Thrombosis and hemostasis research
• Molecular epidemiology

Background:

• The role of complement system activation, measured by plasma TCC, in predicting future venous thromboembolism (VTE) risk is not well understood.
• Investigating plasma TCC as a potential biomarker for VTE is crucial for risk stratification.

Purpose of the Study:

• To determine the association between plasma TCC levels and the incidence of VTE.
• To explore potential genetic underpinnings of plasma TCC levels using exome sequencing data.

Main Methods:

• A nested case-control study within the Tromsø cohort included 415 VTE cases and 848 controls.
• Logistic regression models analyzed the association between plasma TCC quartiles and VTE risk.
• Whole exome sequencing was performed to identify genetic variants.

Main Results:

• VTE risk increased significantly with higher quartiles of plasma TCC, particularly for unprovoked VTE.
• Individuals in the highest TCC quartile had a 1.74-fold increased odds of unprovoked VTE compared to the lowest quartile.
• A higher VTE risk was observed with samples collected closer to the event, but no genome-wide association was found between gene variants and plasma TCC.

Conclusions:

• Elevated plasma TCC levels are associated with an increased risk of VTE, especially unprovoked events.
• No significant association was identified between genetic variants and plasma TCC levels, suggesting other regulatory mechanisms.
• Plasma TCC may serve as a predictive biomarker for VTE risk.