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Updated: May 16, 2025

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Elevated Plasma MBL Levels Are Associated With Risk of Future Venous Thromboembolism: The HUNT Study

Christabel Esi Damoah1, Solveig M Valderhaug1, Omri Snir1,2

  • 1Thrombosis Research Center, Department of Clinical Medicine (C.E.D., S.M.V., O.S., S.K.B., T.E.M., J.-B.H.), UiT-The Arctic University of Norway, Tromsø.

Arteriosclerosis, Thrombosis, and Vascular Biology
|May 15, 2025
PubMed
Abstract

Insights

High levels of mannose-binding lectin (MBL) are linked to a significantly increased risk of venous thromboembolism (VTE). This elevated risk appears to be partly due to MBL-associated serine proteases initiating thrombin generation.

Area of Science:

  • Immunology
  • Complement System
  • Thrombosis

Background:

  • Mannose-binding lectin (MBL) is a pattern recognition molecule that activates the lectin complement pathway.
  • MBL circulates with MBL-associated serine proteases (MASPs) and can facilitate thrombin generation.
  • Binding of MBL to pathogens or altered host cells initiates these processes.

Purpose of the Study:

  • To investigate the association between plasma MBL levels and the future risk of venous thromboembolism (VTE).
  • To explore the role of MBL-MASP-1/2 complexes in promoting thrombin generation.

Main Methods:

  • A population-based case-cohort study (HUNT study) involving 294 VTE patients and 1066 subcohorts.
  • Plasma MBL levels were quantified using a SomaScan 7k aptamer-based platform.
  • Cox proportional hazards regression models were used to assess VTE risk, and in vitro assays examined thrombin generation by MBL-MASP complexes.

Main Results:

  • Individuals in the highest quartile of MBL levels had a 79% increased risk of overall VTE compared to the lowest quartile.
  • High MBL levels were strongly associated with increased risk for deep vein thrombosis (HR 2.50) and unprovoked VTE (HR 2.81).
  • MBL-MASP-1/2 complexes were shown to promote complement activation and thrombin generation in vitro.

Conclusions:

  • Elevated plasma MBL levels are associated with a higher risk of future VTE.
  • The increased VTE risk may be partly mediated by MBL-MASP-1/2 complexes initiating thrombin generation at the site of clot formation.
Keywords:
MASPcohort studiescomplementdeep vein thrombosishumansmannose binding lectinvenous thrombosis

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