Is Plasma Mannose-Binding Lectin a Clue to Higher VTE Risk?

Elevated levels of mannose-binding lectin (MBL) in patient plasma hint at an increased risk for future venous thromboembolism (VTE), as uncovered by international investigators published in the American Heart Association’s Arteriosclerosis, Thrombosis, and Vascular Biology.

From the Trøndelag Health Study, or HUNT Study, the investigators examined a population-based case cohort of 294 patients with VTE in 1,066 sex- and age-weighted sub-cohorts. They measured patients’ plasma levels using the SomaScan 7k aptamer-based platform.

Plasma MBL circulates in complex with MBL-associated serine proteases (MASPs), and with a venous thrombosis formation site, can promote thrombin generation. Therefore, the investigators also performed in vitro assessments in patient plasma of thrombin produced by MBL-MASPs complexes.

The investigators categorized the study cohort patients into quartiles by MBL level. From multivariable-adjusted Cox proportional hazards regression models, they determined that patients in the highest quartile had 79% greater risk for overall VTE than patients in the lowest quartile, with an estimated hazard ratio of 1.79. In patients with high plasma MBL, they calculated an especially pronounced risk for both deep vein thrombosis and unprovoked VTE, with estimated hazard ratios of 2.50 and 2.81, respectively.

On their in vitro assessments, the investigators observed that MBL-MASP-1/2 complexes accelerated both complement activation and thrombin generation, and that monospecific inhibitors halted their enzymatic activity. This suggested to the investigators that high MBL levels’ association with heightened risk for future VTW is connected to MBL-MASP-1/2 complex activity.

Reference

Damoah CE, Valderhaug SM, Snir O, et al. Elevated plasma MBL levels are associated with risk of future venous thromboembolism: HUNT. Arterioscler Thromb Vasc Biol. Published online May 15, 2025. doi:10.1161/ATVBAHA.124.322052