Associations between complement pathways activity, mannose-binding lectin, and odds of unprovoked venous thromboembolism

Thromb Res. 2018 Sep:169:50-56. doi: 10.1016/j.thromres.2018.06.019. Epub 2018 Jun 30.


Introduction: Deep vein thrombosis (DVT) originates in the valvular sinuses of large veins in a local milieu characterized by stasis and severe hypoxia. This may induce complement- and coagulation activation, which potentially increases the risk of venous thromboembolism (VTE). The aim of the present study was to investigate whether the activity of the complement pathways, the level of mannose-binding lectin (MBL) and tissue-factor (TF) induced thrombin generation were associated with risk of unprovoked VTE.

Methods: A case-control study was performed in patients with unprovoked VTE (n = 24) and age- and sex-matched healthy controls (n = 24). Serum complement pathway activity was measured by the total complement screen assay (Wieslab®). MBL was quantified by ELISA. Plasma TF-induced thrombin generation was measured using the CAT-assay.

Results: Activity in the highest quintile of the classical pathway was associated with increased odds of unprovoked VTE (OR 4.5, 95% CI; 0.8-24.7). Moreover, MBL deficiency (≤100 ng/ml) was associated with unprovoked VTE (OR 3.5, 95% Cl; 0.8-15.3). VTE patients had shortened TF-induced lag-time (4.8 ± 0.6 min vs. 5.8 ± 2.1 min, p < 0.001) and a higher endogenous thrombin potential (ETP) (1383 ± 267 nM∗h vs. 1265 ± 247 nM∗h, p = 0.07) than controls. No association between the classical complement pathway activity or MBL deficiency, and parameters of TF-induced thrombin generation was observed.

Conclusion: Our findings suggest that high activity of the classical complement pathway, and MBL deficiency, might be associated with an increased odds of unprovoked VTE, independent of activation of TF-induced coagulation.

Keywords: Complement; Thrombin generation; Tissue factor; Venous thrombosis.

MeSH terms

  • Adult
  • Aged
  • Blood Coagulation
  • Case-Control Studies
  • Complement Activation*
  • Female
  • Humans
  • Male
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Lectin / deficiency*
  • Mannose-Binding Lectin / immunology*
  • Metabolism, Inborn Errors / blood
  • Metabolism, Inborn Errors / complications*
  • Metabolism, Inborn Errors / immunology
  • Middle Aged
  • Thrombin / immunology
  • Thromboplastin / immunology
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / immunology


  • Mannose-Binding Lectin
  • Thromboplastin
  • Thrombin

Supplementary concepts

  • Mannose-Binding Protein Deficiency