Plasma Concentrations of High Molecular Weight Kininogen and Prekallikrein and Venous Thromboembolism Incidence in the General Population

Thromb Haemost. 2019 May;119(5):834-843. doi: 10.1055/s-0039-1678737. Epub 2019 Feb 19.


The kallikrein/kinin system, an intravascular biochemical pathway that includes several proteins involved in the contact activation system of coagulation, renin-angiotensin activation and inflammation, may or may not play a role in venous thromboembolism (VTE) occurrence. Within a large prospective population-based study in the United States, we conducted a nested case-cohort study to test the hypothesis that higher plasma levels of high molecular weight kininogen (HK) or prekallikrein are associated with greater VTE incidence. We related baseline enzyme-linked immunosorbent assay measures of HK and prekallikrein in 1993 to 1995 to incidence VTE of the lower extremity (n = 612) through 2015 (mean follow-up = 18 years). We found no evidence that plasma HK or prekallikrein was associated positively with incident VTE. HK, in fact, was associated inversely and significantly with VTE in most proportional hazards regression models. For example, the hazard ratio of VTE per standard deviation higher HK concentration was 0.88 (95% confidence interval = 0.81, 0.97), after adjustment for several VTE risk factors. Our findings suggest that plasma levels of these factors do not determine the risk of VTE in the general population.

MeSH terms

  • Blood Coagulation
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Kallikrein-Kinin System
  • Kininogen, High-Molecular-Weight / blood*
  • Male
  • Middle Aged
  • Plasma / metabolism*
  • Population Groups*
  • Prekallikrein / metabolism*
  • Prospective Studies
  • Risk
  • United States / epidemiology
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / metabolism*


  • Kininogen, High-Molecular-Weight
  • Prekallikrein