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

Aaron R. Folsom, Weihong Tang, Saonli Basu, Jeffrey R. Misialek, David Couper, Susan R. Heckbert, Mary Cushman

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)834-843
Number of pages10
JournalThrombosis and Haemostasis
Volume119
Issue number5
DOIs
StatePublished - 2019

Keywords

  • high molecular weight kininogen
  • prekallikrein
  • prospective study
  • pulmonary embolus
  • venous thrombosis

PubMed: MeSH publication types

  • Journal Article

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