Thrombin generation and D-dimer concentrations in a patient cohort investigated for venous thromboembolism. Relations to venous thrombosis, factor V Leiden and prothrombin G20210A. The LIST study

Thromb Res. 2009 Jun;124(2):178-84. doi: 10.1016/j.thromres.2008.12.033. Epub 2009 Feb 20.


Introduction: The present study evaluated possible relations between various markers of thrombin generation, D-dimer and venous thromboembolism in outpatients with and without the FV Leiden and the protrombin mutations.

Patients and methods: Our cohort consisted of 98 patients with the FV Leiden and 15 with the prothrombin mutation and an equal number of age- and gender-matched controls. All subjects were investigated due to suspicion of venous thromboembolism and the diagnosis was objectively confirmed or refuted.

Results: We compared the D-dimer values and the thrombin generation markers among different patient groups (with/without thromboembolism, with/without genetic factors, gender-linked). The only statistically significant difference noted was prolonged time both for the initiation and termination of thrombin generation in patients with thrombosis. This applied to controls and to patients heterozygous for the FV Leiden. Additionally, the D-dimer values were elevated in patients with the FV Leiden. No difference was found among the patients with prothrombin mutation and their controls.

Discussion: Multi-variant analysis indicated that the difference in D-dimer between FV Leiden patients and controls was due to the greater number of patients with confirmed thrombosis in the former group, a finding supported by an independent prospective study on postoperative thrombosis. Neither D-dimer concentration nor thrombin generation depend on FV Leiden. The total amount of thrombin generated was not related to diagnosis. The prolonged thrombin generation noted in controls and FV Leiden heterozygotes with thrombosis may point out different thrombin generation profiles in different patient populations and requires further studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated Protein C Resistance / genetics
  • Case-Control Studies
  • Cohort Studies
  • Factor V / analysis*
  • Factor V / genetics
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Fibrin Fibrinogen Degradation Products / genetics
  • Genetic Markers
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Outpatients
  • Prothrombin / genetics*
  • Sex Factors
  • Specimen Handling / methods
  • Sweden / epidemiology
  • Thrombin / analysis
  • Thrombin / genetics
  • Venous Thromboembolism / diagnosis*
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / genetics*
  • Venous Thrombosis / genetics*


  • Fibrin Fibrinogen Degradation Products
  • Genetic Markers
  • factor V Leiden
  • fibrin fragment D
  • Factor V
  • Prothrombin
  • Thrombin