Thrombin generation profile in non-thrombotic factor V Leiden carriers

  • Paul BilloirEmail author
  • Thomas Duflot
  • Marielle Fresel
  • Marie Hélène Chrétien
  • Virginie Barbay
  • Véronique Le Cam Duchez


Factor V Leiden (FVL) mutation is the most common genetic risk factor for venous thromboembolism. In families with a history of thrombosis, FVL can be present in 18%. Thrombin generation test is commonly used as an evaluation tool of thrombotic risk. The objective of this study was to evaluate the thrombogenic potential of FVL in asymptomatic carriers and in patients with personal or familial history of thrombosis. This was a retrospective single center study including 160 patients. Among them, 43 had personal history of thrombosis and 117 had familial history of thrombosis. Thrombin generation (TG) was realized in frozen platelet poor plasma with 1 pM of tissue factor and 4 µM of phospholipid. FVL mutation was associated with a global increase of TG. No difference was observed between patients with provoked thrombosis and patients with first-degree familial history of thrombosis (endogenous thrombin potential (ETP): 1501.0 ± 316.4 nM min and thrombin peak: 253.4 ± 71.5 nM vs. 1520.4 ± 283.8 nM min and 268.6 ± 68.0 nM). An increase of TG was observed in patients with unprovoked thrombosis (n = 23) and in patients with provoked thrombosis (n = 20) (ETP: 1819.5 ± 319.8 nM min and peak: 332.3 ± 55.8 nM). In the unprovoked thrombosis group, patients with a pulmonary embolism had a higher ETP than patients with deep vein thrombosis (DVT) (2036 ± 343 nM min vs. 1707 ± 261 nM min). With a predictive score formula (s = 0.1315 × Age + 0.0105 × ETP) with a threshold of 22.1 as risk to develop an unprovoked thrombosis among patients with second-degree familial history. The results of our analysis suggest that measurement of thrombin generation in patients with FVL mutation may identify subjects with an increased risk of unprovoked thrombosis. Further studies are needed to examine the usefulness of predicting thrombotic presentation in asymptomatic carriers.


Factor V Leiden mutation Thrombin generation Unprovoked thrombosis Hypercoagulable states Asymptomatic carrier 



The authors are grateful to Nikki Sabourin-Gibbs, Rouen University Hospital, for editing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors state that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11239_2019_1821_MOESM1_ESM.tif (43 kb)
Supplementary material 1 (TIF 42 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Normandie Univ, UNIROUEN, INSERM U1096, Rouen University HospitalRouenFrance
  2. 2.Department of Pharmacology, CHU de RouenRouenFrance
  3. 3.INSERM U1096, Normandie University, UNIROUENRouenFrance
  4. 4.Rouen University HospitalRouenFrance
  5. 5.Service d’Hématologie BiologiqueCentre Hospitalier Universitaire Charles NicolleRouenFrance

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