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Thrombin generation test as a marker for high risk venous thrombosis pregnancies

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Abstract

Pregnancy is a well-established risk factor for venous thromboembolism and is associated with a state of hypercoagulability. The use of sensitive and specific biological markers to predict risk factors for thrombosis is essential during pregnancy. Our objective was to investigate the usefulness of thrombin generation test (TGT) as a marker to predict the risk of thrombosis in high risk venous thrombosis (HRVT) pregnancies compared to normal pregnancies. This retrospective study enrolled 134 women with HRVT pregnancies, 78 of whom had monozygotic, spontaneous and untreated pregnancies and formed the study group. The control group comprised 106 women with normal pregnancies. Routine assessment of coagulation activation markers: fibrinogen, d-dimer, prothrombin fragments 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and fibrin monomer complexes (FMC) was performed every 5 weeks in the study group to detect a possible pathological state of hypercoagulability. TGT was performed using platelet-free plasma, 1 and 5 pM tissue factor (TF), supplemented by phospholipids (PL) ± thrombomodulin. Fibrinogen, d-dimer, F1 + 2, and TAT, but not FMC, increased significantly throughout pregnancy in both groups but no difference was shown between the groups. TGT showed an early increase in thrombin generation in both groups, which stabilized during the second month of pregnancy. No correlation was demonstrated between thrombin generation parameters and coagulation activation markers. Based on our results, TGT did not prove conclusive as a marker to predict the risk of thrombosis in HRVT pregnancies. Finding a sensitive and specific biological marker to predict thrombosis risk requires further investigation.

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Abbreviations

APL:

Antiphospholipid

AT:

Antithrombin

ETP:

Endogenous thrombin potential

F1 + 2:

Prothrombin fragments 1 + 2

FMC:

Fibrin monomer complexes

FVL:

Factor V Leiden

G20210A-FII:

Prothrombin G20210A

HRVT:

High risk venous thrombosis

LMWH:

Low molecular weight heparin

PC:

Protein C

PE:

Pulmonary embolism

PFP:

Platelet free plasma

PS:

Protein S

TAT:

Thrombin–antithrombin complexes

TF:

Tissue factor

TG:

Thrombin generation: TG

TGT:

Thrombin generation test: TGT

TM:

Thrombomodulin

VTE:

Venous thromboembolism

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Acknowledgements

The authors would like to thank Agnes Deshayes for technical assistance. We are indebted to Nikki Sabourin-Gibbs, Rouen University Hospital, for her help in editing the manuscript.

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Authors and Affiliations

  1. Department of Biological Hematology, Rouen University Hospital, F 76000, Rouen, France

    Bérangère S. Joly, Bénédicte Sudrié-Arnaud & Jeanne-Yvonne Borg

  2. Hôpital Lariboisière, Service d’Hématologie Biologique, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Paris, France

    Bérangère S. Joly

  3. Normandie Univ, UNIROUEN, Inserm 1096, Department of Biological Hematology, Rouen University Hospital, F 76000, Rouen, France

    Virginie Barbay & Véronique Le Cam Duchez

Authors
  1. Bérangère S. Joly
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  2. Bénédicte Sudrié-Arnaud
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Correspondence to Véronique Le Cam Duchez.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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

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Joly, B.S., Sudrié-Arnaud, B., Barbay, V. et al. Thrombin generation test as a marker for high risk venous thrombosis pregnancies. J Thromb Thrombolysis 45, 114–121 (2018). https://doi.org/10.1007/s11239-017-1572-3

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