Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability

Sara Calzavarini; Justine Brodard; Claudia Quarroz; Livia Maire; Raphael Nützi; Jovana Jankovic; Laura C Rotondo; Evelyne Giabbani; Georg Martin Fiedler; Michael Nagler; Anne Angelillo-Scherrer

doi:10.1002/rth2.12238

Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: Normal values and variability

Res Pract Thromb Haemost. 2019 Jul 18;3(4):758-768. doi: 10.1002/rth2.12238. eCollection 2019 Oct.

Authors

Sara Calzavarini^{1

2}, Justine Brodard¹, Claudia Quarroz^{1

2}, Livia Maire^{1

2}, Raphael Nützi¹, Jovana Jankovic¹, Laura C Rotondo¹, Evelyne Giabbani¹, Georg Martin Fiedler³, Michael Nagler^{1

2}, Anne Angelillo-Scherrer^{1

2}

Affiliations

¹ Department of Hematology and Central Hematology Laboratory, Inselspital Bern University Hospital University of Bern Bern Switzerland.
² Department for BioMedical Research University of Bern Bern Switzerland.
³ Institute of Clinical Chemistry Inselspital Bern University Hospital University of Bern Bern Switzerland.

Abstract

Background: Thrombin generation (TG) assays evaluate the balance between pro- and anticoagulant forces, to better assess bleeding and thrombotic risks. Although TG readouts obtained with the calibrated automated TG have been investigated in multiple clinical conditions, TG still needs standardization and clinical validation. The automated TG instrument ST Genesia® (STG, Stago, Asnières-sur-Seine, France) provides a normalization of TG parameters based on a reference plasma aiming to reduce the interlaboratory variability and the variability between different measurement runs.

Objectives: To evaluate STG in a group of healthy adults.

Methods: Reference intervals in healthy adults and variability of the new standardized reagents for bleeding (BleedScreen) and thrombophilic (ThromboScreen) conditions were determined using STG.

Results: TG was measured in platelet-free plasma (PFP) samples of 123 healthy adults. Reference intervals were determined for TG parameters. Intra- and interassay coefficients of variation were calculated on quality controls and PFP samples from healthy adults. Oral contraception (OC) possibly influenced TG parameters, resulting in a higher median and a broader reference interval for peak height and endogenous thrombin potential (ETP) in women aged 20 to 49 years than in all other sex and age categories. Therefore, we propose the following reference interval categories: men, women aged <50 years not using OC, women aged <50 years using OC, and women aged ≥50 years. Normalization was effective to reduce the interassay variability of quality controls for ETP (BleedScreen assay), and peak height and ETP (ThromboScreen assay without thrombomodulin), but had little impact on PFP sample variability.

Conclusion: STG appears suitable for accurate measurement of TG in healthy adults.

Keywords: blood coagulation factors; clinical laboratory tests; quality control; reference ranges; thrombin generation.