Study of thrombin generation with St Genesia to evaluate xaban pharmacodynamics: Analytical performances over 18 months

Foulon-Pinto, Geoffrey; Jourdi, Georges; Perrin, Julien; Abdoul, Johan; Paris, Guillaume; Gouin‐Thibault, Isabelle; Curis, Emmanuel; Lecompte, T.; Siguret, Virginie

doi:10.1111/ijlh.13443

Cited by 9 publications

(23 citation statements)

References 28 publications

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“…Since the measurement of TG has been fully automatized on the ST Genesia analyzer, TG curves can now also be acquired in clinical laboratories ( 12 , 13 , 44 – 47 ). Therefore, we investigated TD analysis using ST Genesia TG data to establish normal ranges for TD parameters in an apparently healthy population.…”

Section: Discussionmentioning

confidence: 99%

Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay

Carlo

Yan²,

Cate³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThe haemostatic balance is an equilibrium of pro- and anticoagulant factors that work synergistically to prevent bleeding and thrombosis. As thrombin is the central enzyme in the coagulation pathway, it is desirable to measure thrombin generation (TG) in order to detect possible bleeding or thrombotic phenotypes, as well as to investigate the capacity of drugs affecting the formation of thrombin. By investigating the underlying processes of TG (i.e., prothrombin conversion and inactivation), additional information is collected about the dynamics of thrombin formation.ObjectivesTo obtain reference values for thrombin dynamics (TD) analysis in 112 healthy donors using an automated system for TG.MethodsTG was measured on the ST Genesia, fibrinogen on the Start, anti-thrombin (AT) on the STA R Max and α2Macroglobulin (α2M) with an in-house chromogenic assay.ResultsTG was measured using STG-BleedScreen, STG-ThromboScreen and STG-DrugScreen. The TG data was used as an input for TD analysis, in combination with plasma levels of AT, α2M and fibrinogen that were 113% (108–118%), 2.6 μM (2.2 μM−3.1 μM) and 2.9 g/L (2.6–3.2 g/L), respectively. The maximum rate of the prothrombinase complex (PCmax) and the total amount of prothrombin converted (PCtot) increased with increasing tissue factor (TF) concentration. PCtot increased from 902 to 988 nM, whereas PCmax increased from 172 to 508 nM/min. Thrombin (T)-AT and T-α2M complexes also increased with increasing TF concentration (i.e., from 860 to 955 nM and from 28 to 33 nm, respectively). PCtot, T-AT and T-α2M complex formation were strongly inhibited by addition of thrombomodulin (−44%, −43%, and −48%, respectively), whereas PCmax was affected less (−24%). PCtot, PCmax, T-AT, and T-α2M were higher in women using oral contraceptives (OC) compared to men/women without OC, and inhibition by thrombomodulin was also significantly less in women on OC (p < 0.05).ConclusionsTG measured on the ST Genesia can be used as an input for TD analysis. The data obtained can be used as reference values for future clinical studies as the balance between prothrombin conversion and thrombin inactivation has shown to be useful in several clinical settings.

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Section: Discussionmentioning

confidence: 99%

Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay

Carlo

Yan²,

Cate³

et al. 2022

Front. Cardiovasc. Med.

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“…However, the variability of TG parameters is a known major issue of this technique and should also be taken into consideration. Other research has assessed STG-TS intra-and interassay variability, 24,28 which is not always reduced by normalization.…”

Section: Discussionmentioning

confidence: 99%

Thrombin generation in children using ThromboScreen reagent kit with ST Genesia—A pilot study

Gassiot

Ruiz-Llobet

Suleman

et al. 2021

Int J Lab Hematology

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The burden of VTE in children and developmental hemostasisRecent years have seen a noticeable increase in the diagnosis of venous thromboembolism (VTE) in children, probably the result of higher survival rates, increased awareness, and the use of improved imaging techniques. In hospitalized children, the rate is reported to be 58 per 10 000 admissions, 100 to 1000 times the figure observed at a population level. 1 The prevention, diagnosis, and clinical management of VTE is becoming a growing health concern. 2-5 Moreover, although some recently developed scores exist, 2,3 VTE risk assessment tools are not widely used for hospitalized children, as opposed to hospitalized adults. 6 Venous thromboembolism has multiple hemostatic driving factors, and consequently, a combination of biomarkers may be required for its risk stratification. Extrapolating adult practice approaches is

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“…Regarding the assessment of DOAC PD, the study of thrombin generation (TG) has been shown as a suitable and reliable assay to assess in vitro or ex vivo anticoagulant effect of direct FXa inhibitors in contrast to prothrombin time [30][31][32][33][34][35][36].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Assessment of DOAC in GEriatrics (Adage Study): Rivaroxaban/Apixaban Concentrations and Thrombin Generation Profiles in NVAF Very Elderly Patients

et al. 2022

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Background: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions and polypharmacy, receive direct oral anticoagulants (DOAC), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. Aims: To investigate: i/DOAC concentration-time profiles; ii/thrombin generation (TG); and iii/clinical outcomes 6-months after inclusion in very elderly AF in-patients receiving rivaroxaban or apixaban. Methods: ADAGE-NCT02464488 was an academic prospective exploratory multicenter study, enrolling AF in-patients aged 80-years, receiving DOAC for at least 4 days. Each patient had 1-5 blood samples at different time-points over 20-days. DOAC concentrations were determined using chromogenic assays. TG was investigated using ST-Genesia (STG-ThromboScreen, STG-DrugScreen). Results: We included 215 patients (women 71.1%, mean age 87±4-years), 104-rivaroxaban and 111-apixaban, 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (CV) whatever the regimen, at Cmax [49-46%] and Cmin [75-61%] in 15mg-rivaroxaban and 2.5mg-apixaban patients, respectively. Dose regimen was associated with Cmax and Cmin plasma concentrations in apixaban (p=0.0058 and p=0.0222, respectively), but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of thrombin peak-height (STG-Thromboscreen) was noticed at a given plasma concentration for both xabans, suggesting an impact of the underlying coagulation status on TG in elderly in-patients. After 6-month follow-up, major bleeding/thrombo-embolic event/death rates were 6.7%/1.0%/17.3% in rivaroxaban and 5.4%/3.6%/18.9% in apixaban patients, respectively. Conclusion: Our study provides original data in very elderly patients receiving DOAC in real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings.

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Study of thrombin generation with St Genesia to evaluate xaban pharmacodynamics: Analytical performances over 18 months

Cited by 9 publications

References 28 publications

Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay

Semi-automated thrombin dynamics applying the ST Genesia thrombin generation assay

Thrombin generation in children using ThromboScreen reagent kit with ST Genesia—A pilot study

Assessment of DOAC in GEriatrics (Adage Study): Rivaroxaban/Apixaban Concentrations and Thrombin Generation Profiles in NVAF Very Elderly Patients

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