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In vitro Neutralization of Unfractionated Heparin for the Measurement of Thrombin Generation with the STG-drugScreen Reagent on ST Genesia

S. Fontaine1, M. Bourdin1, M.-A. Bildan1, O. Kerleau1, M. Lambert1, F. Depasse2, O. Mathieu1

1Diagnostica Stago, Recherche Prospective R&D, Gennevilliers, France, 2Diagnostica Stago, Développement Clinique, Asnières-sur-Seine, France

Abstract Number: PB0362

Meeting: ISTH 2021 Congress

Theme: Diagnostics and OMICs » Laboratory Diagnostics

Background: The ST Genesia (STG) is a fully automated thrombin generation test (TGT) platform more standardized than the original Calibrated Automated Thrombogram (CAT) and designed to support clinical applications in the lab.
In some clinical indications such as prevention of thrombosis or ExtraCorporeal Membrane Oxygenation, patients may receive unfractionated heparin (UFH). TGT is adversely affected by UFH, thereby it cannot reflect basic haemostatic state (without the influence of heparin) in these patients, requiring UFH neutralization. Polybrene (Pb) at 25µg/mL has been shown to be effective for UFH neutralization in the original CAT system(1).

Aims: Conceive an automated TGT test using the STG-DrugScreen reagent neutralizing UFH and allowing to restore basic TGT parameters.
Select between Pb and Heparinase I (Hep) the best neutralizing agent based on test performances: dose-response effect, neutralization performances on UFH-spiked samples and on board stability.

Methods: Neutralizing agent (Pb or Hep) was added at different concentrations to the reconstituted STG-DrugScreen reagent.
Normal Pooled Plasma (NPP) and twelve donors’ leftover plasma samples were spiked with UFH. NPP was spiked with five different levels of sodium unfractionated heparin (HNa) and two levels of calcium heparin (HCa) to cover the STA-Liquid anti-Xa measuring range of 0-1.08IU/mL (Table 1).

Performances Sample UFH Anti-Xa Concentrations Neutralizing agent Analytical Result
Dose-response NPP ≤ 0.10 IU/mL Pb: 0 – 210 µg/mL;
6 levels
Hep: 0 – 1.6 IU/mL;
7 levels
Relative deviation to STG-DrugScreen TGT baseline
Neutralization performance on spiked NPP Heparin-spiked plasmas HNa: 0 – 1.08 IU/mL;
6 levels
HCa: 0 – 1.07 IU/mL;
3 levels
Pb: 0 – 210 µg/mL;
6 levels
Hep: 0 – 1.6 IU/mL;
7 levels
Relative deviation to STG-DrugScreen TGT baseline
On-board stability of modified STG-DrugScreen Heparin-spiked plasmas HNa: 0 – 0.8 IU/mL;
3 levels
Pb: 25 µg/mL
Hep: 1.2 IU/mL
Relative deviation of STG-DrugScreen TGT parameters at T4 hours versus T0
Neutralization performance on donor samples Donors’ leftover plasma samples spiked with HNa HNa: 0 – 0.8 IU/mL;
12 samples
Pb: 25 µg/mL Relative deviation to STG-DrugScreen TGT parameters before versus after heparin neutralization

Evaluation of neutralizing agents in STG-DrugScreen reagent with citrated plasma samples.

Results: Table 2 provides summary of assay performances.

Performances Results
Dose-response Pb had no significant impact for Pb at concentrations < 150µg/mL (< 10%).
Hep had minimal impact (< 10%) on TGT of NPP regardless to the tested concentrations.
Neutralization performance on heparin-spiked NPP 25 µg/mL of Pb or 1.2 IU/mL of Hep completely neutralized the effect of both HNa and HCa UFH on TGT.
On board stability of modified STG-DrugScreen With 25 µg/mL of Pb or 1.2 IU/mL of Hep, on board stability relative deviation to reference time was less than 8% for all parameters except 11% for NPP Lag Time with Hep.
On board stability with 25 µg/mL of Pb was up to 4h.
Neutralization performance on donor samples Relative deviation to STG-DrugScreen was less than 8% with 25 µg/mL pf Pb, except for one donor sample which shifted to a more rapid TGT up to 14% Lag Time reduction.

Summary of performance evaluation.

Conclusions: Our results show that 25µg/mL of Pb or 1.2IU/mL of Hep can completely neutralize the anticoagulant effect of UFH up to 1.08IU/mL. At these concentrations, TGT parameters measured in NPP were not impacted. Pb showed slightly better on-board stability than Hep.
These in vitro results indicate that Pb or Hep can be used added to STG-DrugScreen reagent to automatically neutralize UFH for TGT measurement on STG with a four-hour reagent on-board stability. This allows to abolish heparin interference and assess the basic TGT profile of a patient.

(1) Carlo A et al. ISTH 2009 PP-WE-164

To cite this abstract in AMA style:

Fontaine S, Bourdin M, Bildan M-, Kerleau O, Lambert M, Depasse F, Mathieu O. In vitro Neutralization of Unfractionated Heparin for the Measurement of Thrombin Generation with the STG-drugScreen Reagent on ST Genesia [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/in-vitro-neutralization-of-unfractionated-heparin-for-the-measurement-of-thrombin-generation-with-the-stg-drugscreen-reagent-on-st-genesia/. Accessed September 29, 2023.

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