Clotting test results correlate better with DOAC concentrations when expressed as a "Correction Ratio"; results before/after extraction with the DOAC Stop reagent

Tom Exner, Julien Favresse, Sarah Lessire, Jonathan Douxfils, François Mullier

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Clotting test results are currently not useful for estimating direct oral anti-coagulant (DOAC) concentrations because baseline results vary. DOAC Stop is a DOAC extracting agent with no effect on clotting factors. We investigated if aPTT (activated partial thromboplastin time) and dRVVT (dilute Russells viper venom time) results might correlate better with DOAC concentrations if results after DOAC extraction were used to estimate a "before/after" value (Correction Ratio).

MATERIALS AND METHODS: We used activated partial thromboplastin time (aPTT, PTT-LA) and dilute Russells viper venom time clotting test (dRVVT) results previously recorded on DOAC patient plasmas (25 dabigatran, 15 apixaban, 19 rivaroxaban) without known thrombotic risk factors before and after DOAC extraction. DOAC concentrations had been determined by standard chromogenic assays.

RESULTS: Correlations between aPTT and dabigatran, apixaban, and rivaroxaban concentrations were initially poor (0.64, 0.15 and 0.39 respectively). However, they improved significantly to 0.94, 0.89 and 0.80 when the ratios of initial aPTT to the aPTT obtained after DOAC extraction were plotted against DOAC concentration. Still better correlations (0.99, 0.97, 0.95) and much higher sensitivities to the DOACs were obtained when dRVVT (LA Confirm) tests were used following this procedure on the same samples.

CONCLUSIONS: The correlations of aPTT and dRVVT tests with DOAC concentrations were significantly improved by using the ratio of result "before" to those "after" DOAC extraction. The results indicate that dRVVT (especially LA Confirm) and similar tests might be useful for determining DOAC concentrations more reliably and with better sensitivity than currently possible with clotting tests.

Original languageEnglish
Pages (from-to)69-72
Number of pages4
JournalThrombosis Research
Volume179
DOIs
Publication statusE-pub ahead of print - 2019

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Coagulants
Partial Thromboplastin Time
Prothrombin Time
Blood Coagulation Factors

Keywords

  • DOACs
  • Dabigatran
  • Apixaban
  • Rivaroxaban
  • Activated partial thromboplastin time
  • aPTT
  • Dilute Russells viper venom time
  • dRVVT
  • DOAC Stop
  • correction ratio

Cite this

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title = "Clotting test results correlate better with DOAC concentrations when expressed as a {"}Correction Ratio{"}; results before/after extraction with the DOAC Stop reagent",
abstract = "INTRODUCTION: Clotting test results are currently not useful for estimating direct oral anti-coagulant (DOAC) concentrations because baseline results vary. DOAC Stop is a DOAC extracting agent with no effect on clotting factors. We investigated if aPTT (activated partial thromboplastin time) and dRVVT (dilute Russells viper venom time) results might correlate better with DOAC concentrations if results after DOAC extraction were used to estimate a {"}before/after{"} value (Correction Ratio).MATERIALS AND METHODS: We used activated partial thromboplastin time (aPTT, PTT-LA) and dilute Russells viper venom time clotting test (dRVVT) results previously recorded on DOAC patient plasmas (25 dabigatran, 15 apixaban, 19 rivaroxaban) without known thrombotic risk factors before and after DOAC extraction. DOAC concentrations had been determined by standard chromogenic assays.RESULTS: Correlations between aPTT and dabigatran, apixaban, and rivaroxaban concentrations were initially poor (0.64, 0.15 and 0.39 respectively). However, they improved significantly to 0.94, 0.89 and 0.80 when the ratios of initial aPTT to the aPTT obtained after DOAC extraction were plotted against DOAC concentration. Still better correlations (0.99, 0.97, 0.95) and much higher sensitivities to the DOACs were obtained when dRVVT (LA Confirm) tests were used following this procedure on the same samples.CONCLUSIONS: The correlations of aPTT and dRVVT tests with DOAC concentrations were significantly improved by using the ratio of result {"}before{"} to those {"}after{"} DOAC extraction. The results indicate that dRVVT (especially LA Confirm) and similar tests might be useful for determining DOAC concentrations more reliably and with better sensitivity than currently possible with clotting tests.",
keywords = "DOACs, Dabigatran, Apixaban, Rivaroxaban, Activated partial thromboplastin time, aPTT, Dilute Russells viper venom time, dRVVT, DOAC Stop, correction ratio",
author = "Tom Exner and Julien Favresse and Sarah Lessire and Jonathan Douxfils and Fran{\cc}ois Mullier",
note = "Copyright {\circledC} 2019 Elsevier Ltd. All rights reserved.",
year = "2019",
doi = "10.1016/j.thromres.2019.04.028",
language = "English",
volume = "179",
pages = "69--72",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Elsevier",

}

TY - JOUR

T1 - Clotting test results correlate better with DOAC concentrations when expressed as a "Correction Ratio"; results before/after extraction with the DOAC Stop reagent

AU - Exner, Tom

AU - Favresse, Julien

AU - Lessire, Sarah

AU - Douxfils, Jonathan

AU - Mullier, François

N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.

PY - 2019

Y1 - 2019

N2 - INTRODUCTION: Clotting test results are currently not useful for estimating direct oral anti-coagulant (DOAC) concentrations because baseline results vary. DOAC Stop is a DOAC extracting agent with no effect on clotting factors. We investigated if aPTT (activated partial thromboplastin time) and dRVVT (dilute Russells viper venom time) results might correlate better with DOAC concentrations if results after DOAC extraction were used to estimate a "before/after" value (Correction Ratio).MATERIALS AND METHODS: We used activated partial thromboplastin time (aPTT, PTT-LA) and dilute Russells viper venom time clotting test (dRVVT) results previously recorded on DOAC patient plasmas (25 dabigatran, 15 apixaban, 19 rivaroxaban) without known thrombotic risk factors before and after DOAC extraction. DOAC concentrations had been determined by standard chromogenic assays.RESULTS: Correlations between aPTT and dabigatran, apixaban, and rivaroxaban concentrations were initially poor (0.64, 0.15 and 0.39 respectively). However, they improved significantly to 0.94, 0.89 and 0.80 when the ratios of initial aPTT to the aPTT obtained after DOAC extraction were plotted against DOAC concentration. Still better correlations (0.99, 0.97, 0.95) and much higher sensitivities to the DOACs were obtained when dRVVT (LA Confirm) tests were used following this procedure on the same samples.CONCLUSIONS: The correlations of aPTT and dRVVT tests with DOAC concentrations were significantly improved by using the ratio of result "before" to those "after" DOAC extraction. The results indicate that dRVVT (especially LA Confirm) and similar tests might be useful for determining DOAC concentrations more reliably and with better sensitivity than currently possible with clotting tests.

AB - INTRODUCTION: Clotting test results are currently not useful for estimating direct oral anti-coagulant (DOAC) concentrations because baseline results vary. DOAC Stop is a DOAC extracting agent with no effect on clotting factors. We investigated if aPTT (activated partial thromboplastin time) and dRVVT (dilute Russells viper venom time) results might correlate better with DOAC concentrations if results after DOAC extraction were used to estimate a "before/after" value (Correction Ratio).MATERIALS AND METHODS: We used activated partial thromboplastin time (aPTT, PTT-LA) and dilute Russells viper venom time clotting test (dRVVT) results previously recorded on DOAC patient plasmas (25 dabigatran, 15 apixaban, 19 rivaroxaban) without known thrombotic risk factors before and after DOAC extraction. DOAC concentrations had been determined by standard chromogenic assays.RESULTS: Correlations between aPTT and dabigatran, apixaban, and rivaroxaban concentrations were initially poor (0.64, 0.15 and 0.39 respectively). However, they improved significantly to 0.94, 0.89 and 0.80 when the ratios of initial aPTT to the aPTT obtained after DOAC extraction were plotted against DOAC concentration. Still better correlations (0.99, 0.97, 0.95) and much higher sensitivities to the DOACs were obtained when dRVVT (LA Confirm) tests were used following this procedure on the same samples.CONCLUSIONS: The correlations of aPTT and dRVVT tests with DOAC concentrations were significantly improved by using the ratio of result "before" to those "after" DOAC extraction. The results indicate that dRVVT (especially LA Confirm) and similar tests might be useful for determining DOAC concentrations more reliably and with better sensitivity than currently possible with clotting tests.

KW - DOACs

KW - Dabigatran

KW - Apixaban

KW - Rivaroxaban

KW - Activated partial thromboplastin time

KW - aPTT

KW - Dilute Russells viper venom time

KW - dRVVT

KW - DOAC Stop

KW - correction ratio

U2 - 10.1016/j.thromres.2019.04.028

DO - 10.1016/j.thromres.2019.04.028

M3 - Article

VL - 179

SP - 69

EP - 72

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

ER -