Characterisation of antithrombin-dependent anticoagulants through clot waveform analysis to potentially distinguish them from antithrombin-independent inhibitors targeting activated coagulation factors
Comparative study published in Journal of clinical pathology (2020)
Abstract
AIMS: While antithrombin (AT)-independent inhibitors targeting thrombin or activated factor X have been assessed through clot waveform (CWA), there are no reports on assessment with respect to AT-dependent anticoagulants. The present study aims to characterise AT-dependent anticoagulants through CWA to distinguish them from AT-independent inhibitors. METHODS: CWA was applied to the activated partial thromboplastin time (APTT) assay of plasma samples spiked with each of AT-dependent drugs (unfractionated heparin, enoxaparin and fondaparinux) and AT-independent drugs (rivaroxaban, apixaban, edoxaban, dabigatran, argatroban, hirudin and bivalirudin), which was performed using the CS-5100 or CN-6000 (Sysmex). The APTT-CWA data were automatically gained by the analyser program. The positive mode of clotting reaction curves was defined as the direction towards fibrin generation. RESULTS: Regarding dose-response curves in AT-dependent anticoagulants, the maximum positive values of the first and secondary derivatives (Max1 and Maxp2, respectively) and the maximum negative values of the secondary derivative (Maxn2) seemed to drop to zero without making an asymptotic line, consistent with the irreversibility. Such a feature was observed also in hirudin, as reported previously. Notably, the symmetric property of Max1 peaks in the waveforms was distorted dose dependently in AT independent but not AT-dependent drugs. A plot of Maxp2 logarithm versus Maxn2 logarithm was linear. The slope was about 1 in AT-dependent drugs while that was more than 1 in AT-independent drugs. These features made it possible to distinguish AT-dependent and AT-independent drugs. CONCLUSIONS: The results aid in further understanding of the pharmacological aspects of anticoagulation and in screening of candidates for novel anticoagulants.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
While antithrombin (AT)-independent inhibitors targeting thrombin or activated factor X have been assessed through clot waveform (CWA), there are no reports on assessment with respect to AT-dependent anticoagulants.
Warum dies für die Hirudotherapie relevant ist
Diese vergleichende In-vitro-Studie nutzte die Clot Waveform Analysis (CWA) der aPTT (aktivierte partielle Thromboplastinzeit)-Bestimmung, um Antithrombin-abhängige Antikoagulanzien (z. B. Heparine, Fondaparinux) von Antithrombin-unabhängigen Inhibitoren (z. B. Rivaroxaban, Dabigatran, Argatroban, Hirudin und Bivalirudin) anhand von Plasmaproben, die mit den jeweiligen Wirkstoffen versetzt waren, zu charakterisieren und zu unterscheiden. Hirudin und Bivalirudin waren als direkte Thrombininhibitoren in der Antithrombin-unabhängigen Gruppe eingeschlossen, und die Studie beschreibt, wie sich ihre Wellenformprofile von denen AT-abhängiger Substanzen unterscheiden. Diese Laborcharakterisierung kann das Verständnis des pharmakologischen Verhaltens von Hirudin in Gerinnungsassays informieren. Die Relevanz ist indirekt: Es handelt sich um eine analytische/pharmakologische Studie ohne therapeutische oder hirudotherapeutische Anwendung, und Hirudin ist einer von vielen untersuchten Wirkstoffen und nicht der Schwerpunkt der Studie.
Zitation
Characterisation of antithrombin-dependent anticoagulants through clot waveform analysis to potentially distinguish them from antithrombin-independent inhibitors targeting activated coagulation factors
Wakui M et al. · Journal of clinical pathology, 2020
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