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Ratio of Inhibited Thrombin Generation Based on Dilute Prothrombin Time May Predict the Major Bleeding or Thrombotic Tendency in NVAF Patients Treated with Anti-Xa DOAC

1Health Sciences University of Hokkaido, Department of Internal Medicine, Ishikarigun, Japan, 2Health Sciences University of Hokkaido, Department of Clinical Laboratory, Ishikarigun, Japan, 3Hokkaido University Hospital, Division of Endoscopy, Sapporo, Japan, 4Caress Sapporo Hokko Memorial Clinic, Cardiovascular Medicine, Sapporo, Japan

Abstract Number: PB2050

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » Atrial Fibrillation

Background: During treatment with direct oral anticoagulants (DOAC) in nonvalvular atrial fibrillation (NVAF) patients, measuring their anticoagulant effects may be needed in certain circumstances to prevent major bleeding and/or refractory thrombosis.

Aims: The aim of this study is to investigate the association between major bleeding or thrombotic tendency and the laboratory tests including the clinical parameters, coagulant markers, the drug concentrations and Ratio of Inhibited Thrombin Generation (RITG) calculated using dilute prothrombin time (dPT).

Methods: Citrated plasma samples were obtained from the patients with receiving rivaroxaban (n=514), edoxaban (n=443) and apixaban (n=1081) at three sites in Japan between January 2012 and December 2019. Clinical characteristics were obtained from medical records retrospectively. The plasma concentrations of DOAC were measured by anti-Xa assay, specially calibrated for each drug. First, we compared the parameters including drug concentrations and RITG at the last visit and events between the patients with major bleeding and those without any adverse clinical event. Second, we compared RITG between the patients with or without positivity for coagulant markers such as D-dimer and fibrin monomer complex.

Results: A total of 31 major bleeding occurred, 8 in rivaroxaban, 14 in edoxaban and 9 in apixaban. In those patients, PT was longer (p< 0.001) and RITG was higher (p=0.03) compared to control group. RITG showed unique patterns of time dependent change among each DOAC (Figure1). In apixaban, RITG levels were decreasing at a slower rate over time compared to its drug concentrations and kept to some extent. Temporal RITG during treatment were higher in patients with major bleeding compared to control group in apixaban, but not in other drugs. RITG below normal range indicated higher positivity for D-dimer in apixaban.

Conclusions: RITG, calculated using dPT may indicate the tendencies for major bleeding or thrombosis by reflecting their anticoagulant effects in NVAF patients treated with DOAC, especially apixaban.


[Figure 1. Time corse of RITG (mean ± SE) among three DOAC]

To cite this abstract in AMA style:

Ohmura K, Ieko M, Naito S, Yoshida M, Takahashi N, Ono S, Sakuma I. Ratio of Inhibited Thrombin Generation Based on Dilute Prothrombin Time May Predict the Major Bleeding or Thrombotic Tendency in NVAF Patients Treated with Anti-Xa DOAC [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/ratio-of-inhibited-thrombin-generation-based-on-dilute-prothrombin-time-may-predict-the-major-bleeding-or-thrombotic-tendency-in-nvaf-patients-treated-with-anti-xa-doac/. Accessed September 24, 2023.

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