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Open AccessArticle

Delayed Thrombin Generation Is Associated with Minor Bleedings in Venous Thromboembolism Patients on Rivaroxaban: Usefulness of Calibrated Automated Thrombography

1
Department of Coronary Artery Disease and Heart Failure, Jagiellonian University Medical College, John Paul II Hospital, 80 Pradnicka Street, 31-202 Krakow, Poland
2
Department of Biochemistry, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405-0068, USA
3
Department of Experimental Cardiac Surgery, Anesthesiology and Cardiology, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka Street, 31-202 Krakow, Poland
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2018; https://doi.org/10.3390/jcm9072018
Received: 11 May 2020 / Revised: 12 June 2020 / Accepted: 22 June 2020 / Published: 27 June 2020
(This article belongs to the Special Issue Venous Thromboembolism — Diagnosis, Prevention and Treatment)
Bleeding is the most feared and difficult to predict adverse event of anticoagulation. We sought to investigate whether calibrated automated thrombography (CAT) parameters are associated with minor bleeding (MB) in anticoagulated patients following venous thromboembolism (VTE). Enrolled were 132 patients on rivaroxaban, 145 on vitamin K antagonists (VKA) and 31 controls who stopped anticoagulation. Prior to the next dose of the anticoagulant, we measured CAT parameters, along with rivaroxaban concentration and INR. During a median follow-up of 10 months, we recorded minor and major bleedings. On rivaroxaban, 27 (20.5%) patients with MB had longer time to start thrombin generation, lower peak thrombin generation and lower endogenous thrombin potential compared with subjects without MB (all p < 0.001). All CAT parameters, except for peak thrombin generation (p = 0.049), were similar in VKA patients with (n = 25, 17.2%) vs. without MBs. By logistic regression, time to start thrombin generation (p = 0.007) and unprovoked VTE (p = 0.041) independently predicted MBs on rivaroxaban. Major bleedings were more frequent in patients with MBs (17.3% vs. 1.8%, p < 0.001). Abnormal CAT parameters characterize VTE patients prone to MBs on rivaroxaban, but not on VKA. Time to start thrombin generation measured about 24 h since the last rivaroxaban dose might help predict MBs. View Full-Text
Keywords: venous thromboembolism; minor bleeding; calibrated automated thrombography; rivaroxaban; vitamin K antagonist venous thromboembolism; minor bleeding; calibrated automated thrombography; rivaroxaban; vitamin K antagonist
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Zalewski, J.; Stepien, K.; Nowak, K.; Caus, S.; Butenas, S.; Undas, A. Delayed Thrombin Generation Is Associated with Minor Bleedings in Venous Thromboembolism Patients on Rivaroxaban: Usefulness of Calibrated Automated Thrombography. J. Clin. Med. 2020, 9, 2018.

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