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CC BY-NC-ND 4.0 · TH Open 2023; 07(03): e229-e240
DOI: 10.1055/s-0043-1771300
Trial Protocol Design Paper

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale

Joseph R. Shaw 
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
,
Ubabuko Unachukwu
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
,
Joseph Cyr
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
,
Deborah M. Siegal
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
,
Lana A. Castellucci
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
,
Patrick Van Dreden
3   Diagnostica Stago, Gennevilliers, France
,
Dar Dowlatshahi
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
4   Brain and Mind Research Institute, Ottawa, Canada
,
Hakan Buyukdere
5   Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada
,
Timothy Ramsay
2   Ottawa Hospital Research Institute, Ottawa, Canada
,
Marc Carrier
1   Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Canada
2   Ottawa Hospital Research Institute, Ottawa, Canada
› Author Affiliations Funding The GAUGE study is funded by a Clinical Research Grant through the PSI Foundation (Grant #20-15; Application ID 2020-1438), and by in-kind support from Diagnostica Stago, which facilitated thrombin generation assay testing at their central clinical research laboratory. Dr. Siegal is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease. Dr. Castellucci is a member of the Canadian Venous Thromboembolism Research Network (CanVECTOR); the Network received grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). Dr. Castellucci holds a Heart and Stroke Foundation of Canada National New Investigator Award, and a Tier 2 research Chair in Thrombosis and Anticoagulation Safety from the University of Ottawa.
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Abstract

Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain.

Objective GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery.

Methods Laboratory outcomes will include the mean paired change in TGA parameters from pre- to post-PCC administration and the proportion of participants whose post-PCC TGA values fall within a defined reference range. Clinical outcomes will include hemostatic efficacy, thromboembolic complications, and all-cause death at 30 days post-PCC.

Conclusion Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding.

Keywords

hemostasis - factor Xa inhibitors - dabigatran - anticoagulation reversal

Supplementary Material



Publication History

Received: 21 March 2023

Accepted: 12 June 2023

Article published online:
25 July 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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