Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

Maag, Anja; Rein, Nienke van; Schuijt, Tim J.; Kopatz, Wil F.; Kruijswijk, Daniëlle; Thomassen, Stella; Hackeng, Tilman M.; Camire, Rodney M.; Poll, Tom van der; Meijers, Joost C. M.; Bos, Mettine H.A.; Veer, Cornelis van ’t

doi:10.1111/jth.15589

Cited by 5 publications

(2 citation statements)

References 34 publications

(105 reference statements)

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“…They concluded that factor Xa-mediated activation of factor V represents a specific thrombin generation activation pathway during coagulation initiation, a process that may be particularly important among anticoagulated patients with major bleeding. 32 Taken together, these findings suggest that correcting kinetic TGA parameters, in addition to quantitative parameters, may be relevant with respect to predicting a meaningful hemostatic effect. The mean LT in plasma from healthy volunteers ranges from 1.9 to 2.3 minutes when measured using CAT.…”

Section: Study Methodsmentioning

confidence: 75%

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

Shaw

Unachukwu

Cyr

et al. 2023

TH Open

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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.

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Section: Study Methodsmentioning

confidence: 75%

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

Shaw

Unachukwu

Cyr

et al. 2023

TH Open

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“…The other intrinsic process involves a membrane-bound tenase complex composed of factor IXa, its cofactor factor VIIIa, and calcium ions activating factor X on the platelet surface. Factor Xa then triggers prothrombin to thrombin, resulting in blood coagulation [140]. A Factor X homolog was revealed to cleave the viral S protein at the S1/S2 boundary, allowing the virus to enter host cells [141].…”

Section: Factor Xamentioning

confidence: 99%

Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Oubahmane

Hdoufane

Bjij

et al. 2022

CTMC

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The outbreak of the SARS-CoV-2 virus in late 2019 and the spread of the COVID-19 pandemic have caused severe health and socioeconomic damage worldwide. Despite the significant research effort to develop vaccines, antiviral treatments, and repurposed therapeutics to effectively contain the catastrophe, there are no available effective vaccines or antiviral drugs that are able to limit the threat of the disease, so the infections continue to expand. To date, the search for effective treatment remains a global challenge. Therefore, it is imperative to develop therapeutic strategies to contain the spread of SARS-CoV-2. Like other coronaviruses, SARS-CoV-2 invades and infects human host cells via the attachment of its spike envelope glycoprotein to the human host cell receptor hACE2. Subsequently, several host cell proteases facilitate viral entry via proteolytic cleavage and activation of the S protein. These host cell proteases include, type II transmembrane serine proteases (TTSPs), cysteine cathepsins B and L, furin, trypsin, and Factor Xa among others. Given the critical role of the host cell proteases in coronavirus pathogenesis, their inhibition by small molecules has successfully targeted SARS-CoV-2 in vitro, suggesting that host cell proteases are attractive therapeutic targets for SARS-CoV-2 infection. In this review, we focus on the biochemical properties of host cell proteases that facilitate the entry of SARS-CoV-2, and we highlighted therapeutic small molecule candidates that have been proposed through in silico research.

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Catechol-chitosan/carboxymethylated cotton-based Janus hemostatic patch for rapid hemostasis in coagulopathy

Qiu

et al. 2023

Carbohydrate Polymers

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Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 5 publications

References 34 publications

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

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

Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Catechol-chitosan/carboxymethylated cotton-based Janus hemostatic patch for rapid hemostasis in coagulopathy

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