Coagulation activation after discontinuation of VTE treatment with different oral anticoagulants and impact on 12-month clinical outcomes

Beyer‐Westendorf, Jan; Gehrisch, S.; Stange, Thoralf; Tittl, Luise; Siegert, Gabriele; Weiss, Norbert

doi:10.1016/j.thromres.2015.06.003

Cited by 6 publications

(3 citation statements)

References 22 publications

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“…Effects of oral anticoagulation on TAT complexes and PTF F1 þ 2 are ambiguous in the literature. [46][47][48][49] In our study, the preprocedural difference in PTF F1 þ 2 was extinguished after TAVI. Therefore, influence of prior oral anticoagulation on thrombin generation after TAVI seems to be rather low.…”

Section: Discussionsupporting

confidence: 51%

Impact of Transcatheter Aortic Valve Implantation on Thrombin Generation and Platelet Function

et al. 2021

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Background Transcatheter aortic valve implantation (TAVI) is an evolving treatment of severe aortic valve stenosis. However, thromboembolic events such as stroke are common, predominantly early after TAVI. Optimal periprocedural antithrombotic regime is unknown. Especially, as antithrombotic medication enhances bleeding risk, thrombin generation and platelet function are crucial in the pathogenesis of ischemic events. However, the impact of the TAVI procedure on thrombin formation and platelet reactivity is not known by now. Methods We evaluated thrombin levels using thrombin–antithrombin (TAT) complexes and prothrombin fragments (PTFs) using enzyme-linked immunosorbent assay. Furthermore, platelet reactivity was measured via light transmission aggregometry before and 2 hours after TAVI in 198 patients. Results TAT complexes and PTF F1 + 2 substantially increased during TAVI. Postprocedurally, TAT complexes and PTF were significantly higher after TAVI compared with percutaneous coronary intervention due to acute myocardial infarction, while preprocedural TAT complexes and PTF F1 + 2 did not differ. In contrast, platelet reactivity was not altered early after TAVI. Only adenosine diphosphate-induced aggregation was reduced, reflecting preprocedural loading with clopidogrel. Conclusion In this pilot study, we were able to demonstrate that thrombin generation is significantly increased early after TAVI, while platelet function is not affected. Increased thrombin concentrations may contribute to the high risk of postprocedural thromboembolic events. This leads to the hypothesis that extended peri-interventional anticoagulation early after TAVI may be an approach to reduce thromboembolic events.

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Section: Discussionsupporting

confidence: 51%

Impact of Transcatheter Aortic Valve Implantation on Thrombin Generation and Platelet Function

et al. 2021

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“…While all patients in Dulcis were receiving VKAs at enrollment, >90% of patients in Apidulcis received a DOAC (at a low dose in more than one-fourth of patients) as anticoagulant when the first D-dimer was measured. The anticoagulant action of DOACs and VKAs is based on completely different mechanisms; possible different effects on the formation and degradation of fibrin cannot be excluded, and though data on possible differences are to date missing, 23 this issue deserves further analysis. Other factors may contribute to a less constant anticoagulant effect, such as the high inter- and intraindividual variability in the drug blood concentrations, 24 , 25 and problems in adherence to treatment.…”

Section: Discussionmentioning

confidence: 99%

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study

Palareti¹,

Poli

Ageno³

et al. 2022

Blood Advances

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D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study we aimed at assessing the value of an algorithm incorporating serial D-dimer testing and administration of reduced dose apixaban (2.5 mg twice daily) only to patients with positive test. 732 outpatients aged 18 to 74 years, anticoagulated for at least 12 months after a first unprovoked VTE were included. Patients underwent D-dimer testing with commercial assays and pre-established cutoffs. If the baseline D-dimer, during anticoagulation, was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286; 39.1%) were left without anticoagulation. At first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% CI, 4.5 to 11.2), including symptomatic proximal DVT or PE recurrence, death for VTE, major bleeding, occurring in patients off anticoagulation, versus that in those receiving apixaban (1.1%; 95% CI, 0.4 to 2.6; adjusted HR, 8.2; 95% CI, 3.2 to 25.3). In conclusion, in patients anticoagulated for at least one year after a first unprovoked VTE, the decision whether to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced dose apixaban against recurrences. ClinTrials.gov: NCT03678506.

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“…26 The use of these clotting markers might be an alternative. Furthermore, thromboembolism events including ischemic stroke/SE, fibrin-related blood markers, such as soluble fibrin monomer complex and D-dimer, [48][49][50] or thrombin generation markers, such as prothrombin fragment 112 and thrombin anti-thrombin complex, 50,51 would be excellent explanatory biomarkers for event risk theoretically; however, no population models for the relationship between plasma concentrations of FXa inhibitors have been reported. The reliability of the PT-response model constructed in this study may need to be confirmed by future analysis adopting these biomarkers when they become available.…”

Section: 10mentioning

confidence: 99%

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

et al. 2018

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Key Points• Simulations suggested that the dose reduction of rivaroxaban would decrease fatal events associated with major bleeding.• Dose optimization of FXa inhibitors might further enhance their therapeutic benefit.The noninferiority of direct oral factor Xa (FXa) inhibitors (rivaroxaban, apixaban, and edoxaban) in treatment of atrial fibrillation were demonstrated compared with warfarin by several large clinical trials; however, subsequent meta-analyses reported a higher risk of major bleeding with rivaroxaban than with the other FXa inhibitors. In the present study, we first estimated the changes of prothrombin time (PT) in 5 randomized trials based on reported population pharmacokinetic and pharmacodynamic models and then carried out a model-based meta-analysis to obtain models describing the relationship between PT changes and the event rates of ischemic stroke/systemic embolism (SE) and of major bleeding. By using the models, we simulated the optimal therapeutic doses for each FXa For apixaban and edoxaban, no distinct change in the overall mortality was simulated by dose modification. This study suggested that the current dose of rivaroxaban might be excessive and would need to be reduced to decrease the excess risk of major bleeding.

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Coagulation activation after discontinuation of VTE treatment with different oral anticoagulants and impact on 12-month clinical outcomes

Cited by 6 publications

References 22 publications

Impact of Transcatheter Aortic Valve Implantation on Thrombin Generation and Platelet Function

Impact of Transcatheter Aortic Valve Implantation on Thrombin Generation and Platelet Function

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

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