Influence of direct oral anticoagulants on thrombin generation on Ceveron TGA

Pfrepper, Christian; Behrendt, Lisa-Charlott; Bönigk, Hagen; Siegemund, T.; Metze, Michael; Franke, Dirk; Petros, Sirak; Siegemund, A.

doi:10.1111/ijlh.13721

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…Pfrepper et al observed a moderate nonlinear correlation between thrombin generation parameters and NOACs levels (rivaroxaban and apixaban). 42 However, no patients with APS were included. Further research in this area is strongly required.…”

Section: Microvascular Thrombosismentioning

confidence: 99%

Thrombotic Antiphospholipid Syndrome and Direct Oral Anticoagulants: Unmet Needs and Review of the Literature

Marco-Rico

Marco

2023

Semin Thromb Hemost

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Patients with thrombotic antiphospholipid syndrome (APS) require long-term anticoagulation due to the high-thrombotic recurrence risk. Vitamin K antagonists (VKA) have been traditionally considered the standard of care in thrombotic APS. Nevertheless, the risk of recurrence persists with VKA. There are publications considering different intensities of anticoagulation with VKA; however, the standard-intensity anticoagulation (international normalized ratio between 2.0 and 3.0) is the most recommended. Furthermore, there is no consensus on the role of antiplatelet treatment in thrombotic APS. Nonvitamin K antagonist oral anticoagulants (NOACs) have emerged as an alternative to VKA for many indications. There are, however, discrepancies regarding the management with NOACs in thrombotic APS. In this review, we update the different clinical trials with NOACs in venous, arterial, and microvascular thrombosis and suggest how these patients should be managed in agreement with the expert panels. Although scarce data are published regarding the current role of NOACs in thrombotic APS, the clinical trials failed to demonstrate noninferiority of NOACs compared with VKA, especially in patients with triple antiphospholipid antibodies positivity and/or arterial thrombosis. Single or double antiphospholipid positivity should be analyzed on a case-by-case basis. In addition, we focus on different areas of uncertainty that still remain in thrombotic APS and NOACs. To summarize, emerging clinical trials are needed to provide robust data on the management of thrombotic APS.

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Section: Microvascular Thrombosismentioning

confidence: 99%

Thrombotic Antiphospholipid Syndrome and Direct Oral Anticoagulants: Unmet Needs and Review of the Literature

Marco-Rico

Marco

2023

Semin Thromb Hemost

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“…Further studies showed that apixaban and rivaroxaban have a non-linear inhibitory function for thrombin generation. This indicates that most thrombin generation inhibition occurs at low anti-Xa concentrations (i.e., with a low concentration of DOAC, thrombin generation is still inhibited) ( 175 , 176 ). Therefore, the authors further investigated how much thrombin was generated 12 h after intake of a DOAC.…”

Section: Thrombosismentioning

confidence: 99%

Thrombin generation assays to personalize treatment in bleeding and thrombotic diseases

Valke

Rijpma

Meijer

et al. 2022

Front. Cardiovasc. Med.

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Treatment of bleeding and thrombotic disorders is highly standardized and based on evidence-based medicine guidelines. These evidence-based treatment schemes are well accepted but may lead to either insufficient treatment or over-dosing, because the individuals’ hemostatic properties are not taken into account. This can potentially introduce bleeding or thrombotic complications in individual patients. With the incorporation of pharmacokinetic (PK) and pharmacodynamic (PK-PD) parameters, based on global assays such as thrombin generation assays (TGAs), a more personalized approach can be applied to treat either bleeding or thrombotic disorders. In this review, we will discuss the recent literature about the technical aspects of TGAs and the relation to diagnosis and management of bleeding and thrombotic disorders. In patients with bleeding disorders, such as hemophilia A or factor VII deficiency, TGAs can be used to identify patients with a more severe bleeding phenotype and also in the management with non-replacement therapy and/or bypassing therapy. These assays have also a role in patients with venous thrombo-embolism, but the usage of TGAs in patients with arterial thrombosis is less clear. However, there is a potential role for TGAs in the monitoring of (long-term) antithrombotic therapy, for example with the use of direct oral anticoagulants. Finally this review will discuss controversies, limitations and knowledge gaps in relation to the introduction of TGAs to personalize medicine in daily medical practice.

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Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies

Josset,

Rezigue,

Dargaud

2024

Int J Lab Hematology

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Hematology laboratories have traditionally monitored hemophilia replacement therapy by measuring coagulation factors before and after infusion. However, new drugs that do not rely on the replacement of the deficient factor require new approaches to laboratory monitoring, as factor VIII (FVIII) or factor IX (FIX) assays are no longer adequate. Non‐factor therapies come in many different forms, that have one thing in common: they all increase thrombin generation. Their main adverse effect is thrombosis which may occur when too much thrombin is formed. This is the perfect mirror image of anticoagulant treatment, which always diminishes the amount of thrombin formed and has bleeding as its main adverse effect. Thrombin‐forming capacity is decreased in congenital bleeding disorders and increased in prothrombotic conditions, indicating it governs bleeding and thrombosis. Therefore, the thrombin generation assay (TGA) is a logical tool for monitoring non‐factor therapies, offering a comprehensive assessment of hemostatic balance. TGA identifies patients with severe bleeding, helps to optimize bypassing therapy, and detects hypercoagulability, making it ideal for guiding and monitoring hemophilia treatment with non‐factor therapies. It also assesses the efficacy and safety of combined therapies, including non‐factor therapies with bypassing agents or FVIII/FIX concentrates. The purpose of this paper is to review the current state of knowledge regarding the use of TGA to monitor novel hemophilia therapies. It will address controversies, limitations, and knowledge gaps related to the integration of TGA into personalized medicine in routine clinical practice.

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Influence of direct oral anticoagulants on thrombin generation on Ceveron TGA

Cited by 5 publications

References 27 publications

Thrombotic Antiphospholipid Syndrome and Direct Oral Anticoagulants: Unmet Needs and Review of the Literature

Thrombotic Antiphospholipid Syndrome and Direct Oral Anticoagulants: Unmet Needs and Review of the Literature

Thrombin generation assays to personalize treatment in bleeding and thrombotic diseases

Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies

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