Briefing Therapeutic Approaches in Anticoagulant, Thrombolytic, and Antiplatelet Therapy
Debarshi Kar Mahapatra, Sanjay Kumar Bharti in Medicinal Chemistry with Pharmaceutical Product Development, 2019
Currently available direct factor Xa inhibitors are rivaroxaban, apixaban, and edoxaban (Figure 7.7). Rivaroxaban is given orally. It can inhibit both free factor Xa and factor Xa bound in the prothrombinase complex. Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade by inhibiting both thrombin formation and development of thrombi [48]. Apixaban is a highly selective; orally bioavailable and reversible direct inhibitor of free and clot-bound factor Xa. It was approved in Europe in 2012. Subsequently, it was approved in the U.S. in 2014 for treatment and secondary prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE) [49].
Fibrinolytic Enzymes for Thrombolytic Therapy
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Factor Xa is a serine protease and since it is part of prothrombinase complex, it carries crucial role in blood coagulation. Factor Xa inhibitors are another class of anticoagulant drugs reducing thrombin formation. These small molecules bind with active site of factor X (Xa), which in turn inhibits the formation of thrombin. They demonstrate varying structural and functional diversity and can be either naturally occurring or synthetic molecule and chemically it can be peptide, protein, or heparin saccharidic sequences (Fareed et al., 1999; Leone et al., 2004; Bauer, 2006; Samama et al., 1999). Their mode of action could be either direct by binding to factor Xa or indirect through binding with antithrombin III (AT), leading to Factor Xa inactivation. The interaction of Xa inhibitors could be reversible or irreversible (Harenberg and Fenyvesi, 2004; Walenga et al., 2002). Fondaparinux is a heparin pentasaccharide, the FDA approved this for its use after surgery and also for initial management of thrombotic disorders such as pulmonary embolism and deep vein thrombosis trials (Hoppensteadt et al., 2008). Another indirect-acting FXa inhibitor is Idraparinux (SANORG-34006), which is a hyper methylated variant of fondaparinux and showed more affinity towards antithrombin III (AT) (PERSIST investigators, 2004). Rivaroxaban was an orally active, direct thrombin inhibitor and extensively studied for its use in preventing venous thromboembolism during knee and hip replacement (Turpie et al., 2005; Eriksson et al., 2006). A few other direct Factor Xa inhibitors include otamixaban, apixaban, edoxaban, etc. Although most of the Factor Xa inhibitors are either under clinical trial or in different developmental stages, still they are considered safer than thrombin inhibitors (Hoppensteadt et al., 2008).
Preanesthetic evaluation
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Essentials of Anesthesia for Neurotrauma, 2018
However, the other direct factor Xa inhibitors still present a challenge. In a retrospective study of 18 TBI patients with intracranial or subarachnoid hemorrhage who were taking rivaroxaban or apixaban, PCC was a good option to potentially reduce hematoma expansion.5 Andexanet alfa, Xa inhibitor, and ciraparantag, Xa factor, and II factor inhibitors are in phase III clinical trials.
A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK
Published in Current Medical Research and Opinion, 2023
Alexander T. Cohen, Gary Benson, Charlotte A. Bradbury, Satarupa Choudhuri, Nathan Hutchinson Jones, Anthony Maraveyas, Balaji Venugopal, Annie M. Young, Chris Chapman, Shauna McIntyre, Danny Burney, Kevin G. Pollock, Angharad R. Morgan, Peter D. Gabb, Raza Alikhan
Direct factor Xa inhibitors can be prescribed to patients at any stage of cancer, though locally spread and metastatic cancers are at a greater risk of recurrent VTE and of major bleeding events with anticoagulation treatment47. We suggest advanced stage cancer patients may be treated with direct factor Xa inhibitors according to an individualized risk-benefit profile of recurrence and bleeding risk. We also consider LMWH to be the preferred first-line option in acutely unwell and/or unstable hospitalized patients, as LMWH have fewer DDIs than direct factor Xa inhibitors43. They also have a shorter half-life and can be administered in patients with organ dysfunction, thrombocytopenia, or in need of an invasive procedure, with easier dose management if necessary. For more stable outpatients, we consider direct factor Xa inhibitors to be a more suitable long-term option.
Managing patients on direct factor Xa inhibitors with rapid thrombelastography
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2021
Andrea Bak Kaaber, Øivind Jans, Morten H. Dziegiel, Jakob Stensballe, Pär I. Johansson
The current change in demography with an increased proportion of elderly citizens results in thromboembolic complications becoming more common and, hence, also the need for antithrombotic medications. Since its introduction in the 1950s vitamin K antagonists (VKAs) has been the drug of choice [1] and guidelines for its use developed. Important drawbacks of VKA therapy are the need for frequent monitoring and that its anticoagulative effect is influenced significantly by food intake. In the beginning of the twenty first century direct oral anti-coagulants (DOAC) were introduced [2] and its use has increased rapidly [3]. DOAC encompass two classes of drugs with different mechanisms of action; rivaroxaban and apixaban are direct coagulation factor Xa inhibitors [2] and dabigatran is a direct thrombin inhibitor [4]. The present study focuses on the use of the direct factor Xa inhibitors rivaroxaban and apixaban (XABANs). XABANs have extensively replaced the use of VKAs as thromboprophylaxis mainly because monitoring of its effect has been deemed unnecessary by the regulatory authorities, and hence, dose adjustment is not required. In large randomized clinical trials comparing XABANs with VKAs, XABANs have been proven to be as effective in preventing thromboembolic events as VKA [5]. Currently approved indications for XABANs are treatment and prophylaxis of venous thromboembolism (VTE) and stroke prophylaxis in patients with atrial fibrillation [6–8].
Consensus in cardiology on non-vitamin-K oral anticoagulants for patients with atrial fibrillation
Published in Current Medical Research and Opinion, 2019
Enrique Chueca Fernández, Amador López Granados, María del Pilar Zuazola Martínez, Roberto del Castillo-Medina
Until a few years ago, the only available oral anticoagulants were vitamin K antagonists (VKAs). It has been shown that these drugs reduce stroke and death by approximately 60% and 25% respectively9; however, VKAs have several disadvantages: a narrow therapeutic window, pharmacological interactions, variable metabolism and a therapeutic effect closely linked to tight control of anticoagulation levels10–12. In recent years, new oral anticoagulants, which act selectively on coagulation cascade key factors, have emerged. Three of them are direct factor Xa inhibitors (edoxaban, apixaban, rivaroxaban) and one is a direct thrombin inhibitor (dabigatran). These are known as non-vitamin-K antagonist oral anticoagulants (NOACs). These NOACs not only overcome some of the drawbacks of the VKAs, but some have also shown efficacy similar to or higher than (dabigatran high dose regimen) VKAs in stroke prevention of patients with non-valvular atrial fibrillation (NVAF), others have a lower risk of major bleeding (dabigatran in low dose regimen, edoxaban and apixaban) and all of them reduce the risk of intracranial bleeding versus VKAs2,13–17. Therefore, the latest European clinical practice guidelines recommend the preferential use of NOACs over VKAs for the majority of patients with NVAF2. Despite this evidence, NOACs are still underused. In the last cohort of the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) only 43% of patients with NVAF and at least one additional risk factor for stroke were treated with NOACs18.
Related Knowledge Centers
- Anticoagulant
- Antithrombotic
- Apixaban
- Atrial Fibrillation
- Edoxaban
- Embolism
- Venous Thrombosis
- Rivaroxaban
- Knee Replacement
- Hip Replacement