The role of factor Xa inhibitors in venous thromboembolism treatment

Cabral, Katherine P.; Ansell, Jack

doi:10.2147/vhrm.s39726

Cited by 38 publications

(27 citation statements)

References 26 publications

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“…Targeting the point of convergence of intrinsic and extrinsic pathways enables the inhibition of thrombin production from both pathways [31,32]. Although they are an attractive alternative to warfarin, there are problems as in other therapies, in case of the non-vitamin K antagonist oral anticoagulants (including DTI and factor Xa inhibitors), difficulties may be faced when urgent reversal is needed as in case of bleeding or emergence procedure and the cost-effectiveness should also be considered [33,34].…”

Section: Resultsmentioning

confidence: 99%

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

et al. 2017

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Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents.

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Section: Resultsmentioning

confidence: 99%

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

et al. 2017

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“…Concomitant use with rifampicin leads to decrease in the plasma concentration of these drugs by 50%–54%. [29]…”

Section: Discussionmentioning

confidence: 99%

Pulmonary tuberculosis - An emerging risk factor for venous thromboembolism: A case series and review of literature

et al. 2017

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One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%–50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%–3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases.

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“…Benefits of novel direct-acting oral anticoagulants include: (a) no need to monitor INR levels, and (b) potentially decreased drug interactions and adverse events (such as bleeding episodes). One family of novel direct-acting oral anticoagulants, the direct FXaIs, such as rivaroxaban (Xarelto®) and apixaban (Eliquis®), were only made available in the USA as recently as 2010 [7]. This family of drugs all share a similar mechanism of action, inhibiting the cleavage of prothrombin into thrombin during the final step of the common coagulation cascade.…”

Section: Discussionmentioning

confidence: 99%

Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

et al. 2016

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BackgroundThe relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with factor Xa inhibitors for the treatment of pulmonary emboli have been non-inferiority studies based primarily on risk reduction (such as bleeding events), rather than resolution of specific diseases such as pulmonary embolism. Consequently, there is a lack of evidence indicating which of these agents are more effective. Here, we present a case where pulmonary emboli were treated with novel oral anticoagulants followed by warfarin to discuss the potential limitations in the use of novel oral anticoagulants as prevention or treatment of thromboembolism and the continued role for warfarin in this setting.Case presentationA 34-year-old African American woman presented to our clinic with shortness of breath and pleuritic chest pain several months post-surgery. She was identified as having multiple bilateral pulmonary embolisms and was treated with several novel oral anticoagulants, which failed to resolve the clots. Complete resolution was achieved upon switching to warfarin.ConclusionsThe patient described in this report failed to respond to novel oral anticoagulant therapy, but her emboli resolved when she was treated with warfarin. This study challenges the notion that factor Xa inhibitors are better alternatives to vitamin K anticoagulants in the treatment of pulmonary emboli based on their safety profile and ease of use alone. As a result, further post-marketing investigations into the efficacy of these agents in the management of pulmonary emboli may be warranted.

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The role of factor Xa inhibitors in venous thromboembolism treatment

Cited by 38 publications

References 26 publications

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

Pulmonary tuberculosis - An emerging risk factor for venous thromboembolism: A case series and review of literature

Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

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