scholarly journals The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Prudhvi Battula ◽  
Jose Otero ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemoglobin Concentration ◽  
Thrombin Inhibitor ◽  
Free Hemoglobin ◽  
Intracranial Hemorrhages ◽  
The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

scholarly journals Using direct oral anticoagulants (DOACs) in cancer and other high-risk populations

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Nick van Es ◽  
Harry R. Büller
Keyword(s):  
High Risk ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
Efficacy And Safety ◽  
Practical Advantage ◽  
High Risk Populations

Abstract The major practical advantage of the direct oral anticoagulants (DOACs), comprising the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, over vitamin K antagonists is their fixed dosing without the need for laboratory monitoring. With the recent, rapid introduction of the DOACs for the treatment of acute venous thromboembolism (VTE), clinicians are now faced with various questions regarding the efficacy and safety of these compounds overall and in specific high-risk populations. The collective evidence from 6 large clinical trials involving 27,000 patients has demonstrated that DOACs are as effective as vitamin K antagonists (VKA) in preventing recurrent VTE while being associated with a significantly lower risk of major bleeding. These findings are consistent in subgroups of patients with pulmonary embolism, the elderly, and those patients with a high body weight or moderate renal insufficiency, making these agents suitable for a broad spectrum of patients with VTE. DOACs are also an attractive treatment option in patients with VTE and concomitant cancer, thrombotic antiphospholipid syndrome, or heparin-induced thrombocytopenia, but the currently available clinical data is insufficient to make evidence-based recommendations on the use of DOACs in these settings. Several studies evaluating the efficacy and safety of DOACs in these high-risk populations are underway.

scholarly journals Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Ali Zalpour ◽  
Thein Hlaing Oo
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Current Evidence ◽  
Thrombin Inhibitor ◽  
Prevention And Treatment ◽  
Financial Impacts

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation: Update and Periprocedural Management

2019 ◽  
Vol 39 (2) ◽  
pp. 54-67 ◽  
Author(s):  
Joya D. Pickett
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Fixed Dose ◽  
Thrombin Inhibitor ◽  
National Guidelines ◽  
Nonvalvular Atrial Fibrillation ◽  
Periprocedural Management

Vitamin K antagonists (eg, warfarin) have been the standard of care for stroke prophylaxis in atrial fibrillation. The direct oral anticoagulants dabigatran (direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (direct factor Xa inhibitors) are as efficacious as and in some instances superior to vitamin K antagonists in the prevention of stroke, systemic embolism, and major bleeding compared with warfarin for nonvalvular atrial fibrillation. Benefits of direct oral anticoagulants include a rapid onset of therapeutic effect, fixed dose-response relationships without the need for routine monitoring, a short half-life, and infrequent need for periprocedural bridging with a parenteral agent. However, direct oral anticoagulants differ in subsets of patients. Critical care and advanced practice nurses must understand these differences, prescribing considerations, drug aherence interventions, drug-drug interactions, and periprocedural management. This article presents an update and review of direct oral antigcoagulants based on the latest national guidelines.

scholarly journals Pharmacogenetics of Direct Oral Anticoagulants

2021 ◽  
Author(s):  
Natalia Shnayder ◽  
Marina Petrova ◽  
Elena Bochanova ◽  
Olga Zimnitskaya ◽  
Alina Savinova ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Pharmacokinetic Profile ◽  
Thrombin Inhibitor ◽  
Oral Vitamin ◽  
Treatment And Prevention ◽  
Venous Thromboembolic ◽  
The Individual

For more than 50 years, oral vitamin K antagonists were the choice of anticoagulant for the long-term treatment and prevention of arterial and venous thromboembolic events. In recent years, four direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban have been compared with warfarin for thromboembolism prevention. These anticoagulants directly inhibit specific proteins within the coagulation cascade; in contrast, oral vitamin K antagonists inhibit the synthesis of vitamin K-dependent clotting factors. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban and edoxaban, the factor Xa inhibitors, produce a more predictable, less labile anticoagulant effect. DOACs do not have limitations inherent vitamin K antagonists. DOACs have a predictable pharmacokinetic profile and are free of advers drugs reactions inherent in vitamin K antagonists. However, it is necessary to take into account the pharmacogenetic characteristics of the individual that can affect effectiveness and safety of use of DOACs. The results carried out to the present fundamental and clinical studies of DOACs studies demonstrate an undeniable the influence of genome changes on the pharmacokinetics and pharmacodynamics of DOACs. However, the studies need to be continued. There is a need to plan and conduct larger studies in various ethnic groups with the inclusion of sufficient associative genetic studies of the number of patients in each of the documented groups treatments with well-defined phenotypes.

scholarly journals Advantages and disadvantages of direct oral anticoagulants in older patients

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Antonio Cherubini ◽  
Barbara Carrieri ◽  
Paolo Marinelli
Keyword(s):  
Older Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitor ◽  
Vein Thrombosis ◽  
Advantages And Disadvantages ◽  
Gray Areas ◽  
Deep Vein

Atrial fibrillation (AF) and venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, are conditions that increase with age. Anticoagulant therapy is strongly recommended both in patients with AF for the prevention of cardioembolic stroke, and for treatment of VTE and prevention of recurrent VTE. Until recently, vitamin K antagonists (VKAs) were the only oral drugs for long-term anticoagulation. In the past decade, four direct oral anticoagulants (DOACs) were approved: a direct thrombin inhibitor (dabigatran) and three factor Xa inhibitors (apixaban, rivaroxaban, edoxaban). Despite increasing evidence demonstrating the efficacy and safety of DOACs in older patients, there are still gray areas where the use of VKAs might be valuable.

scholarly journals Factor XI as a Target for New Anticoagulants

2021 ◽  
Vol 41 (02) ◽  
pp. 104-110
Author(s):  
James C. Fredenburgh ◽  
Jeffrey I. Weitz
Keyword(s):  
Vitamin K ◽  
Animal Studies ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Clotting Factors ◽  
Factor Xi ◽  
Factor Xi Deficiency

AbstractDespite advances in anticoagulant therapy, thrombosis remains the leading cause of morbidity and mortality worldwide. Heparin and vitamin K antagonists (VKAs), the first anticoagulants to be used successfully for the prevention and treatment of thrombosis, are associated with a risk of bleeding. These agents target multiple coagulation factors. Thus, by activating antithrombin, heparin mainly inhibits factor Xa and thrombin, whereas VKAs lower the levels of the vitamin K–dependent clotting factors. Direct oral anticoagulants, which have replaced VKAs for many indications, inhibit only factor Xa or thrombin. Although the direct oral anticoagulants are associated with less bleeding than VKAs, bleeding remains their major side effect. Epidemiological and animal studies have identified factor XI as a target for potentially safer anticoagulant drugs because factor XI deficiency or inhibition protects against thrombosis and is associated with little or no bleeding. Several factor XI–directed strategies are currently under investigation. This article (1) reviews the rationale for the development of factor XI inhibitors, (2) identifies the agents in most advanced stages of development, (3) describes the results of completed clinical trials and provides a summary of those underway, and (4) highlights the opportunities and challenges for this next generation of anticoagulants.

Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

1979 ◽  
Vol 42 (04) ◽  
pp. 1296-1305 ◽  
Author(s):  
R M Bertina ◽  
W van der Marel-van Nieuwkoop ◽  
E A Loeliger
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Factor V ◽  
Anticoagulant Treatment ◽  
Factor Ii ◽  
K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

scholarly journals Falls in ED patients: do elderly patients on direct oral anticoagulants bleed less than those on vitamin K antagonists?

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Martin Müller ◽  
Ioannis Chanias ◽  
Michael Nagler ◽  
Aristomenis K. Exadaktylos ◽  
Thomas C. Sauter
Keyword(s):  
Elderly Patients ◽  
Vitamin K ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Lower Odds ◽  
Anticoagulated Patients ◽  
Proportional Incidence

Abstract Background Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA). Methods Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes. Results In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes. Conclusions Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.

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