scholarly journals A systematic review on the use of new anticoagulants in pregnancy

2013 ◽  
Vol 6 (2) ◽  
pp. 64-71 ◽  
Author(s):  
Ai-Wei Tang ◽  
Ian Greer
Keyword(s):  
Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Cochrane Library ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Adverse Pregnancy ◽  
Newer Anticoagulants ◽  
The Cochrane Library ◽  
In Pregnancy

New anticoagulants such as direct factor Xa inhibitors and direct thrombin inhibitors have been recently developed, but their experience in pregnancy is limited. This review therefore aims to systematically search for studies on the use of these newer anticoagulants in pregnancy and the puerperal period. Searches were performed on electronic databases MEDLINE (from 1966), EMBASE (from 1974) and the Cochrane Library, until October 2011 using terms of ‘pregnancy’, ‘puerperium’, ‘breastfeeding’ and names of specific anticoagulants. The search yielded 561 citations and 11 studies (10 on fondaparinux, 1 on ximelagatran) were included. Newer anticoagulants (fondaparinux, hirudin and argatroban) on the limited evidence appear not to have adverse pregnancy outcomes, but there is currently no experience of new oral anticoagulants (rivaroxaban, apixaban, betrixaban or dabigatran) use in pregnancy. There is a need for reporting on new oral anticoagulation use in pregnancy to provide more information about the safety and risks to the fetus in utero.

Old and new anticoagulants

2011 ◽  
Vol 31 (01) ◽  
pp. 21-27 ◽  
Author(s):  
U. Harbrecht
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Clotting Factor ◽  
Direct Thrombin Inhibitors ◽  
Self Monitoring ◽  
New Anticoagulants ◽  
Gastrointestinal Side Effects

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

Spotlight on real-world evidence for the treatment of DVT: XALIA

2016 ◽  
Vol 116 (S 02) ◽  
pp. S41-S49 ◽  
Author(s):  
Alexander Turpie ◽  
Walter Ageno
Keyword(s):  
Venous Thromboembolism ◽  
Real World ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Standard Of Care ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Real World Evidence ◽  
Recurrent Vte

SummaryVenous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs). The direct, oral factor Xa inhibitor rivaroxaban was the first to be approved for treatment of acute DVT and PE and secondary prevention of recurrent VTE events based on data from EINSTEIN DVT and EINSTEIN PE, respectively. Real-world evidence now helps to further support data from RCTs, and also bridges the gap for physicians regarding any areas of clinical uncertainty that may not be addressed by RCTs. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was the first large, prospective, observational, real-world study that has investigated the safety and effectiveness profile of rivaroxaban in patients with DVT and PE associated with DVT in routine clinical practice. This article will present the key clinical outcomes from this important global non-interventional study, and will discuss remaining questions to be addressed in Phase IV studies.

scholarly journals New anticoagulants for the treatment of venous thromboembolism

2016 ◽  
Vol 42 (2) ◽  
pp. 146-154 ◽  
Author(s):  
Caio Julio Cesar dos Santos Fernandes ◽  
José Leonidas Alves Júnior ◽  
Francisca Gavilanes ◽  
Luis Felipe Prada ◽  
Luciana Kato Morinaga ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
New Anticoagulants ◽  
Acute Pulmonary Thromboembolism ◽  
Deep Vein

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

New anticoagulants for secondary haemostasis

2009 ◽  
Vol 29 (03) ◽  
pp. 256-259 ◽  
Author(s):  
G. Nowak
Keyword(s):  
Blood Coagulation ◽  
Oral Anticoagulants ◽  
Individual Case ◽  
The Body ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Narrow Therapeutic Range ◽  
The Individual

SummaryIn contrast to heparins and oral anticoagulants, anti IIa inhibitors (thrombin inhibitors) are able to directly inhibit the protease activity of thrombin and can thereby precisely control the blood coagulation process.Direct thrombin inhibitors are either biosimilars (r-hirudin) or synthetically produced substances (bivalirudin, argatroban, dabigatran). In 1997 r-hirudin was introduced into clinical practice, however due to its narrow therapeutic range and the necessity of drug monitoring it has not gained widespread clinical use by now. Since 2004 and 2005 the synthetic thrombin inhibitors bivalirudin and argatroban, respectively, are available. With dabigatran the first oral synthetic thrombin inhibitor followed in 2008. These four drugs can inhibit even clot bound thrombin and show low plasma protein binding. They differ in respect to route and duration of application as well as elimination from the body, thereby offering a precise inhibition of blood coagulation adjusted to the individual case and without danger of HIT II. These advantages shall be used and advanced by the development of further direct thrombin inhibitors.

Ximelagatran: A new type of oral anticoagulant

2005 ◽  
Vol 21 (4) ◽  
pp. 480-486
Author(s):  
Lisa Kwok ◽  
Dana Molckovsky ◽  
Michel Boucher
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Web Sites ◽  
Liver Toxicity ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Thrombin Inhibitors ◽  
Cochrane Library ◽  
Direct Thrombin Inhibitors ◽  
Elevated Liver Enzymes

Objectives: This assessment sought to evaluate the comparative benefit and adverse effect profile of ximelagatran, as well as the clinical issues surrounding its potential use.Methods: We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information.Results: Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants.Conclusions: Given its apparent simplicity of use, ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.

scholarly journals Direct oral anticoagulant (DOAC) interference in hemostasis assays

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 129-133
Author(s):  
Karen A. Moser ◽  
Kristi J. Smock
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Sample Collection ◽  
Educational Materials ◽  
Direct Factor Xa Inhibitors ◽  
Testing Algorithms

Abstract Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results. Preanalytic strategies to avoid DOAC interference include selecting alternatives to clot-based hemostasis assays in patients taking DOACs when possible and sample collection timed when the patient is off anticoagulant therapy or at the expected drug trough. Clinical laboratories may also provide educational materials that clearly describe possible interferences from DOAC, develop testing algorithms to aid in detection of DOAC in submitted samples, use DOAC-neutralizing agents to remove DOACs before continuing with testing, and write interpretive comments that explain the effects of DOAC interference in hemostasis tests. Using a combination of the described strategies will aid physicians and laboratorians in correctly interpreting hemostasis and thrombosis laboratory tests in the presence of DOACs.

Controversies of Anticoagulation Reversal in Life-Threatening Bleeds

2010 ◽  
Vol 23 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Stephen Rolfe ◽  
Stella Papadopoulos ◽  
Katherine P. Cabral
Keyword(s):  
Factor Viia ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
New Anticoagulants ◽  
Anticoagulant Reversal ◽  
Life Threatening ◽  
Minimize Blood Loss ◽  
Warfarin Reversal ◽  
Optimal Approach ◽  
Newer Anticoagulants

Therapeutic anticoagulation with heparins, warfarin, and anti-Xa inhibitors carry an inherent risk of complications due to their multifaceted pharmacokinetic and pharmacodynamic properties as well as narrow therapeutic ranges. When an anticoagulated patient presents with a major or life-threatening bleed, immediate and effective therapy may be necessary to reverse the effects of the anticoagulant, minimize blood loss, and reduce patient morbidity and mortality. Optimal agents and strategies for anticoagulant reversal are limited, particularly for newer anticoagulants. The literature describing such strategies available to reverse the effects of anticoagulants in the setting of a bleed is limited, and therefore many controversies exist. Thus, as new anticoagulants become available, without a specific agent for reversal, the concerns and controversies related to this topic must be addressed. The purpose of this review is to discuss the management of major or life-threatening bleeds by addressing the following controversies: (1) the use of recombinant factor VIIa for rapid reversal of warfarin in patients with intracerebral hemorrhage, (2) the role of prothrombin complex concentrate in emergent warfarin reversal, and (3) the optimal approach to reverse newer anticoagulants such as low molecular weight heparins, fondaparinux, and direct thrombin inhibitors.

New Anticoagulants

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 450-456 ◽  
Author(s):  
Kenneth A. Bauer
Keyword(s):  
Factor Xa ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Percutaneous Coronary Interventions ◽  
New Anticoagulants ◽  
Fda Approval ◽  
Percutaneous Coronary ◽  
Prevention And Treatment

Abstract Traditional anticoagulant drugs, including unfractionated heparin and warfarin, have several limitations. New anticoagulants have been developed that target a single coagulation factor and have predictable dose-response relationships. These include direct thrombin inhibitors and factor Xa inhibitors. Two parenteral direct thrombin inhibitors, lepirudin and argatroban, have FDA approval for the management of heparin-induced thrombocytopenia (HIT). Bivalirudin is a parenteral direct thrombin inhibitor that is licensed for patients undergoing percutaneous coronary interventions and for those with HIT who require percutaneous coronary interventions. Ximelagatran, an oral prodrug of the direct thrombin inhibitor melagatran, showed efficacy in the prevention and treatment of venous thromboembolism as well as stroke prevention in patients with atrial fibrillation. However, due to nonhematologic safety concerns, it did not receive FDA approval in the US. Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly selectively inhibiting factor Xa. Fondaparinux demonstrated efficacy compared to low-molecular-weight heparin in randomized clinical trials and is FDA approved for the prevention and treatment of venous thromboembolism. The OASIS 5 trial in non-ST-segment elevation acute coronary syndromes recently demonstrated that the fondaparinux dose approved for prophylaxis of deep venous thrombosis is as efficacious with respect to ischemic outcomes as therapeutic doses of enoxaparin; fondaparinux, however, was associated with a substantial reduction in major bleeding at 9 days and mortality at 1 and 6 months. A number of oral direct factor Xa inhibitors as well as other oral direct thrombin inhibitors are in clinical development for the prevention and treatment of thrombosis; the current status of these anticoagulants is reviewed along with the challenges faced in designing pivotal clinical trials of these agents in comparison to existing anticoagulants.

scholarly journals Atrial Fibrillation: A Review of Recent Studies with a Focus on Those from the Duke Clinical Research Institute

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Meena P. Rao ◽  
Sean D. Pokorney ◽  
Christopher B. Granger
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
The United States ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Number Of Patients ◽  
Worse Prognosis ◽  
Research Institute

Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute.

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