scholarly journals Non-VKA Oral Anticoagulants: Accurate Measurement of Plasma Drug Concentrations

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Jonathan Douxfils ◽  
Helen Mani ◽  
Valentine Minet ◽  
Bérangère Devalet ◽  
Bernard Chatelain ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Oral Anticoagulants ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Daily Practice ◽  
Drug Approval ◽  
Multiple Drug ◽  
Individual Level ◽  
Chronic Renal Impairment ◽  
Drug Concentrations

Non-VKA oral anticoagulants (NOACs) have now widely reached the lucrative market of anticoagulation. While the marketing authorization holders claimed that no routine monitoring is required and that these compounds can be given at fixed doses, several evidences arisen from the literature tend to demonstrate the opposite. New data suggests that an assessment of the response at the individual level could improve the benefit-risk ratio of at least dabigatran. Information regarding the association of rivaroxaban and apixaban exposure and the bleeding risk is available in the drug approval package on the FDA website. These reviews suggest that accumulation of these compounds increases the risk of experiencing a bleeding complication. Therefore, in certain patient populations such as patients with acute or chronic renal impairment or with multiple drug interactions, measurement of drug exposure may be useful to ensure an optimal treatment response. More specific circumstances such as patients experiencing a haemorrhagic or thromboembolic event during the treatment duration, patients who require urgent surgery or an invasive procedure, or patient with a suspected overdose could benefit from such a measurement. This paper aims at providing guidance on how to best estimate the intensity of anticoagulation using laboratory assays in daily practice.

Reversal strategies in patients treated with direct oral anticoagulants

VASA ◽  
2019 ◽  
Vol 48 (5) ◽  
pp. 389-392 ◽  
Author(s):  
Paul Gressenberger
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Study Data ◽  
Current Evidence ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Reversal Agent

Summary. Administration of direct oral anticoagulants (DOACs) for the treatment of venous thrombotic events (VTE) or non-valvular atrial fibrillation (AF) is now standard of care and has demonstrated clinical efficacy and safety in numerous clinical studies. Usually these substances have lower overall mortality and less risk of cerebral hemorrhage, but depending on the substance and study, they are more likely to cause gastrointestinal bleeding than vitamin K antagonists (VKA), the medication that used to be standard for VTE and AF. Since DOACs have very short plasma elimination half-lives compared to VKA, for most bleeding events, expert opinions suggest that withdrawal of DOACs and supportive care will likely suffice to stop a bleeding episode. Because there is a bleeding risk associated with DOACs, reversal strategies may be needed if a patient receiving DOAC therapy bleeds during surgery or an invasive procedure. So far, idarucizumab has been the only available antidote that binds specifically to dabigatran and safely and quickly reverses its anticoagulant effects. Idarucizumab has no effects on anti Xa inhibitors or other anticoagulants. To date, treatment of serious, life-threatening bleeds in patients with anti-Xa-inhibitor has involved 4 factor prothrombin complex concentrates (PCC). PCC restores normal hemostasis laboratory values in most patients with major bleeding events after anti Xa inhibitor intake. Recently, the US Food and Drug Administration (FDA) approved andexanet alfa as the first specific antidote for the anti-Xa inhibitors apixaban and rivaroxaban. So far clinical experience with this substance and data comparing it with PCC are lacking. Currently ciraparantag is under investigation as a universal reversal agent for all DOACs and low molecular weight heparin as well. Because it is so broadly applicable, ciraparantag might be a good future option for the management of most bleeding complications under anticoagulant treatment. The aim of this review is to summarize recent study data and recommendations on nonspecific and specific DOAC reversal strategies and to present the current evidence.

Dabigatran Reversal with Idarucizumab in an Emergency Lumbar Puncture: A Case Report

2019 ◽  
Vol 14 (1) ◽  
pp. 40-42 ◽  
Author(s):  
Ornella Spagnolello ◽  
Federica Letteri ◽  
Anne Falcou ◽  
Lorena Cipollone ◽  
Manuela De Michele ◽  
...  
Keyword(s):  
Lumbar Puncture ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Previous History ◽  
Antibody Fragment ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Term Treatment ◽  
Emergency Setting ◽  
Long Term Treatment

Introduction: The widespread use of direct oral anticoagulants (DOACs) has been increasing the conditions in which emergency physicians are forced to rapidly reverse anticoagulation in case of life-threatening bleeding or need of urgent surgery or invasive procedures. The recent approval of Idarucizumab, a humanized monoclonal antibody fragment (Fab), offered the opportunity to rapidly and safely neutralize the anticoagulant effect of Dabigatran. However, real-world experience of its effective use in different emergency setting is now required. Lumbar Puncture (LP) is recognized as an invasive procedure at major bleeding risk and is, therefore, contraindicated in anticoagulated patients. Conclusion: We report a successful use of Idarucizumab in an emergency LP of a young woman with a possible diagnosis of encephalitis and a previous history of venous thromboembolism on long-term treatment with Dabigatran 150 mg twice a day.

scholarly journals The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease

2020 ◽  
Author(s):  
Hyun Kuk Kim ◽  
Udaya S. Tantry ◽  
Sidney C. Smith ◽  
Myung Ho Jeong ◽  
Seung-Jung Park ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
East Asian ◽  
Bleeding Risk ◽  
Daily Practice ◽  
Position Statement ◽  
Future Directions ◽  
Asian Patients ◽  
Caucasian Patients ◽  
East Asian Patients

AbstractEast Asian patients have reduced anti-ischemic benefits and increased bleeding risk during antithrombotic therapies compared with Caucasian patients. As potent P2Y12 receptor inhibitors (e.g., ticagrelor and prasugrel) and direct oral anticoagulants are commonly used in current daily practice, the unique risk–benefit trade-off in East Asians has been a topic of emerging interest. In this article, we propose updated evidence and future directions of antithrombotic treatment in East Asian patients.

scholarly journals Management of DOAC in patients undergoing planned surgery or invasive procedure: FCSA position paper

2021 ◽  
Author(s):  
Alessandro Squizzato ◽  
Daniela Poli ◽  
Doris Barcellona ◽  
Antonia Ciampa ◽  
Elvira Grandone ◽  
...  
Keyword(s):  
Perioperative Management ◽  
Total Population ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Expert Opinions ◽  
Anticoagulated Patients

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risk. Among possible valuable answers the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: 1) multiparametric assessment of thrombotic and bleeding risk based on patients’ individual and surgical risk factor, 2) testing of prothrombin time, activated partial thromboplastin time and DOAC plasma levels before surgery or invasive procedure, 3) use of heparin, 4) restarting of full-dose of DOAC after high-risk of bleeding surgery, 5) practical non-pharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary ‘Anticoagulation Team’ with the aim to define the optimal perioperative management of anticoagulation.

Factors Influencing the Choice between DOACs and LMWHs: A Survey of German Physicians on the Treatment of Cancer-Associated Venous Thromboembolism

2020 ◽  
Vol 40 (05) ◽  
pp. 655-661
Author(s):  
Axel Matzdorff ◽  
Florian Langer
Keyword(s):  
Venous Thromboembolism ◽  
Therapeutic Option ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Daily Practice ◽  
Severe Bleeding ◽  
Oral Medications ◽  
Factors Influencing ◽  
History Of ◽  
Direct Acting

AbstractRecently direct-acting oral anticoagulants (DOACs) have become a new therapeutic option besides parenteral anticoagulants to treat cancer-associated venous thromboembolism (VTE). With this survey we wanted to identify factors influencing the choice between low-molecular-weight heparin and DOACs among physicians treating cancer patients. A questionnaire was presented at several medical educational activities on cancer care and VTE management between August 2018 and January 2019. One hundred fifteen physicians returned their surveys. The two most compelling arguments pro DOAC were when the patient had no chemotherapy and when he expressed unwillingness to apply injections. The two most important arguments against DOACs were if the patient had problems with taking oral medications or when he had a history of severe bleeding. This survey shows that future studies need to consider many more factors, particularly patient preferences and physician concerns on bleeding risk, to improve their applicability in daily practice.

Methodological Approaches to Evaluate Fetal Drug Exposure

2019 ◽  
Vol 25 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Naïm Bouazza ◽  
Frantz Foissac ◽  
Déborah Hirt ◽  
Saïk Urien ◽  
Sihem Benaboud ◽  
...  
Keyword(s):  
Cord Blood ◽  
Drug Exposure ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Fetal Drug Exposure

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

Perioperative Management of Patients Receiving New Anticoagulants

2019 ◽  
Vol 25 (19) ◽  
pp. 2149-2157 ◽  
Author(s):  
Massimo Lamperti ◽  
Andrey Khozenko ◽  
Arun Kumar
Keyword(s):  
Vitamin K ◽  
Elective Surgery ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Oral Intake ◽  
Bleeding Risk ◽  
Dietary Vitamin ◽  
Reversal Agent ◽  
Onset Of Action ◽  
Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

Perioperative Management of DOACs in Vascular Surgery: A Practical Approach

2019 ◽  
Vol 24 (38) ◽  
pp. 4518-4524 ◽  
Author(s):  
George Kouvelos ◽  
Miltiadis Matsagkas ◽  
Nikolaos Rousas ◽  
Petroula Nana ◽  
Konstantinos Mpatzalexis ◽  
...  
Keyword(s):  
Vascular Surgery ◽  
Perioperative Management ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Low Risk ◽  
Practical Approach ◽  
Current Evidence ◽  
Thromboembolic Risk ◽  
Specific Data ◽  
Vascular Procedure

Background: Approximately 10–15% of patients on DOACs have to interrupt their anticoagulant before an invasive procedure every year. The perioperative management and monitoring of DOACs have proved to be challenging, as differences in patients’ status and in the invasiveness of each procedure develop different situations that need a tailored therapeutic approach to each patient’s needs. Methods: This review aims to summarize current evidence on the perioperative management of DOACs in patients undergoing a vascular surgical procedure focusing with a practical approach on three key clinical questions: (i) can we stop DOAC therapy before the vascular procedure? (ii) is bridging therapy necessary? and (iii) which is the best perioperative strategy for interruption and resumption of the anticoagulant therapy? Results: No specific data exist for the perioperative management of vascular surgery patients on DOACs, as most studies include low number of such patients. Therapeutic strategy on how to handle DOACs perioperatively must be based on their half-life, the bleeding risk of the invasive procedures, and on the thromboembolic risk of the patient. Renal function plays a crucial role in such situations, increasing thromboembolic and bleeding risk. In general, DOACs should be stopped 2 days for high bleed risk, 1 day for low risk and should be resumed 48-72 hrs after high risk, 24 hrs after low-risk procedure. Bridging is almost never needed. Conclusion: Further perioperative research studies on patients undergoing vascular surgery are needed to confirm whether currently accepted therapeutic perioperative strategy is appropriate for these patients.

scholarly journals Left atrial appendage closure device complicated by late-onset pericardial effusion and tamponade: a case report

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Stefano Albani ◽  
Nicola Berlier ◽  
Francesco Pisano ◽  
Paolo Scacciatella
Keyword(s):  
Pericardial Effusion ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Late Onset ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Atrial Appendage ◽  
Closure Device ◽  
Device Implantation ◽  
First Case

Abstract Background Late-onset complications of left atrial appendage occlusion (LAAO) device procedure are anecdotal and there are no such complications reported in literature using Cardia Ultraseal (Cardia, Inc., Eagan, MN, USA). Case summary We report the case of a 74-year-old Caucasian man affected by paroxysmal atrial fibrillation with significant bleeding risk (familiar thrombocytopenia, macroscopic haematuria episodes during therapy with direct oral anticoagulants, HAS-BLED risk score: 4) and ischaemic risk as well (CHADSVASC score: 3). The patient was treated with LAAO device implantation for high bleeding risk. Subsequently, after 26 days from LAAO procedure, he was admitted to the emergency department for haematic cardiac tamponade. The patient was successfully treated with subxyphoidal pericardiocentesis in the acute phase, unfortunately cardiac arrest occurred during the transfer to the referral hospital for urgent cardiac surgery. Permanent neurological damage was reported and the patient died on day 28. Discussion LAAO late-onset complications are very rare and the case presented is the first case described of late-onset pericardial effusion and tamponade secondary to the Cardia Ultraseal LAAO device implantation. We present a revision of the literature regarding the occurrence of similar adverse events and discuss the hypothetical mechanism of this major complication.

scholarly journals Rivaroxaban for the treatment of cerebral venous thrombosis

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Esmaeili ◽  
Meysam Abolmaali ◽  
Sobhan Aarabi ◽  
Mohammad Reza Motamed ◽  
Samira Chaibakhsh ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Term Treatment ◽  
Background Information ◽  
Minor Bleeding ◽  
Long Term Treatment ◽  
Significant Difference

Abstract Background New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT. Materials and methods 36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects. Result Overall, 13 (36.11%) patients received Warfarin and 23 (63.89%) received Rivaroxaban. Optimal mRS score (0–1) was attained in 9 of 10 (90%) of patients treated with Rivaroxaban and 19 of 22 (86.36%) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71%) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage. Conclusion Rivaroxaban holds promise for the treatment of CVT.

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