Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting

2016 ◽  
Vol 116 (10) ◽  
pp. 651-658 ◽  
Author(s):  
Franziska Michalski ◽  
Luise Tittl ◽  
Saskia Middeldorp ◽  
Hannah Cohen ◽  
Rezan Abdul Kadir ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Pregnancy Termination ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Outcome Data ◽  
Reproductive Age ◽  
Facial Dysmorphism ◽  
Patient Counselling ◽  
In Pregnancy

SummaryToday, direct oral anticoagulants (DOAC) are widely used alternatives to Vitamin-K antagonists (VKA). Women of reproductive age may become pregnant during anticoagulation and, while VKA carry an embryotoxic potential, the risk of DOAC embryopathy is unknown. As a result, some patients elect to terminate pregnancy for fear of DOAC embryotoxicity. To assess the risk of DOAC embryopathy, we reviewed cases of DOAC exposure in pregnancy collected from physicians, literature and pharmacovigilance systems of drug authorities and manufacturers. A total of 357 reports including duplicates were available from which 233 unique cases could be identified. Information on pregnancy outcome was available in only 137/233 cases (58.8 %): 67 live births (48.9 %); 31 miscarriages (22.6 %); 39 elective pregnancy terminations (28.5 %). In 93 cases (39.9 %) no outcome data were available (including 3 cases of ongoing pregnancy). Of the 137 pregnancies with reported outcomes, seven showed abnormalities (5.1 %) of which three (2.2 %) could potentially be interpreted as embryopathy: live birth with facial dysmorphism; miscarriage in week 10 with limb abnormality; elective pregnancy termination due to a foetal cardiac defect in a woman who had to terminate a previous pregnancy due to Fallot tetralogy. Within its limitations (small numbers, incomplete outcome data) our results do not indicate that DOAC exposure in pregnancy carries a high risk of embryopathy or that DOAC exposure per se should be used to direct patient counselling towards pregnancy termination. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases indicating the strong need for a more robust system of reporting.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Applied Nanotechnologies in Anticoagulant Therapy: From Anticoagulants to Coagulation Test Performance of Drug Delivery Systems

Applied Nano ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 98-117
Author(s):  
Yuri B. G. Patriota ◽  
Luíse L. Chaves ◽  
Evren H. Gocke ◽  
Patricia Severino ◽  
Mônica F. R. Soares ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticoagulant Therapy ◽  
Test Performance ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Delivery Systems ◽  
Reversal Agent ◽  
Laboratory Assessment ◽  
Administration Routes

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor “xaban” (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.

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.

Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a “Real-world” Nationwide Registry: Insights From the FANTASIIA Study

2020 ◽  
Vol 25 (4) ◽  
pp. 316-323
Author(s):  
Martín Ruiz Ortiz ◽  
Javier Muñiz ◽  
María Asunción Esteve-Pastor ◽  
Francisco Marín ◽  
Inmaculada Roldán ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Real World ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Left Ventricular ◽  
Anticoagulant Treatment ◽  
Cancer History

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.

scholarly journals Management of thrombosis in children and neonates: practical use of anticoagulants in children

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 399-404 ◽  
Author(s):  
Paul Monagle ◽  
Fiona Newall
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Renal Vein Thrombosis ◽  
Therapeutic Agents ◽  
Vein Thrombosis ◽  
Cerebral Sinovenous Thrombosis ◽  
Sinovenous Thrombosis ◽  
American Society ◽  
Evidence Based Guidelines

Abstract Venous thrombosis (VTE) in children and neonates presents numerous management challenges. Although increasing in frequency, VTE in children and neonates is still uncommon compared with adults. The epidemiology of VTE is vastly different in neonates vs children vs adolescents vs adults. In reality, pediatric thrombosis should be viewed as a multitude of rare diseases (eg, renal vein thrombosis, spontaneous thrombosis, catheter-related thrombosis, cerebral sinovenous thrombosis), all requiring different approaches to diagnosis and with different short- and long-term consequences, but linked by the use of common therapeutic agents. Further, children have fundamentally different physiology in terms of blood flow, developmental hemostasis, and, likely, endothelial function. The American Society ofHematology 2017 Guidelines for Management of Venous Thromboembolism: Treatment of Pediatric VTE provides up-to-date evidence-based guidelines related to treatment. Therefore, this article will focus on the practical use of therapeutic agents in the management of pediatric VTE, especially unfractionated heparin, low-molecular-weight heparin, and oral vitamin K antagonists, as the most common anticoagulants used in children. Direct oral anticoagulants (DOACs) remain in clinical trials in children and should not be used outside of formal trials for the foreseeable future.

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

scholarly journals Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation

2015 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Philipp Bushoven ◽  
Sven Linzbach ◽  
Mate Vamos ◽  
Stefan H Hohnloser ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Prospective Trial ◽  
Bleeding Complications ◽  
Order Of Magnitude ◽  
Pharmacological Cardioversion

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

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