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Study Question: What evaluation and care is offered to women after unexplained recurrent pregnancy loss (RPL) or intra-uterine foetal death (IUFD) and what are the reproductive outcomes?, Summary Answer: Women are assessed for thrombophilia and often treated with low-molecular weight heparin (LMWH) and/or low-dose aspirin (ASA)., What Is Known Already: Randomized controlled trials (RCTs) on possible efficacy of heparins and/or aspirin have been inconclusive due to limited power to detect a difference and patient heterogeneity., Study Design, Size, Duration: Prospective multicentre cohort study performed in 12 hospitals in three countries between 2012 and 2019., Participants/materials, Setting, Methods: All consecutive pregnant women with recurrent PL (≥3 losses or 2 losses in the presence of at least one euploid foetal karyotype) or at least one IUFD. Eligible women may have undergone thrombophilia testing before conception, at the discretion of local providers. The possible assignment of women to treatments (such as LMWH) was not decided a priori but was determined based on the responsible provider's current practice. Aims of the study were: (i) to evaluate factors associated with pregnancy outcome; (ii) to compare clinical management strategies in women with and without a subsequent successful pregnancy; and (iii) to evaluate characteristics of women who may benefit from antithrombotic therapy. A propensity score matching method was used to balance the differences in baseline characteristics., Main Results and the Role of Chance: A matched sample of 265 pregnant women was analysed, with all undergoing thrombophilia screening; 103 out of 119 (86.6%) with and 98/146 (67.1%) without thrombophilia were prescribed with LMWH and/or ASA. Overall, live-births were recorded in 204 cases (77%), PL or IUFD in 61 (23%) pregnancies. Logistic regression showed a significant interaction between thrombophilia and treatment with LMWH (P = 0.03). Findings from sensitivity analysis showed odds ratio (OR) for pregnancy loss in women with inherited or acquired thrombophilia in absence of any treatment was 2.9 (95% CI, 1.4-6.1); the administration of LMWH (with or without ASA) was associated with higher odds of live-birth (OR, 10.6; 95% CI, 5.0-22.3). Furthermore, in women without thrombophilia, the odds of live-birth was significantly and independently associated with LMWH prophylaxis (alone or in association with ASA) (OR, 3.6; 95% CI, 1.7-7.9)., Limitations, Reasons for Caution: While the propensity score matching allows us to balance the differences in baseline characteristics, it does not eliminate all confounding., Wider Implications of the Findings: Antithrombotic prophylaxis during pregnancy may be effective in women with otherwise unexplained PL or IUFD, and even more useful in those with thrombophilia., Study Funding/competing Interest(s): The study was funded by Italian Ministry of Health (Ricerca Corrente 2018-2020). Dr G.P. has received research grant support from Bristol Myers Squibb/Pfizer Alliance, Janssen, Boston Scientific Corporation, Bayer, and Portola and consultant fees from Amgen and Agile Therapeutics. Dr E.G. has received consultant fees from Italfarmaco and Sanofi. All other authors declare that they have no conflict of interest., Trial Registration Number: NCT02385461., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Direct-acting antiviral drugs (DAAs) were recently approved for treating hepatitis C virus-related chronic hepatitis. As advanced chronic liver disease may predispose patients to thrombotic events, it is still uncertain whether DAAs may influence the actual risk of major arterial and venous thrombotic events. We performed a systematic review to assess the incidence of major vascular events in patients receiving DAAs for HCV chronic hepatitis during phase-III randomized controlled trials (RCTs). Two reviewers identified studies through Pubmed database until October 2015. Reporting and incidence of any vascular events were compared with reporting and incidence of major bleeding, anemia (a prespecified safety outcome) and headache (a common non-prespecified safety outcome). 33 RCTs, encompassing 14,764 patients, were included. Only 13 (39%) and 4 (12%) RCTs provide data on any arterial or venous events, respectively. Occurrence of anemia and headache is reported in all studies. Crude unweighted rate of major arterial events is 0.16% (95% CI 0.10-0.24) of the total included population and 0.47% in those 13 RCTs reporting data. Crude unweighted rate of major venous events is 0.03% of the total included population (95% CI 0.01-0.08) and 0.22% in those four RCTs reporting data. Crude unweighted rate of major bleeding is 0.07% (95% CI 0.03-0.1). Incidence of thrombotic events in HCV patients receiving DAAs may be low, but an incorrect estimation cannot be excluded.

: Atrial fibrillation is the most common arrhythmia in over-midlife patients. In addition to systolic heart failure, cerebral thromboembolism represents the most dramatic complication of this rhythm disorder, contributing to morbidity and mortality. Traditionally, anticoagulation has been considered the main strategy in preventing stroke and systemic embolism in atrial fibrillation patients and vitamin K-dependent antagonists have been widely used in clinical practice. Recently, the development of direct oral anticoagulants has certainly improved the management of this disease, providing, for the first time, the opportunity to go beyond vitamin K-dependent antagonists limits. In the RE-LY trial, dabigatran 150 mg twice daily was superior to warfarin in the prevention of stroke or systemic embolism and dabigatran 110 mg twice daily was noninferior. Both doses greatly reduced hemorrhagic stroke, and dabigatran 110 mg twice daily significantly reduced major bleeding compared with warfarin. Based on these results, dabigatran, a direct thrombin inhibitor, was the first direct oral anticoagulant to receive the regulatory approval for nonvalvular atrial fibrillation patients. To date, a specific reversal agent has just been approved as an antidote for this molecule. This review provides a summary of randomized trials, postmarket registries and specific clinical-settings summary on dabigatran in nonvalvular atrial fibrillation.

Introduction: Dual antiplatelet therapy is the standard of care for patients with acute coronary syndromes or with recent coronary stents implantation. P2Y12 receptor antagonists have shown to reduce the risk of recurrent ischemic events among these patients, at the expense of an increased risk of bleeding. Cangrelor is a novel, intravenous, short-acting, reversible platelet P2Y12 inhibitor, which has been evaluated for the treatment of arterial thrombosis., Areas Covered: Studies on the pharmacological characteristics of cangrelor and clinical trials were retrieved by a PubMed literature search., Expert Opinion: Cangrelor has been tested in patients with coronary artery diseases undergoing percutaneous coronary intervention and as bridging therapy for patients undergoing coronary artery bypass graft. The rapid peak of action allows a fast and complete inhibition of platelet aggregation; the rapid offset is advantageous in case of bleeding complications; and finally, the intravenous administration also makes this drug suitable for patients unable to consume oral medications. Unfortunately, the large clinical trials evaluating cangrelor in percutaneous coronary intervention did not show superiority to the standard antiplatelet therapy, and its future use in this setting still needs to be better assessed. Conversely, when used as bridging therapy to coronary artery bypass graft, cangrelor showed promising results.