Rivaroxaban transfer across the dually perfused isolated human placental cotyledon

Bapat, Priya; Pinto, Leonardo; Lubetsky, Angelika; Berger, Howard; Koren, Gideon

doi:10.1016/j.ajog.2015.06.065

Cited by 52 publications

(36 citation statements)

References 26 publications

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“…These agents are likely to cross the placenta and their human reproductive risks are unknown. 161,162 Although there are no studies comparing different anticoagulation regimens in pregnant patients with CVT, prior systematic reviews suggest that the incidence of bleeding in pregnant women receiving LMWH is low for antepartum haemorrhage (0.43%, 95% CI 0.22-0.75%), postpartum haemorrhage (0.94%, 95%CI 0.36-0.98%) and wound haematoma (0.61%, 95% CI 0.36-0.98%). 163 With respect to foetal safety (teratogenicity, congenital malformations, foetal bleeding) there is ample experience with UFH and LMWH in pregnant women.…”

mentioning

confidence: 99%

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – Endorsed by the European Academy of Neurology

Ferro

Bousser

Canhão

et al. 2017

European Stroke Journal

154

103

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The current proposal for cerebral venous thrombosis guideline followed the Grading of Recommendations, Assessment, Development, and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews of all available evidence and writing recommendations and deciding on their strength on an explicit and transparent manner, based on the quality of available scientific evidence. The guideline addresses both diagnostic and therapeutic topics. We suggest using magnetic resonance or computed tomography angiography for confirming the diagnosis of cerebral venous thrombosis and not screening patients with cerebral venous thrombosis routinely for thrombophilia or cancer. We recommend parenteral anticoagulation in acute cerebral venous thrombosis and decompressive surgery to prevent death due to brain herniation. We suggest to use preferentially low-molecular weight heparin in the acute phase and not using direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations due to very poor quality of evidence concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that in women who suffered a previous cerebral venous thrombosis, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular weight heparin should be considered throughout pregnancy and puerperium. Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of cerebral venous thrombosis. KeywordsCerebral venous thrombosis, dural sinus thrombosis, Grading of Recommendations, Assessment, Development, and Evaluation, angiography, venography, D dimers, prothrombotic screening, cancer screening, anticoagulation, heparin, thrombolysis, thrombectomy, acetazolamide, steroids, decompressive surgery, hemicraniectomy, lumbar puncture, shunt, pregnancy, puerperium, contraception, antiepileptic drugs These guidelines followed the traditional methodology of combining review of scientific evidence with expert opinion and classifying evidence and recommendations in complex grading systems, using a matrix combining classes of recommendations with levels of evidence.Since 2010-2011 new information has accumulated on multiple aspects of the diagnosis and management of CVT. We aim to update previous EFNS guidelines using a clearer and evidence base methodology. To achieve that aim, the current proposal for CVT guidelines followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system, 3 formulating relevant diagnostic and treatment questions, performing systematic reviews of all available eviden...

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mentioning

confidence: 99%

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – Endorsed by the European Academy of Neurology

Ferro

Bousser

Canhão

et al. 2017

European Stroke Journal

154

103

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“…The MWs of apixaban edoxaban and rivaroxaban are 460, 548, and 436 Da, respectively [http://pubchem.ncbi.nlm.nih.gov]. As may be anticipated with these MWs and as detailed here, animal and in vitro studies in a human placental perfusion model indicate that apixaban, dabigatran, and rivaroxaban, respectively, exhibit placental transfer.…”

Section: General Considerations Regarding Maternofetal Transfer Of Doacsmentioning

confidence: 74%

“…Apixaban exhibited extensive lacteal excretion, representing greater than 96% of sample radioactivity, with the high milk-to-maternal plasma ratio possibly due to active transport into breast milk [2]. In a human placental perfusion model, unbound rivaroxaban was found to cross term placenta rapidly with a similar maternal-to-fetal and fetal-to-maternal ratio of 0.69 (n = 5 and 2, respectively) after 3 h [17].…”

Section: Animal and In Vitro Studies On Doacs During Pregnancy And Lamentioning

confidence: 99%

Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH

Cohen

Arachchillage

Middeldorp

et al. 2016

Journal of Thrombosis and Haemostasis

114

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“…The authors acknowledge some of the limitations of this model: only full-term placentae were used (so the results cannot be extrapolated to earlier gestational ages when placental structure is different), and non-placental PK factors (such as protein binding and clearance rate) were not accounted for. Rivaroxaban is highly protein-bound (to serum albumin in the maternal circulation) and, as such, the fetal exposure to rivaroxaban is predicted to be less than that shown in this perfusion model (Bapat et al, 2015). It is likely, therefore, that rivaroxaban enters the fetal circulation but whether in significant amounts or if sufficient to negatively affect the developing human embryo or fetus remains unclear.…”

Section: Pregnancymentioning

confidence: 81%

Current challenges and future prospects in oral anticoagulant therapy

2017

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The choice for oral anticoagulant (OAC) therapy was previously limited to the vitamin K antagonists (VKAs). The advent of the direct oral anticoagulants (DOACs) brought with it the expectation that oral anticoagulation would become simpler (with the elimination of routine monitoring and introduction of a fixed-dose anticoagulant), and that the use of VKAs would be slowly phased out. Although DOACs have made anticoagulation more convenient and accessible, we are now faced with what can be described as a tyranny of choice, together with many unanswered questions relating to DOAC use. These include optimal DOAC selection and dosing, use in complex 'real-world' patients, the role for monitoring and issues surrounding adherence. Warfarin remains the anticoagulant of choice in certain scenarios (e.g. metallic heart valves). The future holds much excitement: clinical studies are underway to expand the indications for DOACs and experience continues to grow outside the trials setting.

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Rivaroxaban transfer across the dually perfused isolated human placental cotyledon

Cited by 52 publications

References 26 publications

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – Endorsed by the European Academy of Neurology

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – Endorsed by the European Academy of Neurology

Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH

Current challenges and future prospects in oral anticoagulant therapy

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