Transfer of Dabigatran and Dabigatran Etexilate Mesylate Across the Dually Perfused Human Placenta

Bapat, Priya; Kedar, Reuven; Lubetsky, Angelika; Matlow, Jeremy N.; Aleksa, Katarina; Berger, Howard; Koren, Gideon

doi:10.1097/aog.0000000000000277

Cited by 66 publications

(42 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Its prodrug has a fetal-to-maternal ratio of 0.17 after 3 hours, and dabigatran itself has a ratio of 0.33 after 3 hours; although placental viability appeared intact, the authors recommended avoiding use in pregnancy due to the potential for adverse effects on fetal blood coagulation. 60 Overall, the ACCP guidelines recommend that pregnant women avoid use of the NOACs. 41…”

Section: Non-vitamin K Oral Anticoagulantsmentioning

confidence: 99%

Diagnosis, Treatment, and Prevention of Venous Thromboembolism in Pregnancy

Marshall

2014

Postgraduate Medicine

View full text Add to dashboard Cite

Pregnancy and the puerperium put women at increased risk of venous thromboembolism (VTE) due to both baseline maternal risk factors and the development of pregnancy-related prothrombotic anatomic and physiologic changes. Pregnant women are at an approximately 5-fold increased risk of VTE compared with nonpregnant women, and the risk of VTE increases further (to ≥ 20-fold) in puerperium; risk remains increased until approximately 12 weeks postpartum. Pregnancy-related VTE accounts for about 10% of maternal deaths in the developed world. Clinicians should promptly evaluate any signs or symptoms suspicious for VTE, generally starting with ultrasound of the lower extremities. For treatment of women with established VTE, low molecular weight heparins (LMWHs) are preferred due to a favorable safety and efficacy profile. Unfractionated heparin (UFH) and potentially fondaparinux are alternatives. Warfarin should be avoided in the antepartum period due to teratogenicity, and the non-vitamin K oral anticoagulants are currently not recommended due to the lack of data. Low molecular weight heparin, UFH, and warfarin are all acceptable in the postpartum period and for breast-feeding women, but the non-vitamin K oral anticoagulants should be avoided. Prophylaxis (generally with LMWH or in some cases UFH) is recommended for women at highest risk of pregnancy-related VTE, such as those with inherited thrombophilias and a strong family or personal history of VTE. Prophylaxis with LMWH and aspirin is recommended for women with antiphospholipid syndrome. Clinicians should engage in multidisciplinary discussion, particularly around the time of delivery, to manage the details of anticoagulation in their pregnant patients.

show abstract

Section: Non-vitamin K Oral Anticoagulantsmentioning

confidence: 99%

Diagnosis, Treatment, and Prevention of Venous Thromboembolism in Pregnancy

Marshall

2014

Postgraduate Medicine

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

“…There is direct evidence of the transfer of dabigatran and its pro-drug across the term human placenta from the mother to the fetus. Therefore, its use in pregnant women is not recommended (Bapat et al, 2014).…”

Section: Characteristics In Specific Groupsmentioning

confidence: 99%

Pharmacological profile of non-vitamin K antagonist oral anticoagulants

Silva¹

2017

Afr. J. Pharm. Pharmacol.

View full text Add to dashboard Cite

female patients, oral anticoagulants are recommended, and considering shared decision between doctor and patient. However, they are contraindicated in patients with mechanical prosthetic valve and in patients with moderate-to-severe mitral stenosis and atrial fibrillation. They have also been approved for prevention and treatment of deep vein thrombosis and pulmonary embolism. Dabigatran, a direct thrombin inhibitor, was the first to be approved, followed by the factor Xa inhibitors, rivaroxaban, apixaban, and recently, in 2015, edoxaban. They have advantages such as the use of fixed-dose, with infrequent drug interaction, rapid onset of action and do not require monitoring of their anticoagulant action. Nonetheless, they have different half-lives, the need for dose adjustment according to renal function, weight and age of the patient. Its use in pregnant women and children or adolescents is not well established. There are also peculiarities about the risks of bleeding, effects on coagulation tests and specific antidotes. Through this review we discuss the pharmacokinetics and pharmacodynamics characteristics of direct oral anticoagulants, its indications, interactions and contraindications. Analysis of its efficacy, safety and risk-benefit ratio will also be addressed.

show abstract

Transfer of Dabigatran and Dabigatran Etexilate Mesylate Across the Dually Perfused Human Placenta

Cited by 66 publications

References 24 publications

Diagnosis, Treatment, and Prevention of Venous Thromboembolism in Pregnancy

Diagnosis, Treatment, and Prevention of Venous Thromboembolism in Pregnancy

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

Pharmacological profile of non-vitamin K antagonist oral anticoagulants

Contact Info

Product

Resources

About