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妊娠期抗血小板及抗凝药物使用的安全性问题
Safety concerns regarding the use of antiplatelet and anticoagulant drugs during pregnancy
文章通过检索并分析近10年国内外关于妊娠期抗血小板及抗凝药物使用的指南、共识、临床研究,聚焦药物母儿安全性、不同指南推荐差异、特殊情况用药策略及管理路径,系统梳理了妊娠期抗血小板及抗凝药物的安全性证据与临床应用规范。结果提示:(1)阿司匹林是推荐用于子痫前期预防的抗血小板药物,无显著母儿风险;低分子量肝素(LMWH)因不透过胎盘、安全性高,成为妊娠期抗凝首选;普通肝素(UFH)多用于分娩前过渡,华法林及直接口服抗凝药(DOACs)因胎儿风险应用受限。(2)不同指南推荐的阿司匹林启用时间、LMWH 剂量选择,存在差异。(3)机械心脏瓣膜、遗传性易栓症等特殊情况需多学科协作制定个体化方案,遵循“个体化风险评估-药物监测-多学科协作”的管理路径。 强调妊娠期抗栓药物选择需以“母儿安全”为核心,优先选用阿司匹林及 LMWH;未来需要更多高质量研究明确 DOACs的安全性及个体化用药策略。
The article systematically reviews the safety evidence and clinical application standards of antiplatelet and anticoagulant drugs during pregnancy by retrieving and analyzing domestic and international guidelines,consensus,and clinical studies from the past decade. It focuses on maternal and fetal safety,differences in guideline recommendations,medication strategies for special cases,and management pathways. Key findings include:(1)Aspirin is the recommended antiplatelet drug for preeclampsia prevention,with no significant maternal or fetal risks. Low-molecular-weight heparin (LMWH) has become the first choice for anticoagulation during pregnancy due to its inability to cross the placenta and high safety. Unfractionated heparin (UFH) is mostly used for transition before delivery,while warfarin and direct oral anticoagulants (DOACs) are restricted due to fetal risks. (2)There are detailed differences among different guidelines regarding the initiation time of aspirin and the dosage of LMWH.(3) Special cases such as mechanical heart valves and hereditary thrombophilia,a multidisciplinary collaboration is required to develop individualized plans; additionally,a management pathway of "individualized risk assessment-drug monitoring-multidisciplinary collaboration" is proposed. The selection of antithrombotic drugs during pregnancy should take "maternal and fetal safety" as the core,and prioritize the use of aspirin and LMWH. In the future,more high-quality studies are needed to clarify the safety of DOACs and the individualized medication strategies for such drugs.
妊娠期 / 抗血小板药物 / 抗凝药物 / 安全性 / 母儿结局 / 临床指南
pregnancy / antiplatelet drugs / anticoagulant drugs / safety / maternal-fetal outcomes / clinical guidelines
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National Institute for Health and
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American College of Obstetricians and Gynecologists. ACOG Committee Opinion No.743:low-dose aspirin use during pregnancy[J]. Obstet Gynecol, 2018, 132(1):e44-e52. DOI:10.1097/AOG.0000000000002708.
Low-dose aspirin has been used during pregnancy, most commonly to prevent or delay the onset of preeclampsia. The American College of Obstetricians and Gynecologists issued the Hypertension in Pregnancy Task Force Report recommending daily low-dose aspirin beginning in the late first trimester for women with a history of early-onset preeclampsia and preterm delivery at less than 34 0/7 weeks of gestation, or for women with more than one prior pregnancy complicated by preeclampsia. The U.S. Preventive Services Task Force published a similar guideline, although the list of indications for low-dose aspirin use was more expansive. Daily low-dose aspirin use in pregnancy is considered safe and is associated with a low likelihood of serious maternal, or fetal complications, or both, related to use. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the U.S. Preventive Services Task Force guideline criteria for prevention of preeclampsia. Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery. Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia. Women at risk of preeclampsia are defined based on the presence of one or more high-risk factors (history of preeclampsia, multifetal gestation, renal disease, autoimmune disease, type 1 or type 2 diabetes, and chronic hypertension) or more than one of several moderate-risk factors (first pregnancy, maternal age of 35 years or older, a body mass index greater than 30, family history of preeclampsia, sociodemographic characteristics, and personal history factors). In the absence of high risk factors for preeclampsia, current evidence does not support the use of prophylactic low-dose aspirin for the prevention of early pregnancy loss, fetal growth restriction, stillbirth, or preterm birth.
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US Preventive Services Task Force,
Preeclampsia is one of the most serious health problems that affect pregnant persons. It is a complication in approximately 4% of pregnancies in the US and contributes to both maternal and infant morbidity and mortality. Preeclampsia also accounts for 6% of preterm births and 19% of medically indicated preterm births in the US. There are racial and ethnic disparities in the prevalence of and mortality from preeclampsia. Non-Hispanic Black women are at greater risk for developing preeclampsia than other women and experience higher rates of maternal and infant morbidity and perinatal mortality.To update its 2014 recommendation, the USPSTF commissioned a systematic review to evaluate the effectiveness of low-dose aspirin use to prevent preeclampsia.Pregnant persons at high risk for preeclampsia who have no prior adverse effects with or contraindications to low-dose aspirin.The USPSTF concludes with moderate certainty that there is a substantial net benefit of daily low-dose aspirin use to reduce the risk for preeclampsia, preterm birth, small for gestational age/intrauterine growth restriction, and perinatal mortality in pregnant persons at high risk for preeclampsia.The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia. (B recommendation).
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Women who are pregnant or in the postpartum period have a fourfold to fivefold increased risk of thromboembolism compared with nonpregnant women (1, 2). Approximately 80% of thromboembolic events in pregnancy are venous (3), with a prevalence of 0.5–2.0 per 1,000 pregnant women (4–9). Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the United States, accounting for 9.3% of all maternal deaths (10).
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In July 2022, these guidelines were reviewed by an expert work group convened by ASH. Review included limited searches for new evidence and discussion of the search results. Following this review, the ASH Committee on Quality agreed to continue monitoring the supporting evidence rather than revise or retire these guidelines at this time. Limited searches and expert review will be repeated annually going forward until these guidelines are revised or retired.
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Venous thromboembolism is recognized as a leading cause of maternal death in the United States. Thromboprophylaxis has been highlighted as a key preventive measure to reduce venous thromboembolism-related maternal deaths. However, the expanded use of thromboprophylaxis in obstetrics will have a major impact on the use and timing of neuraxial analgesia and anesthesia for women undergoing vaginal or cesarean delivery and other obstetric surgeries. Experts from the Society of Obstetric Anesthesia and Perinatology, the American Society of Regional Anesthesia, and hematology have collaborated to develop this comprehensive, pregnancy-specific consensus statement on neuraxial procedures in obstetric patients receiving thromboprophylaxis or higher dose anticoagulants. To date, none of the existing anesthesia societies' recommendations have weighed the potential risks of neuraxial procedures in the presence of thromboprophylaxis, with the competing risks of general anesthesia with a potentially difficult airway, or maternal or fetal harm from avoidance or delayed neuraxial anesthesia. Furthermore, existing guidelines have not integrated the pharmacokinetics and pharmacodynamics of anticoagulants in the obstetric population. The goal of this consensus statement is to provide a practical guide of how to appropriately identify, prepare, and manage pregnant women receiving thromboprophylaxis or higher dose anticoagulants during the ante-, intra-, and postpartum periods. The tactics to facilitate multidisciplinary communication, evidence-based pharmacokinetic and spinal epidural hematoma data, and Decision Aids should help inform risk-benefit discussions with patients and facilitate shared decision making.
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利益冲突 所有作者均声明不存在利益冲突
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