PK OF LMWH AND UFH IN PREGNANCY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的总体目标是优化达替肝素和普通肝素(UFH)在妊娠期预防产科抗磷脂综合征(APS)的剂量，以降低母婴发病率/死亡率。研究人员提出的达肝素和UFH的剂量方案需要根据药代动力学和药效学参数进行验证。AUC将被用来评估怀孕前、怀孕1、2、3个月和产后的肝素暴露。在此之后，将设计一项多中心随机试验，以比较想要孩子的APS妇女的妊娠结局以及母婴并发症。本研究将涉及以下具体目标：1.进一步确定达肝素和UFH在孕前、妊娠第1、2、3个月和产后的药代动力学(浓度-时间)和药效学(浓度-效应)参数。2.根据AUC，确定与药物暴露有关的治疗反应，如活产和没有产妇或胎儿并发症。3.确定是否累积肝素剂量是毒性/并发症(即血栓栓塞事件、出血、血小板减少、骨质疏松症)的最佳预测因子。4.通过药代动力学和药效学参数，验证研究人员对达肝素和UFH在孕前、第1、2、3个月和产后的修订剂量方案。5.使用修订的剂量方案记录达肝素和UFH在妊娠期的母婴并发症。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this study is to optimize prophylactic dosing of dalteparin and unfractionated heparin (UFH) in pregnancy for women with obstetrical antiphospholipid syndrome (APS) which is used to decrease maternal and fetal morbidity/mortality. The investigators' proposed dosing protocols for dalteparin and UFH need to be verified based on pharmacokinetic and pharmacodynamic parameters. AUC will be used to estimate heparin exposure prior to pregnancy, during the 1st, 2nd, and 3rd trimesters, and postpartum. Following this, a multi-centered randomized trial will be designed to compare pregnancy outcomes, as well as maternal and fetal complications, in women with APS who are desirous of a child. The following specific objectives will be addressed in this study: 1. Further define pharmacokinetic (concentration-time) and pharmacodynamic (concentration-effect) parameters for dalteparin and UFH prior to pregnancy, during the 1st, 2nd, and 3rd trimesters and postpartum. 2. Determine therapeutic responses such as live birth and lack of maternal or fetal complications, in relation to drug exposure, based on AUC. 3. Determine if the best predictor of toxicity/complications, i.e. thromboembolic events, bleeding, thrombocytopenia, osteoporosis, is cumulative heparin dosage. 4. Verify the investigators' revised dosing protocols for dalteparin and UFH prior to pregnancy, during the 1st, 2nd, 3rd trimesters and postpartum, via pharmacokinetic and pharmacodynamic parameters. 5. Document maternal and fetal complications during pregnancy for dalteparin and UFH using the revised dosing protocols.