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Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice

机译:血管损伤,妊娠和促血管免疫球蛋白给药在小鼠中的组合血栓形成作用

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Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown. Late pregnant (gestation days 17–20) or early lactation (days 1–3) and control female mice were treated with IGs supplemented with human FXIa then subjected to ferric chloride (FeCl3) vessel injury. Occlusion of blood vessel was assessed by recording blood velocity in the femoral vein for 20?min using doppler ultrasound laser imaging. FXIa dose was selected by the ability to increase thrombin generation in mouse plasma in vitro. FXIa produced robust thrombin generation in mouse plasma ex vivo. Following FeCl3 injury, pregnant and non-pregnant mice receiving IG?+?FXIa exhibited faster reduction of blood velocity in femoral vein compared to IG alone or untreated controls. In vitro, thrombin generation in plasma samples collected after thrombosis in FXIa-treated animals was elevated and could be reduced by anti-FXI antibody. Our results suggest that intravenously-administered FXIa may contribute to thrombosis at the site of vascular injury in both pregnant and non-pregnant animals.
机译:孕妇患血栓性不良事件的风险增加。血浆衍生的免疫球蛋白(Ig)产品用于各种适应症的妊娠中,可含有促血管杂质活化凝血因子XI(FXIA)。促凝血剂Ig产品已与增加的血栓形成性有关,但它们在妊娠中的作用是未知的。怀孕(妊娠日17-20)或早期哺乳期(第1-3天)和对照雌性小鼠用补充有人的FXIA的Ig处理,然后进行氯化铁(FECL3)血管损伤。通过多普勒超声激光成像记录股骨静脉中的血液速度来评估血管的闭塞。通过在体外增加小鼠血浆中凝血酶产生的能力选择FXIA剂量。 FXIA在小鼠等离子体中产生了强大的凝血酶产生。在FECL3损伤之后,与单独的Ig或未治疗的对照相比,孕+患者接受IG的损伤和非孕小鼠患者展示股静脉血液速度的速度更快。体外,在血浆化血栓形成后血浆样品中的血浆产生升高,可以通过抗FXI抗体减少。我们的研究结果表明,静脉内施用的FXIA可能导致怀孕和非孕妇血管损伤部位的血栓形成。

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