Abnormal inflammation leads to maternal coagulopathies associated with placental haemostatic alterations in a rat model of foetal loss
Abnormal inflammation leads to maternal coagulopathies associated with placental haemostatic alterations in a rat model of foetal loss
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DOI：
10.1160/th11-09-0626
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发表时间：
2012-03-01
影响因子：
6.7
通讯作者：
Graham, Charles H.
中科院分区：
文献类型：
--
作者：
Falcon, Bani J.;Cotechini, Tiziana;Graham, Charles H.
自发性流产通常与异常的母体炎症和全身凝血功能障碍有关。然而，炎症在产科凝血病发展中的作用知之甚少。此外，关于全身凝血功能障碍是否与胎盘止血改变有关，以及这些局部改变是否导致胎儿结局阴性，仍存在疑问。使用一个模型的自发性胎儿损失，其中孕鼠给予单次注射细菌脂多糖（LPS），我们的特点是全身母体凝血状态后，使用血栓弹力图（TEG），全球止血测定，测量凝块形成的动力学LPS管理。在82%的LPS处理的大鼠中，全身性母体凝血病是明显的。具体而言，我们观察到阶段I，II和III弥漫性血管内凝血（DIC）和高凝状态。通过依那西普抑制肿瘤坏死因子a来调节炎症，导致表现出凝血功能障碍的大鼠比例降低62%。此外，炎症诱导的全身性凝血病与胎盘止血改变相关，包括DIC-I和高凝状态病例中血管内、蜕膜和迷路纤维蛋白沉积增加，以及DIC-III病例中几乎完全不存在纤维蛋白沉积。此外，全身和胎盘止血变化与子宫-胎盘血流动力学受损相关，依那西普对这些止血变化的抑制与子宫-胎盘血流动力学的维持相关。这些发现表明，母体炎症的调制可能有助于预防与妊娠并发症相关的凝血功能障碍。
Spontaneous pregnancy loss is often associated with aberrant maternal inflammation and systemic coagulopathies. However, the role of inflammation in the development of obstetric coagulopathies is poorly understood. Further, questions remain as to whether systemic coagulopathies are linked to placental haemostatic alterations, and whether these local alterations contribute to a negative foetal outcome. Using a model of spontaneous foetal loss in which pregnant rats are given a single injection of bacterial lipopolysaccharide (LPS), we characterised the systemic maternal coagulation status following LPS administration using thromboelastography (TEG), a global haemostatic assay that measures the kinetics of clot formation. Systemic maternal coagulopathy was evident in 82% of LPS-treated rats. Specifically, we observed stage-I, -II, and -III disseminated intravascular coagulation (DIC) and hypercoagulability. Modulation of inflammation through inhibition of tumour necrosis factor a with etanercept resulted in a 62% reduction in the proportion of rats exhibiting coagulopathy. Moreover, inflammation-induced systemic coagulopathies were associated with placental haemostatic alterations, which included increased intravascular, decidual, and labyrinth fibrin deposition in cases of DIC-I and hypercoagulability, and an almost complete absence of fibrin deposition in cases of DIC-III. Furthermore, systemic and placental haemostatic alterations were associated with impaired utero-placental haemodynamics, and inhibition of these haemostatic alterations by etanercept was associated with maintenance of utero-placental haemodynamics. These findings indicate that modulation of maternal inflammation may be useful in the prevention of coagulopathies associated with complications of pregnancy.