IMPACT OF OBESITY ON ENDOTOXIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION
IMPACT OF OBESITY ON ENDOTOXIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION
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DOI：
10.1097/shk.0000000000000428
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发表时间：
2015-10-01
期刊：
影响因子：
3.1
通讯作者：
Jourdain, Merce
中科院分区：
文献类型：
--
作者：
Duburcq, Thibault;Tournoys, Antoine;Jourdain, Merce
脓毒症时凝血和纤维蛋白溶解的早期激活，导致弥散性血管内凝血（DIC）综合征。肥胖已被证明是一种高凝和低纤溶状态，但其对DIC的影响从未被研究过。在这项研究中，我们的目的是确定是否肥胖损害DIC在急性内毒素休克模型使用小型猪。这是一项经动物伦理委员会批准的前瞻性、比较性和实验性辅助研究。选择猪作为临床相关种属，其凝血反应与人类相似。研究了四组五只尤卡坦小型猪：瘦和肥胖对照组，瘦脂多糖（LPS）组接受大肠杆菌内毒素（LPS），肥胖LPS组接受相同的内毒素剂量。我们测量了标准凝血参数（凝血酶原时间[PT]、血小板计数和纤维蛋白原水平）、凝血酶-抗凝血酶复合物、组织型纤溶酶原激活物和纤溶酶原激活物抑制剂-1。所有测量均在基线和30、60、90、150和300分钟时进行。结果以中位数和四分位数范围表示。基线时，血小板计数（477 [428 - 532] G/L vs. 381 [307 - 442] G/L; P = 0.005）和纤维蛋白原水平（4.6 [3.8 - 5.2] g/L vs. 2 [1.8 - 2.9] g/L; P < 0.001）显著较高，而PT（80% [76% - 92%] vs. 96% [89% - 100%]; P = 0.01）在肥胖猪中显著低于瘦肉猪。内毒素组出现典型的低动力性休克伴DIC。与瘦型LPS组相比，肥胖型LPS组凝血参数（PT、血小板计数和纤维蛋白原水平）的降低和凝血酶-抗凝血酶复合物的增加（150 min时581 [382 - 1，057] mg/mL vs. 247 [125 - 369] mg/mL; P = 0.03）显著更重要。关于纤维蛋白溶解反应，我们发现在300分钟时肥胖LPS组中纤溶酶原激活物抑制剂-1的增加略高（481 [365 - 617] ng/mL vs. 355 [209 - 660] ng/mL; P = 0.66）。在我们的内毒素休克模型中，肥胖猪发生了更严重的DIC，并伴有更严重的促凝血反应。
An early activation of coagulation and fibrinolysis occurs during sepsis, leading to the syndrome of disseminated intravascular coagulation (DIC). Obesity has been demonstrated to be a hypercoagulable and hypofibrinolytic state, but its impact on DIC has never been studied. In this study, we aimed to determine if obesity impairs DIC in an acute endotoxic shock model using minipigs. This was a prospective, comparative, and experimental ancillary study approved by the Animal Ethics Committee. Pigs were chosen as a clinically relevant species, resembling humans in coagulation reactions. Four groups of five "Yucatan'' minipigs were studied: lean and obese control groups, a lean lipopolysaccharide (LPS) group receiving Escherichia coli endotoxin (LPS), and an obese LPS group receiving the same endotoxin dose. We measured standard coagulation parameters (prothrombin time [PT], platelet count, and fibrinogen levels), thrombin-antithrombin complexes, tissue-type plasminogen activator, and plasminogen activator inhibitor-1. All measurements were performed at baseline and 30, 60, 90, 150, and 300 min. Results were given as median with interquartile ranges. At baseline, platelet count (477 [428 - 532] G/L vs. 381 [307 - 442] G/L; P = 0.005) and fibrinogen levels (4.6 [3.8 - 5.2] g/L vs. 2 [1.8 - 2.9] g/L; P < 0.001) were significantly higher, whereas PT (80% [76% - 92%] vs. 96% [89% - 100%]; P = 0.01) was significantly lower in obese pigs compared with lean pigs. In the LPS groups, administration of endotoxin resulted in a typical hypokinetic shock with DIC. The decrease in coagulation parameters (PT, platelet count, and fibrinogen levels) and the increase in thrombin-antithrombin complexes (581 [382 - 1,057] mg/mL vs. 247 [125 - 369] mg/mL at 150 min; P = 0.03) were significantly more important in the obese LPS group compared with those in the lean LPS group. Concerning the fibrinolytic reaction, we found a slightly more elevated increase of plasminogen activator inhibitor-1 in the obese LPS group at 300 min (481 [365 - 617] ng/mL vs. 355 [209 - 660] ng/mL; P = 0.66). In our model of endotoxic shock, obese pigs developed a more severe DIC with a more severe procoagulant response.