Clinical review: molecular mechanisms underlying the role of antithrombin in sepsis.
Clinical review: molecular mechanisms underlying the role of antithrombin in sepsis.
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临床综述：抗凝血酶在败血症中作用的分子机制。
DOI：
10.1186/cc4822
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发表时间：
2006-02
期刊：
影响因子：
--
通讯作者：
Wiedermann CJ
中科院分区：
文献类型：
--
作者：
Wiedermann CJ
在弥散性血管内凝血（DIC）中，炎症激活和凝血之间存在广泛的串扰。内源性抗凝途径受到炎症的下调，从而降低了这些途径所具有的天然抗炎机制。旨在抑制凝血和炎症激活的支持策略在理论上可能是合理的，并且在实验和初步临床研究中已被发现是有益的。本综述汇集了抗凝血酶在炎症凝血激活中的生物学机制的现有实验和临床数据。临床前研究已经证明，即使是低剂量的肝素也会部分干扰抗凝血酶的治疗效果，并在细胞机制水平上证实了抗凝血酶在 DIC 中的调节作用。在此生物学背景下，对脓毒症抗凝血酶随机对照试验数据的重新分析表明，抗凝血酶有可能进一步开发为 DIC 治疗药物。尽管缺乏采用令人满意的方法的研究，但迄今为止对抗凝血酶作用机制进行的研究结果使人们可以推断出该药物的价值具有生物学合理性。然而，对该药物有效性的最终评估必须等待积极的、前瞻性的、随机的和安慰剂对照的研究的可用性。
In disseminated intravascular coagulation (DIC) there is extensive crosstalk between activation of inflammation and coagulation. Endogenous anticoagulatory pathways are downregulated by inflammation, thus decreasing the natural anti-inflammatory mechanisms that these pathways possess. Supportive strategies aimed at inhibiting activation of coagulation and inflammation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. This review assembles the available experimental and clinical data on biological mechanisms of antithrombin in inflammatory coagulation activation. Preclinical research has demonstrated partial interference of heparin – administered even at low doses – with the therapeutic effects of antithrombin, and has confirmed – at the level of cellular mechanisms – a regulatory role for antithrombin in DIC. Against this biological background, re-analyses of data from randomized controlled trials of antithrombin in sepsis suggest that antithrombin has the potential to be developed further as a therapeutic agent in the treatment of DIC. Even though there is a lack of studies employing satisfactory methodology, the results of investigations conducted thus far into the mechanisms of action of antithrombin allow one to infer that there is biological plausibility in the value of this agent. Final assessment of the drug's effectiveness, however, must await the availability of positive, prospective, randomized and placebo-controlled studies.
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影响因子：
38.9
作者：
Baudo, F;Caimi, TM;Calori, G
通讯作者：
Calori, G
影响因子：
20.3
作者：
Dunzendorfer, S;Kaneider, N;Wiedermann, CJ
通讯作者：
Wiedermann, CJ
影响因子：
20.3
作者：
Harada, N;Okajima, K;Tanaka, K
通讯作者：
Tanaka, K
影响因子：
2.2
作者：
ANDERSSON, LO;ENGMAN, L;HENNINGSSON, E
通讯作者：
HENNINGSSON, E
DOI：
10.1152/ajpcell.2000.279.1.c98
发表时间：
2000-07-01
影响因子：
5.5
作者：
Hoffmann, JN;Vollmar, B;Menger, MD
通讯作者：
Menger, MD