Antithrombin.
Antithrombin.
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DOI：
10.1007/978-1-62703-339-8_28
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Karlaftis, Vasiliki
中科院分区：
文献类型：
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作者：
Hepner, Mirta;Karlaftis, Vasiliki
抗凝血酶（AT）是一种肝素辅因子，是丝氨酸蛋白酶抑制剂家族（丝氨酸蛋白酶抑制剂）的成员。成熟的AT分子由432个氨基酸组成，主要在肝脏中产生。最初，报告了血浆中几种不同的AT活性，导致抗凝血酶的分类范围从I到IV。随后表明，这些不同的抗凝血酶活性是一种分子的功能，抗凝血酶III，其名称在1993年国际血栓形成和止血学会会议上被简化为抗凝血酶。AT是凝血酶和Xa因子的重要蛋白酶抑制剂。然而，AT也能够抑制因子IXa、XIa、XIIab、激肽释放酶和纤溶酶。鉴于AT是凝血的主要天然存在的抑制剂之一，该蛋白质的获得性或遗传性缺陷导致过量的凝血酶生成。由于大量的突变是导致遗传性AT缺陷的原因，通过DNA测试筛选它们的存在需要对涉及许多外显子的每个完整基因进行测序。此外，基因突变的知识并不能为受影响家族的治疗提供任何益处，因此常规分子表征并不具有指示性。这些缺陷通过功能或免疫学测定来检测。AT酰胺分解试验建议用于AT缺乏症的初始检测。不需要常规进行AT免疫学测定。然而，它们是有用的，以区分I型和II型遗传性AT缺乏症。
Antithrombin (AT) is a heparin cofactor and a member of the serine protease inhibitor family (serpin). The mature AT molecule is composed of 432 amino acids and it is produced mainly in the liver. Initially, several different AT activities in plasma were reported, leading to the classification of antithrombin in a range from I to IV. It was subsequently shown that these various antithrombin activities were the function of one molecule, antithrombin III, whose name was reduced to antithrombin at the meeting of the International Society in Thrombosis and Haemostasis in 1993. AT is an important protease inhibitor of thrombin and factor Xa. However, AT is also able to inhibit factors IXa, XIa, XIIab, kallikrein, and plasmin. Given that AT is one of the major naturally occurring inhibitors of coagulation, acquired or hereditary deficiencies of this protein result in excessive thrombin generation. As a vast array of mutations are responsible for hereditary AT deficiencies, screening for their presence by DNA testing would require sequencing each entire gene involving numerous exons. Moreover, the knowledge of the gene mutation does not offer any benefit in the treatment of affected families, so the routine molecular characterization is not indicative. These defects are detected by functional or immunological assays. AT amidolytic assays are recommended for initial testing for AT deficiency. There is no need to routinely perform AT immunological assays. However, they are useful in order to distinguish type I from type II hereditary AT deficiency.