Beresford C H
Department of Pathology, Medical School, University of Otago, Dunedin, New Zealand.
Blood Rev. 1988 Dec;2(4):239-50. doi: 10.1016/0268-960x(88)90013-6.
A moderate reduction of plasma antithrombin activity is an uncommon but clinically important cause of severe thromboembolic disease. In recent years the molecule responsible for the major part of this activity (antithrombin III) has been extensively characterised and the mode of inheritance of familial deficiencies worked out. Over 30 autosomally dominant inheritable variants have been described, the gene for normal human antithrombin III has been sequenced and this information has provided important insights into the reaction of antithrombin with thrombin and the catalytic role of heparin. Further information has been derived by analogy with other serine proteinase inhibitors, in particular alpha 1 antitrypsin. Recombinant DNA methods have been used to produce functionally active AT III which may, in the future, replace human chromatographically-separated AT III as the treatment of choice for clinically important deficiency states. Newer diagnostic techniques, using restriction fragment length polymorphisms and synthetic oligonucleotide probes, hold the promise of more accurate diagnosis and diagnosis in the antenatal period in families possessing some of the fully characterised variants.
血浆抗凝血酶活性适度降低是严重血栓栓塞性疾病的一个罕见但临床上重要的病因。近年来，负责这种活性主要部分的分子（抗凝血酶III）已得到广泛表征，家族性缺陷的遗传模式也已明确。已描述了30多种常染色体显性遗传变异，正常人抗凝血酶III的基因已被测序，这些信息为抗凝血酶与凝血酶的反应以及肝素的催化作用提供了重要见解。通过与其他丝氨酸蛋白酶抑制剂，特别是α1抗胰蛋白酶进行类比，获得了更多信息。重组DNA方法已被用于生产具有功能活性的抗凝血酶III，未来它可能会取代通过色谱法分离的人抗凝血酶III，成为临床上重要缺陷状态的首选治疗方法。使用限制性片段长度多态性和合成寡核苷酸探针的更新诊断技术，有望在拥有一些已充分表征变异的家族中实现更准确的诊断以及产前诊断。
