Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, CIBERER, Spain.
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, CIBERER, Spain.
Thromb Res. 2018 Sep;169:23-29. doi: 10.1016/j.thromres.2018.07.008. Epub 2018 Jul 5.
Antithrombin is a key endogenous anticoagulant whose deficiency constitutes a strong risk factor for thrombosis. The study of antithrombin deficiency has generated excellent, and in some cases, surprising results that may be extrapolated to other thrombophilia and genetic disorders. Routine diagnosis of antithrombin deficiency is based on functional assays. Few specialized laboratories also perform genetic analysis, even though nowadays it is a simple, fast and cheap process that generates relevant information with clinical usefulness. Molecular analysis of SERPINC1, the gene encoding antithrombin, has been restricted so far to cases with confirmed or familial antithrombin deficiency. However, some pathogenic mutations are not detected by current functional methods and other gene defects may have functional consequences only observed under specific conditions. Thus, molecular analysis may be the best method to identify antithrombin deficiency. Up to 80% of patients with antithrombin deficiency have SERPINC1 gene defects, mostly (90% of the 315 gene defects described so far) point mutations or small deletions or insertions affecting the 7 exons or flanking regions. The description of new SERPINC1 gene defects may reveal new residues with functional or structural relevance and new mechanisms causing deficiency of this endogenous anticoagulant. Moreover, other genes and mechanisms may also be involved in antithrombin deficiency. Thus, disorders of N-glycosylation explain up to 5% of cases with antithrombin deficiency. However, there are still up to 10-15% of cases with antithrombin deficiency of unknown cause, whose study may reveal new genes and mechanisms involved in thrombosis.
抗凝血酶是一种关键的内源性抗凝剂，其缺乏构成血栓形成的强烈危险因素。抗凝血酶缺乏的研究产生了出色的、在某些情况下令人惊讶的结果，这些结果可能可以外推到其他血栓形成和遗传疾病。抗凝血酶缺乏的常规诊断基于功能测定。少数专门实验室也进行基因分析，尽管目前这是一个简单、快速且廉价的过程，可以生成具有临床用途的相关信息。编码抗凝血酶的 SERPINC1 基因的分子分析迄今为止仅限于已确认或家族性抗凝血酶缺乏的病例。然而，目前的功能方法无法检测到一些致病性突变，并且其他基因缺陷可能仅在特定条件下具有功能后果。因此，分子分析可能是识别抗凝血酶缺乏的最佳方法。多达 80%的抗凝血酶缺乏症患者存在 SERPINC1 基因缺陷，主要是（迄今为止描述的 315 个基因缺陷中的 90%）影响 7 个外显子或侧翼区域的点突变或小缺失或插入。新的 SERPINC1 基因缺陷的描述可能揭示具有功能或结构相关性的新残基以及导致这种内源性抗凝剂缺乏的新机制。此外，其他基因和机制也可能参与抗凝血酶缺乏症。因此，N-糖基化障碍解释了多达 5%的抗凝血酶缺乏症病例。然而，仍有高达 10-15%的抗凝血酶缺乏症原因不明，对这些病例的研究可能揭示参与血栓形成的新基因和机制。
