Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK.
Int J Lab Hematol. 2011 Jun;33(3):227-37. doi: 10.1111/j.1751-553X.2011.01307.x. Epub 2011 Mar 15.
Antithrombin (AT) deficiency is associated with an increased risk of deep vein thrombosis and pulmonary embolism which are major causes of morbidity and death. The incidence of deficiency in healthy populations has been reported to vary from 1/600 to 1/5000, with the variation being due to the different populations studied and detection methods used. When reduced activity levels are identified it is important to measure the AT antigen levels to differentiate type I from type II disorders, as type II defects have varying thrombotic risk.
Functional AT assays detect the ability of AT to inactivate thrombin or factor Xa, and AT antigen assays detect the quantity of AT in plasma. In functional assays, reducing the incubation time of sample with enzyme/heparin reagent may increase sensitivity to type II defects. An excess of antigen over activity level suggests the presence of functionally defective AT, which can be characterized further by assaying AT in the absence of heparin, electrophoresis to investigate the ability of heparin to bind to AT, and gene sequencing.
Many patients with AT deficiency have a type II defect and these defects may not be detected by all routine diagnostic assays. Assays using human thrombin may lack specificity and assays that use factor Xa may fail to detect the common variant, AT Cambridge II, which can be detected by assays using bovine thrombin, especially if activity is compared to antigen by ratio. Factor Xa based assays may be particularly sensitive to certain heparin binding defects, and sensitivity of assays to both heparin binding and reactive site defects can be improved by shortening the incubation time with enzyme.
uAT activity assays are essential for the detection of AT deficiency because type II defects are relatively common in patients with heritable deficiency. No one functional assay can be assumed to detect all forms of AT deficiency, and assays can sometimes be improved by reducing reaction time of AT with thrombin or factor Xa.
抗凝血酶（AT）缺乏与深静脉血栓形成和肺栓塞的风险增加有关，这些是发病率和死亡率的主要原因。健康人群中缺乏的发生率据报道在 1/600 至 1/5000 之间变化，这种变化是由于所研究的人群不同和使用的检测方法不同。当发现活性水平降低时，测量 AT 抗原水平以区分 I 型和 II 型疾病非常重要，因为 II 型缺陷具有不同的血栓形成风险。
功能性 AT 测定法检测 AT 灭活凝血酶或因子 Xa 的能力，AT 抗原测定法检测血浆中 AT 的量。在功能测定中，缩短样品与酶/肝素试剂的孵育时间可能会提高对 II 型缺陷的敏感性。抗原量超过活性水平表明存在功能缺陷的 AT，可以通过在没有肝素的情况下进一步测定 AT、电泳研究肝素结合 AT 的能力以及基因测序来进一步表征。
许多 AT 缺乏症患者存在 II 型缺陷，并非所有常规诊断测定法都能检测到这些缺陷。使用人凝血酶的测定法可能缺乏特异性，而使用因子 Xa 的测定法可能无法检测到常见的变体 AT Cambridge II，该变体可以通过使用牛凝血酶的测定法检测到，特别是如果将活性与抗原的比值进行比较时。基于因子 Xa 的测定法可能对某些肝素结合缺陷特别敏感，通过缩短与酶的孵育时间，可以提高对肝素结合和反应部位缺陷的测定法的敏感性。
uAT 活性测定法对于检测 AT 缺乏症至关重要，因为遗传性缺乏症患者中 II 型缺陷相对常见。不能假定任何一种功能测定法都能检测到所有形式的 AT 缺乏症，并且通过缩短 AT 与凝血酶或因子 Xa 的反应时间，有时可以改进测定法。
