Clin Chem Lab Med. 2014 Dec;52(12):1797-806. doi: 10.1515/cclm-2014-0246.
Antithrombin (AT) is a slow-acting progressive inhibitor of activated clotting factors, particularly thrombin and activated factor X (FXa). However, the presence of heparin or heparan sulfate accelerates its effect by several magnitudes. AT deficiency, a severe thrombophilia, is classified as type I (quantitative) and type II (qualitative) deficiency. In the latter case mutations may influence the reactive site, the heparin binding-site (HBS) and exert pleiotropic effect. Heterozygous type II-HBS deficiency is a less severe thrombophilia than other heterozygous subtypes. However, as opposed to other subtypes, it also exists in homozygous form which represents a very high risk of venous thromboembolism.
A modified anti-FXa chromogenic AT assay was developed which determines both the progressive (p) and the heparin cofactor (hc) activities, in parallel. The method was evaluated and reference intervals were established. The usefulness of the assay in detecting type II-HBS AT deficiency was tested on 78 AT deficient patients including 51 type II-HBS heterozygotes and 18 homozygotes.
Both p-anti-FXa and hc-anti-FXa assays showed excellent reproducibility and were not influenced by high concentrations of triglyceride, bilirubin and hemoglobin. Reference intervals for p-anti-FXa and hc-anti-FXa AT activities were 84%-117% and 81%-117%, respectively. Type II-HBS deficient patients demonstrated low (heterozygotes) or very low (homozygotes) hc-anti-FXa activity with normal or slightly decreased p-anti-FXa activity. The p/hc ratio clearly distinguished wild type controls, type II-HBS heterozygotes and homozygotes.
Concomitant determination of p-anti-FXa and hc-anti-FXa activities provides a reliable, clinically important diagnosis of type II-HBS AT deficiency and distinguishes between homozygotes and heterozygotes.
抗凝血酶（AT）是一种作用缓慢的活化凝血因子的渐进抑制剂，特别是凝血酶和活化因子 X（FXa）。然而，肝素或硫酸乙酰肝素的存在可使其作用加速几个数量级。AT 缺乏症是一种严重的血栓形成倾向，分为 I 型（定量）和 II 型（定性）缺乏症。在后一种情况下，突变可能会影响反应部位、肝素结合部位（HBS）并产生多效性效应。杂合子 II-HBS 缺乏症是一种比其他杂合子亚型较轻的血栓形成倾向。然而，与其他亚型不同的是，它也存在于纯合子形式中，这代表着静脉血栓栓塞的极高风险。
开发了一种改良的抗 FXa 显色 AT 测定法，该测定法可同时平行测定渐进性（p）和肝素辅因子（hc）活性。对该方法进行了评估并建立了参考区间。该测定法在 78 名 AT 缺乏症患者中检测 II-HBS AT 缺乏症的有用性，包括 51 名 II-HBS 杂合子和 18 名纯合子。
p-抗 FXa 和 hc-抗 FXa 测定均显示出极好的可重复性，并且不受高浓度甘油三酯、胆红素和血红蛋白的影响。p-抗 FXa 和 hc-抗 FXa AT 活性的参考区间分别为 84%-117%和 81%-117%。II-HBS 缺乏症患者表现出低（杂合子）或极低（纯合子）的 hc-抗 FXa 活性，而 p-抗 FXa 活性正常或略有降低。p/hc 比值清楚地区分了野生型对照、II-HBS 杂合子和纯合子。
同时测定 p-抗 FXa 和 hc-抗 FXa 活性可提供 II-HBS AT 缺乏症的可靠、临床重要的诊断，并区分纯合子和杂合子。
