Hemostasis Laboratory, Finnish Red Cross Blood Service, Helsinki, Finland.
J Thromb Haemost. 2013 Oct;11(10):1844-9. doi: 10.1111/jth.12364.
It has been shown that some antithrombin (AT) activity assays do not correctly detect inherited type II AT deficiency, but erroneously classify these patients as normal.
Our aim was to investigate the mutations causing type II AT deficiency and to correlate the AT activity results with the genetic findings.
PATIENTS/METHODS: A large population (n = 104; 42 families) of Finnish patients with known AT type II deficiency were interviewed for clinical data. Their AT activity was measured with five commercially available methods, and the SERPINC1 gene was genotyped.
The mutations detected in type II AT-deficient patients were as follows: p.Pro73Leu (AT Basel) in 37 of 42 (88.1%) families; and p.Val30Glu, p.Arg425Cys and p.Pro439Ala in one family each. In two families, no mutation was detected. In the carriers of AT Basel two AT activity assays correctly identified most of the patients as AT-deficient, whereas three assays misclassified almost all of these patients as normal. Carriers of the founder mutation had, in addition to an elevated risk of venous thrombosis, a high risk of arterial thrombosis at young age, especially stroke.
In Finland, a population with a strong founder effect, AT type II deficiency is caused predominantly by a single point mutation, p.Pro73Leu. The mutation is associated with a significant thrombotic risk. Reduced AT activity caused by this mutation cannot be detected by all available screening methods. This must be taken into account in the choice of laboratory method used for screening.
已有研究表明，某些抗凝血酶（AT）活性检测方法无法正确检测遗传性 II 型 AT 缺乏症，反而错误地将这些患者归类为正常。
我们旨在研究导致 II 型 AT 缺乏症的突变，并将 AT 活性结果与遗传发现相关联。
患者/方法：对来自芬兰的已知 II 型 AT 缺乏症的大型患者群体（n=104；42 个家族）进行了临床数据访谈。使用五种市售方法测量他们的 AT 活性，并对 SERPINC1 基因进行了基因分型。
在 II 型 AT 缺陷患者中检测到的突变如下：在 42 个家族中的 37 个（88.1%）家族中发现 p.Pro73Leu（AT Basel）；在一个家族中发现 p.Val30Glu、p.Arg425Cys 和 p.Pro439Ala 各一个。在两个家族中未检测到突变。在 AT Basel 的携带者中，两种 AT 活性检测方法正确地将大多数患者识别为 AT 缺乏症，而三种检测方法几乎将所有这些患者错误地归类为正常。该创始突变的携带者除了静脉血栓形成的风险增加外，还存在年轻时动脉血栓形成的高风险，尤其是中风。
在芬兰，由于强烈的创始效应，人群中主要由单个点突变，即 p.Pro73Leu 引起 II 型 AT 缺乏症。该突变与显著的血栓形成风险相关。这种突变导致的 AT 活性降低不能被所有现有的筛选方法检测到。在选择用于筛选的实验室方法时，必须考虑到这一点。
