Mackie Ian, Cooper Peter, Kitchen Steve
Haemostasis Research Unit, Haematology Department, University College London, London, UK.
Semin Hematol. 2007 Apr;44(2):114-25. doi: 10.1053/j.seminhematol.2007.01.001.
The consequences of an erroneous thrombophilia diagnosis may be serious if it is used to determine clinical management. Therefore careful selection, assessment, and control of laboratory tests for thrombophilia are essential. As for other coagulation tests, the pre-analytical phase must be carefully controlled with attention to the specific problems associated with each type of assay. The investigator must then recognize that for most laboratory tests of thrombophilia, there are a number of assay types available, often based on different principles of analysis. This creates the potential for different users to obtain varying results depending on the technique employed. Such problems can occur in assays of antithrombin activity, depending on whether the assay employs factor Xa, human thrombin, or bovine thrombin. In clot-based assays of protein C and protein S, there can be specificity problems related to interference by factor V Leiden (FVL), antiphospholipid antibodies, and other substances. Even genetic tests can give erroneous results and should not automatically be seen as absolute without supporting evidence and careful quality-control measures. Whatever technique is selected, it is mandatory to incorporate sufficient concurrent quality-control samples to validate the results of thrombophilia tests. These should include assessment of the parameter at normal and abnormal levels to give confidence in results across the measurement range that would normally be encountered in routine practice. This should be used in conjunction with regular participation in external quality assessment (EQA) (which has been linked to improved laboratory performance in thrombophilia testing). Larger EQA programs can provide information concerning the relative performance of analytical procedures, including the method principle, reagents, and instruments. Herein, we describe many of the methodologic effects in detail. We use specific examples to illustrate the general principle that, in performing laboratory testing for thrombophilia, one must always consider the performance characteristics and limitations of the assay in use.
如果错误的血栓形成倾向诊断用于确定临床管理，其后果可能很严重。因此，仔细选择、评估和控制血栓形成倾向的实验室检测至关重要。与其他凝血检测一样，分析前阶段必须仔细控制，注意每种检测方法相关的特定问题。研究人员必须认识到，对于大多数血栓形成倾向的实验室检测，有多种检测类型可供选择，通常基于不同的分析原理。这就有可能导致不同用户根据所采用的技术获得不同的结果。这种问题可能出现在抗凝血酶活性检测中，具体取决于检测是使用因子Xa、人凝血酶还是牛凝血酶。在基于凝血块的蛋白C和蛋白S检测中，可能存在与因子V莱顿（FVL）、抗磷脂抗体和其他物质干扰相关的特异性问题。即使是基因检测也可能给出错误结果，在没有支持证据和仔细的质量控制措施的情况下，不应自动将其视为绝对准确。无论选择何种技术，都必须纳入足够的同步质量控制样本以验证血栓形成倾向检测的结果。这些样本应包括对正常和异常水平参数的评估，以便对常规实践中通常会遇到的整个测量范围内的结果有信心。这应与定期参加外部质量评估（EQA）（这与血栓形成倾向检测中实验室性能的改善有关）相结合使用。更大规模的EQA计划可以提供有关分析程序相对性能的信息，包括方法原理、试剂和仪器。在此，我们详细描述了许多方法学影响。我们用具体例子来说明一般原则，即在进行血栓形成倾向的实验室检测时，必须始终考虑所使用检测方法的性能特征和局限性。
