Haemostasis Laboratory, Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2065, Australia.
Semin Thromb Hemost. 2013 Apr;39(3):283-90. doi: 10.1055/s-0033-1336832. Epub 2013 Mar 2.
Mixing tests are a relatively simple procedure used in the hemostasis laboratory as a first-line investigation into the cause of an abnormal screening test, typically a prolonged activated partial thromboplastin time and/or a prolonged prothrombin time. The mixing test involves combining the test plasma with normal plasma, then repeating the screening test on the mixture to assess whether the clotting time becomes normal or remains prolonged. The primary purpose of a mixing test is to guide further investigations. When mixing test results "normalize," this suggests the test plasma is deficient in clotting factor(s) and thus specific factor assays can be performed to determine which are reduced. When the mixing test result does not "normalize," this suggests the presence of an inhibitor or other type of interference (e.g., the presence of an anticoagulant such as high-dose heparinoids), and so the laboratory needs to determine if this is a lupus anticoagulant or a specific coagulation factor inhibitor, or another type of inhibitor. Because these follow-up investigations are more costly and time-consuming than the basic screening tests, the appropriate performance and interpretation of mixing tests is advantageous for the laboratory. Moreover, the correct laboratory approach is also clinically relevant, as patient management is ultimately affected, and an incorrect interpretation may lead to inappropriate therapies being established. Components of a mixing test that can influence result interpretation include the sensitivity of the used screening reagents to various factor deficiencies and inhibitors, the source or composition of the normal plasma, and the setting of cutoffs for the formula used in expressing mixing test results. Numerous and differing criteria for mixing test interpretation have been suggested historically, which can lead to confusion as to which approach is the most appropriate. The use of differing criteria will also lead to differing interpretations regarding "normalization." For this pivotal reason, standardized mixing test procedures and a consistent set of validated interpretive criteria represent the most favorable approach to maximizing the utility of a mixing test, and ensure the most accurate diagnosis for investigated patients.
混合测试是止血实验室中一种相对简单的程序,作为对异常筛选测试原因的一线调查,通常是延长的激活部分凝血活酶时间和/或延长的凝血酶原时间。混合测试包括将测试血浆与正常血浆混合,然后在混合物上重复筛选测试,以评估凝血时间是否正常或仍然延长。混合测试的主要目的是指导进一步的调查。当混合测试结果“正常化”时,这表明测试血浆缺乏凝血因子(s),因此可以进行特定因子测定以确定哪些因子减少。当混合测试结果未“正常化”时,这表明存在抑制剂或其他类型的干扰(例如,存在抗凝剂如高剂量肝素类药物),因此实验室需要确定这是狼疮抗凝剂还是特定凝血因子抑制剂,或其他类型的抑制剂。由于这些后续调查比基本筛选测试更昂贵和耗时,因此适当的混合测试性能和解释对实验室有利。此外,正确的实验室方法也与临床相关,因为患者管理最终会受到影响,并且不正确的解释可能导致建立不适当的治疗方法。影响结果解释的混合测试的组成部分包括用于各种因子缺乏症和抑制剂的筛选试剂的敏感性、正常血浆的来源或组成,以及用于表达混合测试结果的公式的截止值。历史上已经提出了许多不同的混合测试解释标准,这可能导致对哪种方法最合适的混淆。使用不同的标准也会导致关于“正常化”的不同解释。出于这个关键原因,标准化的混合测试程序和一致的一套经过验证的解释标准代表了最大限度地利用混合测试的最有利方法,并确保对接受调查的患者进行最准确的诊断。