狼疮抗凝检测中的分析困境

G. Moore
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引用次数: 0

摘要

准确的狼疮抗凝血剂(LA)检测对抗磷脂综合征(APS)的诊断至关重要。检测基于凝血测定中LA的功能行为,而不考虑表位特异性。LA筛选试验使用稀释的磷脂来增强LA的体外抑制作用,尽管它们不是LA特异性的,并且可以通过其他凝血异常而升高。强化筛选测试被反射为混合测试,以区分因子缺乏和抑制。高磷脂浓度的验证性试验使LA比筛选试验产生更短的凝血时间,而非磷脂依赖性抑制剂则能持续延长凝血时间。LA的异质性意味着没有单一的筛选测试能检测到每个LA,筛选/混合/确认混合物必须应用于至少两种检测类型,通常是稀释Russell毒蛇毒液时间(dRVVT)和LA敏感的活化部分凝血活酶时间(aPTT)。大多数实验室将LA检测限制在这两种检测,而其他检测,如稀释凝血酶原时间(dPT),可以以同等的诊断效果进行,并额外检测dRVVT和aPTT不反应的LA。将凝血时间转换为标准化比率可以提高测定性能,从业者必须在反映当天测定性能的正常合并血浆(NPP)凝血时间分母和抵消NPP变化影响的参考间隔(RI)平均凝血时间之间做出选择。截止值可以根据正态分布数据参数化生成,也可以根据敏感性和特异性之间的首选平衡应用不同的百分位数。为准确的截止估计寻找足够的捐助者是有问题的,可以在捐助者人数较少的情况下进行转移工作。混合测试的分析局限性导致了对筛选/混合/确认测试顺序采用替代算法,而尽管存在这些局限性,一些人仍继续严格应用后者。减少或消除治疗性抗凝作用的策略有局限性,而用ecarin时间(ET)验证试验进行的Taipan蛇毒时间(TSVT)筛选试验对维生素K拮抗剂(VKA)和直接激活因子X抗凝不敏感。
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Analytical dilemmas in lupus anticoagulant detection
Accurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, although they are not LA-specific and can be elevated by other coagulation abnormalities. Elevated screening tests are reflexed to mixing tests to distinguish between factor deficiency and inhibition. Confirmatory tests with high phospholipid concentration swamp LA to generate shorter clotting times than screening tests, whilst prolongation persists with non-phospholipid-dependent inhibitors. LA heterogeneity means that no single screening test detects every LA and the screen/mix/confirm medley must be applied to at least two assay types, usually dilute Russell’s viper venom time (dRVVT) and an LA-sensitive activated partial thromboplastin time (aPTT). Most laboratories restrict LA testing to these two assays, yet others, such as dilute prothrombin time (dPT), can perform with equal diagnostic efficacy, and additionally detect LA unreactive with dRVVT and aPTT. Converting clotting times to normalized ratios improves assay performance, and practitioners must choose between normal pooled plasma (NPP) clotting time denominators to reflect on-the-day assay performance, or reference interval (RI) mean clotting times to negate the effects of NPP variation. Cut-offs can be generated parametrically from normally distributed data, or different percentiles applied depending on the preferred balance between sensitivity and specificity. Sourcing sufficient donors for accurate cut-off estimations is problematic and transference exercises can be undertaken on low donor numbers. Analytical limitations of mixing tests have led to the adoption of alternative algorithms to the screen/mix/confirm test order, whilst some continue to rigidly apply the latter despite those limitations. Strategies to reduce or eliminate the effects of therapeutic anticoagulation have limitations, whilst the Taipan snake venom time (TSVT) screening test with an ecarin time (ET) confirmatory test is insensitive to vitamin K antagonist (VKA) and direct activated factor X anticoagulation.
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