Research and Development, Technoclone Herstellung von Diagnostika und Arzneimitteln GmbH, Vienna, Austria.
Specialist Haemostasis Unit, Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Methods Mol Biol. 2023;2663:263-274. doi: 10.1007/978-1-0716-3175-1_16.
Testing for lupus anticoagulants (LA) in the presence of therapeutic anticoagulation is largely discouraged because of the risk of false-positive and false-negative results, although the ability to detect LA in this setting can be clinically valuable. Strategies such as mixing tests and anticoagulant neutralization can be effective, but have their own limitations. The prothrombin activators in venoms from Coastal Taipan and Indian saw-scaled viper snakes provide an additional analytical avenue in that they are insensitive to the effects of vitamin K antagonists and inevitably bypass the effects of direct factor Xa inhibitors. Oscutarin C in Coastal Taipan venom is phospholipid- and Ca-dependent, so the venom is used in a dilute phospholipid design as an LA screening test called the Taipan snake venom time (TSVT). The ecarin fraction of Indian saw-scaled viper venom is cofactor-independent and operates as a prothrombin-activated confirmatory test, the ecarin time, because the absent phospholipid precludes inhibition by LAs. Bypassing all coagulation factors except prothrombin and fibrinogen renders the assays innately more specific than other LA assays, while TSVT as a screening test has good sensitivity to LAs detected in other assays, as well as occasional antibodies unreactive in other assays.
在治疗性抗凝的情况下检测狼疮抗凝物(LA),由于存在假阳性和假阴性的风险,因此基本上不被鼓励,尽管在此情况下检测 LA 的能力可能具有临床价值。混合测试和抗凝剂中和等策略可能有效,但也有其自身的局限性。来自沿海太攀蛇和印度锯鳞蝰蛇毒液中的凝血酶原激活剂为我们提供了另一种分析途径,因为它们对维生素 K 拮抗剂的作用不敏感,并且不可避免地绕过直接因子 Xa 抑制剂的作用。沿海太攀蛇毒液中的 Oscutarin C 是磷脂和 Ca 依赖性的,因此将毒液以稀释的磷脂设计形式用于 LA 筛选测试,称为太攀蛇毒时间(TSVT)。印度锯鳞蝰蛇毒液中的 ecarin 部分是辅因子非依赖性的,作为凝血酶原激活的确认测试(ecarin 时间),因为缺乏磷脂会阻止 LA 的抑制作用。除了凝血酶原和纤维蛋白原之外,绕过所有凝血因子使得这些检测方法比其他 LA 检测方法固有地更具特异性,而 TSVT 作为筛选测试对其他检测方法中检测到的 LA 具有良好的敏感性,以及在其他检测方法中反应不灵敏的偶尔抗体。