Haematology, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital, Westmead, NSW 2145, Australia.
Sydney Centres for Thrombosis and Haemostasis, Sydney, NSW, Australia, Phone: +612 8890 6618.
Clin Chem Lab Med. 2019 May 27;57(6):873-882. doi: 10.1515/cclm-2018-1041.
Background Most guidelines and experts recommend against performance of thrombophilia testing in general, and specifically against testing patients on pharmacological anticoagulants, due to substantially increased risk of false positive identification. For example, vitamin K antagonist (VKA) therapy affects protein C (PC) and protein S (PS), as well as some clotting assays (e.g. as used to investigate activated PC resistance [APCR]). Although heparin may also affect clotting assays, most commercial methods contain neutralisers to make them 'insensitive' to therapeutic levels. Direct oral anticoagulants (DOACs) also affect a wide variety of thrombophilia assays, although most reported data has employed artificial in vitro spiked samples. Methods In the current report, data from our facility for the past 2.5 years has been assessed for all 'congenital thrombophilia' related tests, as evaluated against patient anticoagulant status. We processed 10,571 'thrombophilia' related test requests, including antithrombin (AT; n=3470), PC (n=3569), PS (n=3585), APCR (n=2359), factor V Leiden (FVL; n=2659), and prothrombin gene mutation (PGM; n=2103). Results As expected, VKA therapy affected PC and PS, and despite manufacturer claims, also APCR. Most assays, as suggested by manufacturers, were largely resistant to heparin therapy. DOACs' use was associated with falsely low APCR ratios (i.e. FVL-like effect) and somewhat unexpectedly, anti-Xa agents apixaban and rivaroxaban were also associated with lower AT and higher PS values. Conclusions It is concluded that ex-vivo data appears to confirm the potential for both false positive and false negative 'thrombophilia' events in patients on anticoagulant (including DOAC) treatment.
背景 由于假阳性识别的风险大大增加，大多数指南和专家建议一般不进行血栓形成倾向检测，特别是不建议在使用药物抗凝的患者中进行检测。例如，维生素 K 拮抗剂 (VKA) 治疗会影响蛋白 C (PC) 和蛋白 S (PS)，以及一些凝血检测（例如用于研究激活的蛋白 C 抵抗 [APCR]）。虽然肝素也可能影响凝血检测，但大多数商业方法都包含中和剂，使它们对治疗水平“不敏感”。直接口服抗凝剂 (DOAC) 也会影响广泛的血栓形成倾向检测，尽管大多数报告的数据都使用了人工体外加样样本。方法 在当前报告中，评估了过去 2.5 年我们机构的所有“先天性血栓形成倾向”相关检测的数据，这些数据是根据患者的抗凝状态评估的。我们处理了 10571 例“血栓形成倾向”相关检测请求，包括抗凝血酶 (AT; n=3470)、PC (n=3569)、PS (n=3585)、APCR (n=2359)、因子 V 莱顿突变 (FVL; n=2659) 和凝血酶原基因突变 (PGM; n=2103)。结果 正如预期的那样，VKA 治疗会影响 PC 和 PS，尽管制造商声称，也会影响 APCR。正如制造商所建议的那样，大多数检测在很大程度上不受肝素治疗的影响。DOAC 的使用与 APCR 比值的假性降低（即 FVL 样效应）有关，并且出人意料的是，抗 Xa 药物阿哌沙班和利伐沙班也与 AT 降低和 PS 值升高有关。结论 可以得出结论，体外数据似乎证实了抗凝（包括 DOAC）治疗患者中存在血栓形成倾向检测的假阳性和假阴性事件的可能性。
