Diagnostic Haemostasis Laboratory, Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia.
Sydney Centres for Thrombosis and Haemostasis, Westmead, New South Wales, Australia.
Semin Thromb Hemost. 2019 Feb;45(1):22-35. doi: 10.1055/s-0038-1677018. Epub 2019 Jan 10.
The activated partial thromboplastin time (APTT) assay is a very common coagulation test, used for several reasons. The test is conventionally used for assessing the contact factor (intrinsic) pathway of blood coagulation, and thus for screening deficiencies in this pathway, most typically factors VIII, IX, and XI. The APTT is also sensitive to contact factor deficiencies, including factor XII, prekallikrein, and high-molecular-weight kininogen. The APTT may also be elevated in a variety of conditions, including liver disease, vitamin K deficiency, and disseminated intravascular coagulation. The APTT can also be used for monitoring unfractionated heparin (UFH) therapy, as well as for screening lupus anticoagulant (LA) or for assessing thrombosis risk. Which of these separate uses is important to a given laboratory or clinician depends on the laboratory and the clinical context. For example, UFH sensitivity is important in hospital-based laboratories, where UFH therapy is used, but not in hospital-based laboratories where low-molecular-weight heparin (LMWH) is largely employed or where UFH may be assessed by anti-factor Xa testing, or in private/community laboratories not associated with a hospital system. High sensitivity to (low levels of) factors VIII, IX, and XI is generally preferred, as their deficiencies are clinically significant. Also preferred, but not usually achieved, is low sensitivity to factor XII and other contact factors, as these deficiencies are usually asymptomatic. Nevertheless, a good knowledge of factor sensitivity is usually needed, if only to help explain the reasons for a prolonged APTT in a given patient, or whether factor testing or other investigation is required. A good working knowledge of reagents sensitivity to LA is also advisable, especially when the reagent is used as part of a LA test panel, or else as a "general-purpose screening reagent." The current report is aimed at providing some guidance around these questions, and is intended as a kind of "how to" guide, that will enable laboratories to assess APTT reagents in regard to their sensitivity to heparin, LA, and clotting factors. The report also provides some advice on generation of normal reference ranges, as well as solutions for troubleshooting prolonged APTTs, when performing factor testing or searching for inhibitors.
活化部分凝血活酶时间（APTT）检测是一种非常常见的凝血检测，有多种用途。该检测常用于评估接触因子（内在）凝血途径，因此用于筛查该途径的缺陷，最常见的是因子 VIII、IX 和 XI。APTT 对接触因子缺陷也很敏感，包括因子 XII、前激肽释放酶和高分子量激肽原。APTT 也可在多种情况下升高，包括肝脏疾病、维生素 K 缺乏和弥漫性血管内凝血。APTT 还可用于监测未分级肝素（UFH）治疗，筛查狼疮抗凝物（LA）或评估血栓形成风险。给定实验室或临床医生认为哪种用途重要，取决于实验室和临床情况。例如，UFH 敏感性在使用 UFH 治疗的医院实验室很重要，但在使用低分子量肝素（LMWH）的医院实验室或可能通过抗因子 Xa 检测评估 UFH 的实验室，或与医院系统无关的私人/社区实验室并不重要。通常优选对（低水平的）因子 VIII、IX 和 XI 具有高灵敏度，因为它们的缺陷具有临床意义。也优选但通常无法实现对因子 XII 和其他接触因子的低灵敏度，因为这些缺陷通常无症状。然而，如果只是为了帮助解释特定患者 APTT 延长的原因，或者是否需要进行因子检测或其他检查，通常需要很好地了解因子的敏感性。还建议对 LA 试剂的敏感性有很好的了解，特别是当试剂用作 LA 检测试剂盒的一部分，或者用作“通用筛选试剂”时。本报告旨在围绕这些问题提供一些指导，并旨在成为一种“如何做”的指南，使实验室能够评估 APTT 试剂对肝素、LA 和凝血因子的敏感性。该报告还就生成正常参考范围以及在进行因子检测或寻找抑制剂时解决延长 APTT 的问题提供了一些建议。
