Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.
Departments of Obstetrics and Gynecology, Population Health and Environmental Medicine, New York University School of Medicine, New York, NY, USA.
J Thromb Haemost. 2017 Jul;15(7):1412-1421. doi: 10.1111/jth.13699. Epub 2017 Jun 12.
Essentials Annexin A5 resistance is a mechanism for antiphospholipid (aPL) syndrome. 750 patients with history of thrombosis, pregnancy complications and controls were tested. Reduced annexin A5 anticoagulant ratios (A5R) correlate with aPL antibody multipositivity. Reduced A5R may identify patients with a propensity for thrombosis or pregnancy complications. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini SUMMARY: Background Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with annexin A5 crystallization and anticoagulant activity. Objective The purpose of this study was to investigate whether reduced values in the annexin A5 anticoagulant ratio (A5R) assay (i.e. 'annexin A5 resistance') are associated with adverse clinical events in aPL antibody-positive patients. Patients/Methods In an initial discovery phase, a group of 679 patient samples from a 'real-world' tertiary care hospital population were tested for A5R. This was followed by a validation-phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history of an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. Results In the discovery-phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared with aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery-phase group and validation-phase cohort correlated with the extent of multi-positivity for standard APS tests, which has also been shown to be associated with a risk of adverse clinical outcomes. Conclusion Reduced A5R values were associated with a multi-positivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events.
抗磷脂（aPL）综合征的机制是 Annexin A5 耐药。对 750 例有血栓形成史、妊娠并发症和对照组的患者进行了检测。降低的 Annexin A5 抗凝比值（A5R）与 aPL 抗体多阳性相关。降低的 A5R 可能识别出有血栓形成或妊娠并发症倾向的患者。点击此处收听 ISTH 学院关于 Drs de Laat 和 Bertolaccini 抗磷脂抗体综合征的演讲总结：背景 Annexin A5（A5）是一种有效的抗凝蛋白，可阻止阴离子磷脂与凝血反应。先前的研究表明，来自抗磷脂（aPL）综合征（APS）患者的抗体干扰 Annexin A5 结晶和抗凝活性。目的本研究旨在探讨 Annexin A5 抗凝比值（A5R）检测中降低值（即“Annexin A5 耐药”）是否与 aPL 抗体阳性患者的不良临床事件相关。患者/方法在初始发现阶段，对来自三级护理医院人群的 679 例患者样本进行了 A5R 检测。随后是一个验证阶段队列，该队列包括 71 例无症状的 aPL 抗体阳性且无不良临床事件史的患者，对其基线样本进行 A5R 检测，然后观察长达 4 年。结果在发现阶段组中，我们发现与 aPL 抗体阴性患者和对照组相比，血栓形成和/或妊娠并发症的 aPL 抗体阳性患者的 A5R 降低。此外，发现阶段组和验证阶段队列中降低的 A5R 值与标准 APS 检测的多阳性程度相关，这也与不良临床结局的风险相关。结论在两个组中，降低的 A5R 值与 aPL 抗体阳性患者的多阳性谱相关，并且与不良临床事件的发生相关。
