凝血酶生成试验和狼疮抗凝物协同区分抗磷脂抗体患者人群。
Thrombin generation assay and lupus anticoagulant synergically distinguish populations of patients with antiphospholipid antibodies.
机构信息
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK- net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley (North-West Italy), San Giovanni Bosco Hub Hospital and University of Turin, Turin, Italy.
出版信息
J Clin Pathol. 2023 Dec;76(12):839-846. doi: 10.1136/jcp-2022-208199. Epub 2022 Sep 13.
AIM
To apply thrombin generation assay (TGA) in a large cohort of antiphospholipid antibodies (aPL)-positive patients.
MATERIAL AND METHODS
108 patients were tested with TGA and lupus anticoagulant (LA) testing and divided according to their aPL profile. Briefly, 21 patients were positive for anti-phosphatidylserine (aPS)/prothrombin (PT) IgG/IgM (group1), 29 for anti-ß2-glycoprotein-I (aβ2GPI) and anti-cardiolipin (aCL) IgG/IgM (group2), 31 for aPS/PT, aβ2GPI and aCL IgG/IgM (group3), 27 for aPS/PT and/or aβ2GPI+aCL IgM at low-titres (group4). 31 healthy donors (HDs) and 24 controls treated with vitamin K antagonists (VKA) were included.
RESULTS
The most deranged TGA and LA profiles were observed in tetra-positive patients (group3) that differed significantly to the other groups, thus those with isolated, double or triple aPL-positivity. Moreover, when comparing the TGA profile of all antiphospholipid syndrome (APS) patients, aPL-carriers, HDs and VKA controls, we observed that the aPL+ patients (especially APS) showed a distinctive profile that allowed to distinguish them from the other groups with significantly higher tLag and tPeak, and lower Peak and area under the curve.When focusing on APS clinical manifestations, patients with a high-risk profile (group3) showed significant differences from those presenting low-titres aPL (group 4) regarding the number of venous events (p=0.04), recurrence of any thrombotic event (p=0.01), of arterial events (5 vs 0, p=0.02), the occurrence of TIA (p=0.04), DVT (p=0.02) and, when analysing extracriteria manifestations, of peripheral artery disease (p=0.04).
CONCLUSIONS
TGA seems a valuable approach to stratify aPL+ patients according to their risk profile. The differences among different populations of autoantibodies specificities could be considered a translational validation of the increased thrombotic risk of patients with triple or tetra aPL-positivity.
目的
在大量抗磷脂抗体（aPL）阳性患者中应用血栓生成分析（TGA）。
材料和方法
对 108 例患者进行 TGA 和狼疮抗凝物（LA）检测，并根据其 aPL 谱进行分组。简要来说，21 例患者抗磷脂酰丝氨酸（aPS）/凝血酶原（PT）IgG/IgM 阳性（组 1），29 例抗β2-糖蛋白 I（aβ2GPI）和抗心磷脂（aCL）IgG/IgM 阳性（组 2），31 例 aPS/PT、aβ2GPI 和 aCL IgG/IgM 阳性（组 3），27 例 aPS/PT 和/或 aβ2GPI+aCL IgM 低滴度阳性（组 4）。纳入 31 例健康供者（HDs）和 24 例接受维生素 K 拮抗剂（VKA）治疗的对照组。
结果
四阳性患者（组 3）的 TGA 和 LA 谱最异常，与其他组有显著差异，因此与孤立、双重或三重 aPL 阳性的患者不同。此外，当比较所有抗磷脂综合征（APS）患者、aPL 携带者、HDs 和 VKA 对照组的 TGA 谱时，我们观察到 aPL+患者（尤其是 APS）表现出独特的谱，可将其与其他组区分开来，其凝血酶时间（tLag）和峰值时间（tPeak）显著升高，峰值和曲线下面积（Area under the curve）显著降低。当关注 APS 临床表现时，高风险谱组（组 3）与低滴度 aPL 组（组 4）相比，静脉事件（p=0.04）、任何血栓事件（p=0.01）、动脉事件（5 比 0，p=0.02）、短暂性脑缺血发作（TIA）（p=0.04）、深静脉血栓形成（DVT）（p=0.02）的发生率存在显著差异，在分析非标准表现时，外周动脉疾病（p=0.04）的发生率也存在显著差异。
结论
TGA 似乎是一种根据患者风险谱对 aPL+患者进行分层的有价值的方法。不同自身抗体特异性人群之间的差异可被视为三联或四联 aPL 阳性患者血栓形成风险增加的转化验证。
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