Bizzaro N, Ghirardello A, Zampieri S, Iaccarino L, Tozzoli R, Ruffatti A, Villalta D, Tonutti E, Doria A
Laboratory of Clinical Pathology, Hospital of Tolmezzo, Tolmezzo, Italy.
J Thromb Haemost. 2007 Jun;5(6):1158-64. doi: 10.1111/j.1538-7836.2007.02532.x.
To evaluate the role of anti-prothrombin (anti-PT) antibodies in predicting thrombosis in patients with systemic lupus erythematosus (SLE).
An inception cohort of 101 SLE patients (12 males, 89 females; mean age 30 +/- 8 years), was considered. Clinical and laboratory evaluations were regularly performed during a 15-year follow-up (median 108 months) with a special focus on thromboembolic events. Serum samples were collected at time of diagnosis and at least once a year thereafter. IgG and IgM anti-PT, anti-cardiolipin (aCL) and anti-beta(2)glycoprotein I (beta(2)GPI) antibodies were measured by enzyme-linked immunosorbent assay (ELISA); lupus anticoagulant (LAC) was assayed by the dilute Russell's viper venom time and activated partial thromboplastin time tests. The analytical specificity of anti-PT ELISA was investigated. The timing of thrombosis occurrence was calculated using the Kaplan-Meier method.
In the 15-year follow-up, thrombosis occurred in 14 out of the 101 patients: venous thrombosis in nine cases and arterial thrombosis in five. IgG and/or IgM anti-PT, anti-beta(2)GPI and aCL antibodies, and LAC activity were detected in ten, nine, seven, and nine cases, with sensitivity for thrombosis of 71.4%, 64.3%, 50% and 64.3%, respectively. Thrombosis-free survival was 90% at 5 years and 85.8% at 10 and 15 years, respectively. Thrombosis was predicted by anti-PT (P = 0.001), anti-beta(2)GPI antibodies (P = 0.002) and LAC activity (P = 0.001). Moreover, the risk of thrombosis progressively increased with the number of positive antiphospholipid antibody tests. The presence of four positive antibody tests was associated with a risk of thrombosis thirtyfold higher than in their absence.
This longitudinal study shows that IgG anti-PT antibodies are predictors of thrombosis in SLE patients.
评估抗凝血酶原(抗 - PT)抗体在预测系统性红斑狼疮(SLE)患者血栓形成中的作用。
纳入101例SLE患者(12例男性,89例女性;平均年龄30±8岁)的起始队列。在15年随访期间(中位随访时间108个月)定期进行临床和实验室评估,特别关注血栓栓塞事件。在诊断时及此后每年至少采集一次血清样本。采用酶联免疫吸附测定(ELISA)检测IgG和IgM抗 - PT、抗心磷脂(aCL)和抗β2糖蛋白I(β2GPI)抗体;采用稀释蝰蛇毒时间和活化部分凝血活酶时间试验检测狼疮抗凝物(LAC)。研究抗 - PT ELISA的分析特异性。采用Kaplan - Meier法计算血栓形成的时间。
在15年随访中,101例患者中有14例发生血栓形成:9例为静脉血栓形成,5例为动脉血栓形成。10例、9例、7例和9例分别检测到IgG和/或IgM抗 - PT、抗β2GPI和aCL抗体以及LAC活性,对血栓形成的敏感性分别为71.4%、64.3%、50%和64.3%。5年、10年和15年无血栓生存率分别为90%、85.8%和85.8%。抗 - PT(P = 0.001)、抗β2GPI抗体(P = 0.002)和LAC活性(P = 0.001)可预测血栓形成。此外,血栓形成风险随抗磷脂抗体检测阳性数量的增加而逐渐增加。四项抗体检测呈阳性与无阳性时相比,血栓形成风险高30倍。
这项纵向研究表明,IgG抗 - PT抗体是SLE患者血栓形成的预测指标。