Coagulation Laboratory, Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University Hospital, Ghent, Belgium.
Blood. 2010 Jan 28;115(4):870-8. doi: 10.1182/blood-2009-09-244426. Epub 2009 Nov 25.
Lupus anticoagulants (LACs) are associated with thromboembolic complications (TECs). LACs can be detected by their anticoagulant properties in thrombin generation assays, by the peak height (PH) and lag time (LT). To assess the thrombotic risk in LAC-positive patients, we have expressed the LAC activity quantitatively by PH/LT calibration curves, constructed for mixtures of monoclonal antibodies against beta2-glycoprotein I (beta2GPI) and prothrombin, spiked in normal plasma. PH/LT was determined in LAC patients, with (n = 38) and without (n = 21) TECs and converted into arbitrary LAC units. LAC titers ranged from 0 to 200 AU/mL, with 5 of 59 patients being negative. In the positive LAC titer population (54 of 59), LAC and anti-beta2GPI immunoglobulin G (IgG) titers correlated with TECs, with odds ratios of 3.54 (95% CI, 1.0-1.7) and 10.0 (95% CI, 1.98-50.6), respectively. In patients with single or combined low titers, useful predictions on thrombosis could be made only after additional measurements of soluble P-selectin and factor VII. This layered strategy yielded positive and negative predictive values, sensitivity, and specificity values approximately 90% in this subgroup. Hence, LAC and anti-beta2GPI IgG titers, when combined with selected markers of the hypercoagulable state, allow a relevant thrombotic risk assessment in nearly all patients with LACs.
狼疮抗凝物 (LAC) 与血栓栓塞并发症 (TEC) 有关。LAC 可以通过其在凝血酶生成测定中的抗凝特性、峰值高度 (PH) 和滞后时间 (LT) 来检测。为了评估 LAC 阳性患者的血栓形成风险，我们通过针对β2-糖蛋白 I (β2GPI) 和凝血酶原的单克隆抗体混合物的 PH/LT 校准曲线，对 LAC 活性进行了定量表达，这些混合物在正常血浆中进行了添加。在有 (n = 38) 和没有 (n = 21) TEC 的 LAC 患者中测定了 PH/LT，并将其转换为任意的 LAC 单位。LAC 滴度范围为 0 至 200 AU/mL，其中 5 名患者为阴性。在阳性 LAC 滴度人群 (54 名患者中的 5 名) 中，LAC 和抗β2GPI 免疫球蛋白 G (IgG) 滴度与 TEC 相关，优势比分别为 3.54(95%CI，1.0-1.7)和 10.0(95%CI，1.98-50.6)。在单一或联合低滴度患者中，仅在额外测量可溶性 P-选择素和因子 VII 后，才能对血栓形成做出有用的预测。在该亚组中，这种分层策略产生了约 90%的阳性和阴性预测值、灵敏度和特异性值。因此，LAC 和抗β2GPI IgG 滴度，当与高凝状态的选定标志物结合使用时，可以对几乎所有 LAC 患者进行相关的血栓形成风险评估。
