Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants

Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants
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DOI:
10.1182/blood-2009-09-244426
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发表时间:
2010-01-28
期刊:
影响因子:
20.3
通讯作者:
Hoylaerts, Marc F.
Hoylaerts, Marc F.
中科院分区:
医学1区
文献类型:
--
作者:
Devreese, Katrien;Peerlinck, Kathelijne;Hoylaerts, Marc F.

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狼疮抗凝剂(LACs)与血栓栓塞并发症(tec)相关。在凝血酶生成试验中,通过峰高(PH)和滞后时间(LT)可以检测到LACs的抗凝特性。为了评估LAC阳性患者的血栓形成风险,我们通过PH/LT校准曲线定量表达LAC活性,该曲线是针对β 2-糖蛋白I (β 2GPI)和凝血酶原的单克隆抗体的混合物,在正常血浆中添加。测定LAC患者(n = 38)和(n = 21)的PH/LT,并转换为任意LAC单位。LAC滴度范围为0 ~ 200 AU/mL, 59例患者中有5例呈阴性。在LAC滴度阳性人群中(59人中有54人),LAC和抗- 2GPI免疫球蛋白G (IgG)滴度与tec相关,比值比分别为3.54 (95% CI, 1.0-1.7)和10.0 (95% CI, 1.98-50.6)。在单个或联合低滴度的患者中,只有在额外测量可溶性p选择素和因子VII后,才能对血栓形成进行有用的预测。这种分层策略在该亚组中产生了阳性和阴性预测值,敏感性和特异性值约为90%。因此,当LAC和抗- 2GPI IgG滴度与高凝状态的选定标记物结合使用时,可以对几乎所有LAC患者进行相关的血栓风险评估。(血。2010;115:870 - 878)
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 beta 2-glycoprotein I (beta 2GPI) 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-beta 2GPI 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-beta 2GPI IgG titers, when combined with selected markers of the hypercoagulable state, allow a relevant thrombotic risk assessment in nearly all patients with LACs. (Blood. 2010;115:870-878)