School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia.
Lupus. 2011 Dec;20(14):1474-83. doi: 10.1177/0961203311418267. Epub 2011 Oct 12.
Thrombosis is a frequent manifestation in patients with systemic lupus erythematosus (SLE), although precise mechanisms remain unclear. This study investigated whether the major physiological trigger of blood coagulation, the tissue factor (TF) pathway, was altered in SLE patients. Furthermore, we investigated potential associations between the TF pathway, the presence of antiphospholipid (APL) antibodies and other abnormalities present in SLE. A total of 101 participants (40 SLE patients and 61 age- and sex-matched controls) were recruited from Tasmania, Australia. Markers of the TF pathway, hypercoagulability, inflammation and endothelial cell damage were measured in plasma. Serum levels of APL antibodies (anti-cardiolipin antibodies [ACL], lupus anticoagulants [LAC], anti-beta2-glycoprotein-1 [anti-β2GP1] and anti-prothrombin antibodies) were also determined. Despite similar TF and TF pathway inhibitor (TFPI) total antigen levels, SLE patients had significantly increased levels of TFPI free antigen (patients vs controls; mean ± SD) (11.6 ± 0.9 ng/mL vs 6.4 ± 0.4 ng/mL; p < 0.001) but significantly reduced TFPI activity (0.66 ± 0.07 U/mL vs 1.22 ± 0.03 U/mL; p < 0.001), compared with healthy controls. Anti-TFPI activity, designated as the ability of isolated IgG fractions to inhibit TFPI activity in normal plasma, was detected in 19/40 (47.5%) of SLE patients and 3/40 (7.5%) of healthy controls. The significant reduction in TFPI activity in SLE patients reflects impaired functional control of the TF pathway. Moreover, SLE patients with a history of thrombosis demonstrated higher levels of TFPI activity compared with patients without a previous thrombotic event (0.97 ± 0.07 U/mL vs 0.53 ± 0.14 U/mL; p = 0.0026). Changes to the TF pathway were not associated with manifestations of SLE such as inflammation or endothelial cell damage. The results from this study suggest hypercoagulability in SLE may (in part) be due to reduced TFPI activity, a mechanism that appears to be independent of other abnormalities in SLE.
血栓形成是系统性红斑狼疮（SLE）患者的常见表现，尽管确切机制尚不清楚。本研究旨在探讨凝血的主要生理触发因素——组织因子（TF）途径是否在 SLE 患者中发生改变。此外，我们还研究了 TF 途径、抗磷脂（APL）抗体的存在以及 SLE 中存在的其他异常之间的潜在关联。本研究共招募了 101 名参与者（40 名 SLE 患者和 61 名年龄和性别匹配的对照者），来自澳大利亚塔斯马尼亚州。在血浆中测量了 TF 途径标志物、高凝状态、炎症和血管内皮细胞损伤。还测定了血清 APL 抗体（抗心磷脂抗体[ACL]、狼疮抗凝物[LAC]、抗β2-糖蛋白 1[抗-β2GP1]和抗凝血酶原抗体）水平。尽管 SLE 患者的 TF 和 TF 途径抑制剂（TFPI）总抗原水平相似，但与健康对照组相比，SLE 患者的 TFPI 游离抗原水平显著升高（患者 vs 对照组；平均值 ± SD）（11.6 ± 0.9ng/mL vs 6.4 ± 0.4ng/mL；p<0.001），而 TFPI 活性显著降低（0.66 ± 0.07 U/mL vs 1.22 ± 0.03 U/mL；p<0.001）。在 19/40（47.5%）名 SLE 患者和 3/40（7.5%）名健康对照者中检测到抗 TFPI 活性，该活性被定义为分离的 IgG 部分在正常血浆中抑制 TFPI 活性的能力。SLE 患者 TFPI 活性的显著降低反映了 TF 途径功能控制受损。此外，有血栓形成史的 SLE 患者的 TFPI 活性水平高于无先前血栓事件的患者（0.97 ± 0.07 U/mL vs 0.53 ± 0.14 U/mL；p=0.0026）。TF 途径的改变与 SLE 的表现（如炎症或血管内皮细胞损伤）无关。本研究结果表明，SLE 的高凝状态可能部分是由于 TFPI 活性降低所致，这种机制似乎独立于 SLE 中的其他异常。
