Impaired contraction of blood clots as a novel prothrombotic mechanism in systemic lupus erythematosus
Impaired contraction of blood clots as a novel prothrombotic mechanism in systemic lupus erythematosus
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DOI：
10.1042/cs20171510
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发表时间：
2018-01-31
期刊：
影响因子：
6
通讯作者：
Litvinov, Rustem I.
中科院分区：
文献类型：
--
作者：
Giang Le Minh;Peshkova, Alina D.;Litvinov, Rustem I.
这项工作的目的是研究血栓收缩/回缩在系统性红斑狼疮(SLE)血栓并发症中的可能作用。使用一种新的自动化方法，我们研究了51名SLE患者和60名健康献血员血液中凝块收缩的动力学。用流式细胞仪通过P-选择素的表达和纤维蛋白原结合能力来评估SLE患者的血小板功能。SLE患者的血栓收缩速度和程度明显低于正常人，尤其是抗dsDNA抗体水平较高的患者。从SLE患者血液中分离的血小板对凝血酶受体激活肽刺激的部分不反应与血小板收缩能力降低有关。为了测试抗dsDNA自身抗体是否导致持续的血小板激活，随后导致细胞衰竭和功能障碍，我们在凝血前将来自SLE患者的纯化的外源性抗dsDNA自身抗体加入到正常血液中。为了支持这一假设，抗体首先增强凝块收缩，然后以一种时间依赖的方式抑制它。重要的是，血栓收缩参数与疾病严重程度的直接相关性表明，血管内血栓和血栓的致密性降低可能是SLE的一个致病因素，可能会夸大血栓形成部位受损的血流。综上所述，SLE自身抗体可影响血小板的收缩能力，导致血栓和血栓体积缩小的能力降低，从而增加血管阻塞，并可能加重SLE血栓并发症的病程和转归。
The aim of this work was to examine a possible role of clot contraction/retraction in thrombotic complications of systemic lupus erythematosus (SLE). Using a novel automated method, we investigated kinetics of clot contraction in the blood of 51 SLE patients and 60 healthy donors. The functionality of platelets in the SLE patients was assessed using flow cytometry by expression of P-selectin and fibrinogen-binding capacity. The rate and degree of clot contraction were significantly reduced in SLE patients compared with healthy subjects, especially in the patients with higher blood levels of anti-dsDNA antibodies. The reduced platelet contractility correlated with partial refractoriness of platelets isolated from the blood of SLE patients to stimulation induced by the thrombin receptor activating peptide. To test if the anti-dsDNA autoantibodies cause continuous platelet activation, followed by exhaustion and dysfunction of the cells, we added purified exogenous anti-dsDNA autoantibodies from SLE patients to normal blood before clotting. In support of this hypothesis, the antibodies first enhanced clot contraction and then suppressed it in a time-dependent manner. Importantly, a direct correlation of clot contraction parameters with the disease severity suggests that the reduced compactness of intravascular clots and thrombi could be a pathogenic factor in SLE that may exaggerate the impaired blood flow at the site of thrombosis. In conclusion, autoantibodies in SLE can affect platelet contractility, resulting in reduced ability of clots and thrombi to shrink in volume, which increases vessel obstruction and may aggravate the course and outcomes of thrombotic complications in SLE.