PDF(Pubmed)
Abstract：
Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.
摘要：
系统性硬化症是一种罕见的疾病，死亡率很高。它是一种多系统结缔组织疾病，由于内皮自身免疫激活以及组织和血管纤维化，诱发血管病变，血管生成浪费。内皮损伤引起血小板活化和免疫细胞粘附。内皮细胞的脱离导致暴露的内下层中存在的血小板和胶原的相互作用。这激发了几种凝固因子的激活，通过凝血酶生成诱导促血栓形成的情况，将纤维蛋白原转化为纤维蛋白。此外，凝血酶还有其他功能,如诱导平滑肌细胞和成纤维细胞增生，从而有利于纤维化。在系统性硬化症中发现静脉血栓栓塞的风险增加，而肺动脉高压可能是由于小肺动脉阻塞所致。也可能发生肺静脉闭塞性疾病。华法林的结果不一致,而随机的结果，阿哌沙班与安慰剂的安慰剂对照临床试验仍在等待中.正在开发一种基于抗XI因子药物的新的抗凝策略，目的是实现最佳的抗凝治疗，同时降低出血风险。这一类研究的分子类型包括单克隆抗体，小分子,天然抑制剂,反义寡核苷酸,和适体。患有系统性硬化症的患者可能是计划分析这些分子的功效和安全性的临床试验的理想候选人。
