Asztabski Michal, Wypasek Ewa, Ząbczyk Michał, Undas Anetta
John Paul II Hospital, Krakow, Poland.
John Paul II Hospital, Krakow, Poland; Institute of Cardiology Jagiellonian University Medical College, Krakow, Poland.
Thromb Res. 2014 Nov;134(5):945-51. doi: 10.1016/j.thromres.2014.07.042. Epub 2014 Aug 21.
Formation of denser fibrin networks displaying impaired lysability has been reported in subjects at an increased risk of atherosclerosis. Given recent data on prothrombotic fibrin clot phenotype reported in patients with antiphospholipid syndrome (APS), we tested the hypothesis that altered fibrin clot properties are associated with increased intima-media thickness (IMT) observed in PAPS.
We studied 30 consecutive patients with PAPS and 30 controls matched for age, sex and the type of previous thromboembolism. We assessed plasma fibrin clot permeability (Ks) and clot lysis time (CLT) with their potential determinants. The IMT was measured in 3 segments of the carotid arteries.
Patients with APS had 15.2% lower Ks (p=0.002) and 9.7% prolonged CLT (p=0.039) compared with controls. The IMT in the APS group was greater in the common carotid artery (5.7%; p=0.002), at the bifurcation (17.46%; p<0.001), and the internal artery (9.26%; p=0.015). Patients with triple positivity in the antiphospholipid antibody profile (n=9; 30%) had lower Ks and greater IMT (both, p<0.05), compared with those with single positivity (n=13; 43.3%). Multivariate analysis adjusted for potential confounders showed that in APS patients, oxidized low-density lipoproteins (p=0.019) were the only independent predictor of Ks, while thrombin activatable fibrinolysis inhibitor activity (p<0.001) predicted CLT. Plasminogen activator inhibitor-1 (PAI-1) was found to be the independent predictor of the IMT in the common carotid artery (p=0.004), and in the internal carotid artery (p<0.001).
Reduced Ks and susceptibility to lysis are associated with greater IMT in PAPS, which might contribute to the early atherosclerosis in this disease.
据报道,在动脉粥样硬化风险增加的受试者中,会形成溶解能力受损的更致密纤维蛋白网络。鉴于近期关于抗磷脂综合征(APS)患者血栓前纤维蛋白凝块表型的数据,我们检验了以下假设:纤维蛋白凝块特性的改变与原发性抗磷脂综合征(PAPS)患者中观察到的内膜中层厚度(IMT)增加有关。
我们研究了30例连续的PAPS患者以及30例在年龄、性别和既往血栓栓塞类型方面相匹配的对照者。我们评估了血浆纤维蛋白凝块通透性(Ks)和凝块溶解时间(CLT)及其潜在决定因素。在颈动脉的3个节段测量IMT。
与对照组相比,APS患者的Ks降低了15.2%(p = 0.002),CLT延长了9.7%(p = 0.039)。APS组的IMT在颈总动脉更大(5.7%;p = 0.002),在分叉处更大(17.46%;p < 0.001),在内侧动脉更大(9.26%;p = 0.015)。抗磷脂抗体谱呈三联阳性的患者(n = 9;30%)与呈单阳性的患者(n = 13;43.3%)相比,Ks更低且IMT更大(两者均p < 0.05)。针对潜在混杂因素进行调整的多变量分析显示,在APS患者中,氧化型低密度脂蛋白(p = 0.019)是Ks的唯一独立预测因子,而凝血酶激活的纤维蛋白溶解抑制剂活性(p < 0.001)可预测CLT。纤溶酶原激活物抑制剂-1(PAI-1)被发现是颈总动脉(p = 0.004)和颈内动脉(p < 0.001)IMT的独立预测因子。
Ks降低和对溶解的易感性降低与PAPS患者更大的IMT相关,这可能导致该疾病早期动脉粥样硬化。