National Heart and Lung Institute, Imperial College London, London, UK.
Department of Haematology, Royal Brompton and Imperial College Healthcare NHS Trust and Imperial College London, London, UK.
J Clin Lipidol. 2019 Sep-Oct;13(5):788-796. doi: 10.1016/j.jacl.2019.06.009. Epub 2019 Jul 2.
Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis.
The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a).
In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays.
Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham.
Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.
升高的脂蛋白（a）[Lp(a)]是难治性心绞痛患者常见的心血管危险因素。Lp(a)的载脂蛋白（a）成分与纤溶酶原具有结构同源性，可增强血栓形成并损害纤维蛋白溶解。
本研究旨在评估脂蛋白吸附术对高 Lp(a)患者血栓形成和纤维蛋白溶解标志物的影响。
在一项前瞻性、单盲、交叉试验中，将 20 名难治性心绞痛和 Lp(a)升高>50mg/dL的患者随机分为三组，分别接受为期三个月的每周脂蛋白吸附术或假治疗。在吸附术/假治疗前后采集的血液使用全球血栓形成试验进行评估，以评估体外血栓形成（闭塞时间）和内源性纤维蛋白溶解（溶解时间）所需的时间，以及血管性血友病因子、纤维蛋白原、D-二聚体、凝血酶/抗凝血酶 III 复合物、凝血酶原片段 1+2 和凝血酶生成试验。
与假治疗相比，脂蛋白吸附术可显著降低 Lp(a)水平（100.2[四分位距{IQR}，69.6143.0] vs 24.8[17.2，34.0]mg/dL，P=0.0001），但假治疗无显著变化（P=0.0001）。吸附术延长了闭塞时间（576±116 s vs 723±142 s，P<0.0001），反映了血小板反应性降低，同时溶解时间延长（1340[1128，1682] s vs 847[685，1302] s，P=0.0006），反映了纤维蛋白溶解增强，而假治疗无此变化。吸附术可降低血管性血友病因子（149[89.0，164] vs 64.2[48.5，89.8]IU/dL，P=0.0001）和纤维蛋白原（3.12±0.68 vs 2.20±0.53g/L，P<0.0001）水平，同时增加凝血酶原片段 1+2 水平（158.16[128.77，232.09] vs 795.12[272.55，1201.00]pmol/L，P=0.0006）。吸附术或假治疗对 D-二聚体、凝血酶/抗凝血酶 III 复合物或凝血酶生成试验无影响。
脂蛋白吸附术可降低难治性心绞痛患者的 Lp(a)水平，并改善部分血栓形成和纤维蛋白溶解参数。
