Walenga J M, Michal K, Hoppensteadt D, Wood J J, Robinson J A, Bick R L
Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Clin Appl Thromb Hemost. 1999 Oct;5 Suppl 1:S76-84.
Antibody-mediated disorders of heparin-induced thrombocytopenia and antiphospholipid antibody syndrome have remarkably similar clinical presentations, both of which can progressively result in severe vascular and thrombotic disorders. We hypothesized that the mechanism of platelet activation as occurs in heparin-induced thrombocytopenia may also occur in antiphospholipid antibody syndrome particularly at the vascular wall, that endothelial injury may be similar in heparin-induced thrombocytopenia and antiphospholipid antibody syndrome, and that these alterations may be caused by related antibodies. Antibody titers and vascular endothelial damage in patients with heparin-induced thrombocytopenia and antiphospholipid antibody syndrome were studied in plasma samples collected from normals (n = 17), heparin-induced thrombocytopenia patients (n = 15), antiphospholipid antibody syndrome patients (n = 30), and patients clinically diagnosed with antiphospholipid antibody syndrome and heparin-induced thrombocytopenia (n = 8). Diagnosis of heparin-induced thrombocytopenia was confirmed by 14C-serotonin release assay or positive antiheparin-platelet factor 4 antibody titer, and antiphospholipid antibody syndrome was confirmed by positive anti-beta 2-glycoprotein (GP) 1/cardiolipin (IgG or IgM) antibody titer. The antiheparin-platelet factor 4 antibody was not detected in any patient with antiphospholipid antibody syndrome. Patients with heparin-induced thrombocytopenia did not have elevated IgG anti-beta 2-GP1 titers, but three (20%) patients had low-positive IgM anti-beta 2-GP1 titers. The endothelial damage markers of soluble thrombomodulin, soluble P-selectin (p < 0.05 vs. normal), plasminogen activator inhibitor-1 and tissue factor were elevated in heparin-induced thrombocytopenia and antiphospholipid antibody syndrome patients. The soluble E-selectin was elevated only in the patients with both heparin-induced thrombocytopenia and antiphospholipid antibody syndrome (p < 0.05 vs. normal). Levels of soluble L-selectin and von Willebrand factor were not different from normals. The pathogenesis of heparin-induced thrombocytopenia and antiphospholipid antibody syndrome appears to be due to two distinct antibodies but associated with similar damage to the vascular endothelium in both diseases.
抗体介导的肝素诱导的血小板减少症和抗磷脂抗体综合征具有非常相似的临床表现，两者都可逐渐导致严重的血管和血栓形成性疾病。我们推测，肝素诱导的血小板减少症中发生的血小板活化机制也可能发生在抗磷脂抗体综合征中，特别是在血管壁，肝素诱导的血小板减少症和抗磷脂抗体综合征中的内皮损伤可能相似，并且这些改变可能由相关抗体引起。我们研究了从正常人（n = 17）、肝素诱导的血小板减少症患者（n = 15）、抗磷脂抗体综合征患者（n = 30）以及临床诊断为抗磷脂抗体综合征和肝素诱导的血小板减少症的患者（n = 8）采集的血浆样本中肝素诱导的血小板减少症和抗磷脂抗体综合征患者的抗体滴度和血管内皮损伤情况。肝素诱导的血小板减少症通过14C - 5 -羟色胺释放试验或抗肝素 - 血小板因子4抗体滴度阳性得以确诊，抗磷脂抗体综合征通过抗β2 - 糖蛋白（GP）1/心磷脂（IgG或IgM）抗体滴度阳性得以确诊。在任何抗磷脂抗体综合征患者中均未检测到抗肝素 - 血小板因子4抗体。肝素诱导的血小板减少症患者的IgG抗β2 - GP1滴度并未升高，但有3名（20%）患者的IgM抗β2 - GP1滴度呈低阳性。可溶性血栓调节蛋白、可溶性P - 选择素（与正常相比，p < 0.05）、纤溶酶原激活物抑制剂 - 1和组织因子等内皮损伤标志物在肝素诱导的血小板减少症和抗磷脂抗体综合征患者中均升高。可溶性E - 选择素仅在同时患有肝素诱导的血小板减少症和抗磷脂抗体综合征的患者中升高（与正常相比，p < 0.05）。可溶性L - 选择素和血管性血友病因子水平与正常人无差异。肝素诱导的血小板减少症和抗磷脂抗体综合征的发病机制似乎归因于两种不同的抗体，但在这两种疾病中均与对血管内皮的相似损伤有关。
