Nishimura Susumu, Ishida Tadao, Imai Kohzoh
First Department of Internal Medicine, Sapporo Medical University.
Nihon Rinsho. 2002 Mar;60(3):525-30.
Monoclonal antibody therapies have conducted to not only hematologic malignancies but also disorders of hemostasis and coagulation. This article describes the recent advances of monoclonal antibody therapy for bleeding disorders such as idiopathic thrombocytopenic purpura(ITP), hemophilia A, disseminated intravascular coagulation(DIC), and thrombosis. Rituximab, chimeric anti-CD20 monoclonal antibody treatment has a valuable effect in the patients with ITP, and clinical trials using anti-CD40 ligand monoclonal antibody for ITP are underway. Anti-CD40 ligand monoclonal antibody can be an alternative therapy for hemophilia A patients with inhibitors to factor VIII. In thrombosis, anti-tissue factor monoclonal antibody and anti-factor IX(a) monoclonal antibody were established as novel anticoagulant regents. Plasminogen activator inhibitor-1(PAI-1) increases in endotoxin-induced DIC and many thrombotic diseases such as myocardial infarction, type 2 diabetes mellitus, and hyperlipidemia. Anti-PAI-1 monoclonal antibody reduced fibrin deposition in DIC mouse model. Treatment of these monoclonal antibodies for the molecules regulating coagulation-fibrinolysis system may be utilized for acute coronary syndrome and venous thrombosis.
单克隆抗体疗法不仅应用于血液系统恶性肿瘤，还应用于止血和凝血障碍。本文介绍了单克隆抗体疗法在治疗诸如特发性血小板减少性紫癜（ITP）、甲型血友病、弥散性血管内凝血（DIC）和血栓形成等出血性疾病方面的最新进展。利妥昔单抗，即嵌合抗CD20单克隆抗体治疗对ITP患者有显著疗效，针对ITP使用抗CD40配体单克隆抗体的临床试验正在进行中。抗CD40配体单克隆抗体可作为有抗凝血因子VIII抑制剂的甲型血友病患者的替代疗法。在血栓形成方面，抗组织因子单克隆抗体和抗因子IX(a)单克隆抗体已被确立为新型抗凝剂。纤溶酶原激活物抑制剂-1（PAI-1）在内毒素诱导的DIC以及许多血栓性疾病如心肌梗死、2型糖尿病和高脂血症中会升高。抗PAI-1单克隆抗体可减少DIC小鼠模型中的纤维蛋白沉积。针对调节凝血-纤溶系统的分子使用这些单克隆抗体进行治疗可能适用于急性冠状动脉综合征和静脉血栓形成。
