Arai M
Department of Laboratory Medicine, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023
Rinsho Byori. 2001 Oct;49(10):1000-4.
During the course of replacement therapy, 22-30% of patients with severe hemophilia A develop alloantibody to factor VIII. Autoantibodies to coagulation factors rarely occur in elder individuals with previously normal hemostatic mechanisms or in patients with various underlying disorders. Although the great majority of the acquired inhibitors are directed to factor VIII, the antibodies may arise to every coagulation factor. The inhibitor antibodies directly inactivate specific clotting factor, or occasionally, they bind to a nonfunctional site, resulting in increased plasma clearance. In the last decade, we experienced 12 hemophilia A and 3 hemophilia B patients who developed factor VIII and factor VIII and factor IX inhibitor, respectively, 9 patients with autoantibody to factor VIII (acquired hemophilia), and 4 patients with acquired von Willebrand syndrome. Among 12 factor VIII inhibitors, 4 patients were identified to have inversion in the factor VIII gene, 1 with 4 bases deletion, and 1 with missense mutation resulting in G479R. Four of 9 patients with acquired hemophilia had underlying disorders of autoimmune hemolytic anemia, macroglobulinemia, urticaria, and pharyngeal cancer at the development of factor VIII inhibitor. Antibody to von willebrand factor was detected in 3 of 4 patients with acquired von Willebrand syndrome.
在替代治疗过程中，22%至30%的重度甲型血友病患者会产生针对凝血因子VIII的同种抗体。在既往止血机制正常的老年个体或患有各种基础疾病的患者中，很少会出现针对凝血因子的自身抗体。尽管绝大多数获得性抑制剂是针对凝血因子VIII的，但这些抗体也可能针对每一种凝血因子产生。抑制剂抗体直接使特定凝血因子失活，或者偶尔它们会结合到一个无功能的位点，导致血浆清除率增加。在过去十年中，我们诊治了12例甲型血友病患者和3例乙型血友病患者，他们分别产生了针对凝血因子VIII和凝血因子IX的抑制剂，9例针对凝血因子VIII的自身抗体患者（获得性血友病），以及4例获得性血管性血友病综合征患者。在12例凝血因子VIII抑制剂患者中，4例被鉴定出凝血因子VIII基因存在倒置，1例有4个碱基缺失，1例有导致G479R的错义突变。9例获得性血友病患者中有4例在出现凝血因子VIII抑制剂时患有自身免疫性溶血性贫血、巨球蛋白血症、荨麻疹和咽喉癌等基础疾病。4例获得性血管性血友病综合征患者中有3例检测到针对血管性血友病因子的抗体。
