Schlesinger Kimberly W, Ragni Margaret V
Hemophilia Center of Western Pennsylvania, 3636 Boulevard of the Allies, Pittsburgh, PA 15213-4306, USA.
Expert Opin Drug Saf. 2002 Sep;1(3):213-23. doi: 10.1517/14740338.1.3.213.
Haemophilia A and B are X-linked disorders resulting from deficiency of Factor VIII and IX, respectively. Clinical sequellae of Factor VIII or IX deficiency include spontaneous and traumatic haemorrhages into joints, soft tissues, and muscles. The cornerstone of therapy has been replacement of the deficient factor, historically with pooled-plasma derivatives. The unfortunate blood-borne infection transmission (such as HIV, hepatitis B and C viruses), inhibitor formation, immunosuppression, and, in certain cases, thrombosis by these products has spawned major advances and innovations in the manufacture of clotting products. Recombinant technology has virtually eliminated transmissible disease risk; yet, the presence of albumin in second and third generation recombinant products raises, at the least, theoretical risk of prions and parvovirus B19. Other non-infectious complications, including inhibitor formation, allergic reactions, and thrombosis, remain formidable concerns. Despite this, recombinant factors remain the most attractive treatment approach for haemophilia. Future improvement awaits the development of safe and effective gene transfer technology.
甲型和乙型血友病是分别由因子 VIII 和因子 IX 缺乏引起的 X 连锁疾病。因子 VIII 或因子 IX 缺乏的临床后遗症包括关节、软组织和肌肉的自发性和创伤性出血。治疗的基石一直是补充缺乏的因子，历史上使用的是混合血浆衍生物。这些产品不幸导致了血源性感染传播（如 HIV、乙型和丙型肝炎病毒）、抑制剂形成、免疫抑制，以及在某些情况下的血栓形成，这催生了凝血产品制造方面的重大进展和创新。重组技术几乎消除了传染病风险；然而，第二代和第三代重组产品中白蛋白的存在至少带来了朊病毒和细小病毒 B19 的理论风险。其他非感染性并发症，包括抑制剂形成、过敏反应和血栓形成，仍然是令人担忧的重大问题。尽管如此，重组因子仍然是血友病最具吸引力的治疗方法。未来的改进有待安全有效的基因转移技术的发展。
