Farrugia Albert, Robert Patrick
Blood and Tissue Unit, Office of Devices, Blood and Tissues, Therapeutic Goods Administration, P.O. Box 100, Woden, ACT 2606, Australia.
Best Pract Res Clin Haematol. 2006;19(1):243-58. doi: 10.1016/j.beha.2005.01.002.
Although early developments in immunology and haemostasis indicated the potential therapeutic application of plasma fractions, it was not until Cohn's development of a stable plasma protein solution for the treatment of battlefield injuries in the Second World War that the manufacture of plasma derivatives became part of industrial pharmaceutics. The resulting albumin product remained the mainstay of the plasma fractionation industry for the next 40 years but the sequential removal of 'unwanted' fractions en route to the final albumin product lent itself to the characterization and use of other products. By the 1970s, the harvesting of cryoprecipitate before the initiation of the Cohn fractionation scheme allowed access to products for treating the haemophilias, using simple precipitation and, from the 1970s, chromatographic methods to concentrate the coagulation factors. Further minor modifications allowed the administration of the immunoglobulin in high intravenous dosages, significantly extending the usage and indications of immunoglobulin products. By the 1980s, the needs for haemophilia A had made factor VIII, rather than albumin, the driver for plasma fractionation, and the advent of recombinant coagulation factors in the 1990s contributed to immunoglobulin assuming the position of the plasma procurement driver. In recent years, the plasma industry has developed a relatively large range of products but has also entered a period of consolidation as various pressures, such as technological innovations, infectious and other risks and quality requirements-all of which are discussed in this review-decreased the demand of at least two of the three products that underpin the industry's current financial basis. At the same time, modern principles of evidence-based therapeutics are coming into play in the traditionally empirical base for most of the usage for plasma derivatives. The future use of plasma derivatives, at least in the developed world, will probably follow a different path to the one seen so far, and a sound understanding for the pathophysiology of the medical indications for plasma therapies should contribute to a continuing role for these medicines in modern therapeutics.
尽管免疫学和止血学的早期发展显示了血浆成分潜在的治疗应用，但直到二战期间科恩开发出用于治疗战场创伤的稳定血浆蛋白溶液，血浆衍生物的生产才成为工业制药的一部分。由此产生的白蛋白产品在接下来的40年里一直是血浆分离行业的支柱，但在最终白蛋白产品生产过程中对“不需要的”成分的依次去除，为其他产品的特性鉴定和使用提供了可能。到20世纪70年代，在科恩分级分离方案开始前收集冷沉淀，使得通过简单沉淀以及从20世纪70年代起采用色谱方法浓缩凝血因子来获得治疗血友病的产品成为可能。进一步的微小改进使得能够高剂量静脉注射免疫球蛋白，显著扩大了免疫球蛋白产品的用途和适应证。到20世纪80年代，甲型血友病的需求使凝血因子VIII而非白蛋白成为血浆分离的驱动力，而20世纪90年代重组凝血因子的出现促使免疫球蛋白成为血浆采购的驱动力。近年来，血浆行业开发了种类相对繁多的产品，但也进入了一个整合期，因为各种压力，如技术创新、感染及其他风险和质量要求（所有这些将在本综述中讨论），降低了支撑该行业当前财务基础的三种产品中至少两种的需求。与此同时，循证治疗的现代原则正在传统上基于经验的血浆衍生物多数用途中发挥作用。血浆衍生物的未来使用，至少在发达国家，可能会遵循一条与迄今为止不同的道路，而对血浆疗法医学适应证病理生理学的深入理解应有助于这些药物在现代治疗中继续发挥作用。
