Anaerobically stored red blood cells with extended shelf-life

描述（由申请人提供）：该项目的长期目标是开发一种新的血液储存系统，该系统将延长添加剂系统红细胞单位的保质期，同时为输血治疗提供更高疗效和更低毒性的红细胞。在该系统中，红细胞在缺氧条件下（厌氧储存）储存在改性添加剂溶液中。与传统方法储存的相同年龄的血液相比，最终产品将具有更长的保质期（9周或更长）以及更高的功效和更低的毒性（更有活力的细胞，在输血后立即具有更高的氧气输送能力，以及更多可变形的细胞，以便更好地进行毛细血管灌注）。新的存储系统的设计很容易适应目前的血库操作，而不会引起程序或设备的重大改变。在该项目的第一阶段，采用了一个实验程序来证明厌氧储存的产量；1)与传统方法相比，6周后输血后恢复显著提高；ii)与常规条件下6周的储存量相比，9周的回收率相当。本第二阶段提案的主要目的是证明第一阶段使用的实验硬件/过程可以通过制造一个独立的血液采集/存储系统而简化为实践，该系统可以在当前血库设置下轻松适应，而不会影响其性能。与匹兹堡大学、Filtertek和Multisorb Technologies合作，将设计、制造和测试几种原型存储系统。随后，一个优化的原型系统将在达特茅斯-希区柯克医疗中心进行临床试验，目标是获得与第一阶段实验过程中获得的结果相当的结果。公共卫生相关性：在过去几年中，科学期刊上出现了许多论文，质疑储存用于输血的红细胞的质量。他们指出；1)较差的临床结果与较高的输血单位数相关；Ii)输血可能没有引起组织中氧利用的增加；iii)与接受少于14天血液的患者相比，接受超过14天血液的患者术后预后更差。提出的厌氧红细胞储存系统提供了更高的输血后活力和不受损害的氧输送能力，从而提高了输血治疗的疗效，同时减少了输血的副作用。这种红细胞的输血将减少需要长期输血的受试者（如镰状细胞病或-地中海贫血）的平均输血次数和时间以及总铁负荷。延长保质期将改善一般血库操作的后勤保障，缓解周期性血液短缺，提高术前自体献血的效用。

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop a novel blood storage system that will extend the shelf life of additive system red cell units, and at the same time, deliver red cells of higher efficacy and lower toxicity for transfusion therapy. In this system, red cells are stored in a modified additive solution under oxygen-depleted condition (anaerobic storage). The final product will have extended shelf life (9 weeks or more) as well as higher efficacy and lower toxicity compared to same-aged blood stored by conventional methods (more viable cells, higher oxygen delivery capacity immediately after transfusion and more deformable cells for better capillary perfusion). The new storage system is design to be readily accommodated by the current blood banking operation without incurring major alteration in procedures or equipments. In the Phase I of this project, an experimental procedure was used to demonstrated that anaerobic storage yields; i) a significantly higher post- transfusion recovery compared to the conventional method after 6 weeks of storage; and ii) a comparable 9-week recovery compared to 6-week storage under conventional conditions. The main aim of this Phase II proposal is to demonstrate that an experimental hardware/ processes used in the Phase I can be reduced to practice by fabricating a blood collection/storage system that is self-contained and easily accommodated under current blood bank settings without compromises in its performances. In partnership with University of Pittsburgh, Filtertek and Multisorb Technologies, several prototypes storage system will be designed, fabricated and tested in vitro. Subsequently, an optimized prototype system will be tested in a clinical trial at Dartmouth- Hitchcock Medical Center with a goal of obtaining results comparable to ones attained under experimental procedure in the Phase I. PUBLIC HEALTH RELEVANCE: In the past several years, a number of papers have appeared in scientific journals questioning the quality of red blood cells stored for transfusion. They indicated that; i) worse clinical outcomes were associated with higher number of units transfused; ii) blood transfusion may not have induced increased oxygen utilization in tissues; and iii) worse post-operative outcomes were associated with patients receiving blood stored for longer than 14 days compared with patients receiving less than 14-day old blood. Proposed anaerobic red blood cell storage system delivers higher post- transfusion viability and uncompromised oxygen delivery capacity, thereby improving the efficacy of transfusion therapy while reducing side effects of transfusion. Transfusion of such red cells will reduce the frequency- and time- averaged blood transfusion volume and total iron burden in subjects who require chronic transfusion (e.g., sickle cell disease or beta-thalassemia). Extended shelf life will improve the logistics of general blood bank operations, alleviate the periodic blood shortages, and increase the utility of pre-operative autologous blood donation.