Anaerobically stored red blood cells with extended shelf-life

描述(申请人提供)：该项目的长期目标是开发一种新型的血液储存系统，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效率和更低毒性的红细胞。在这个系统中，红细胞在缺氧条件下(厌氧储存)被储存在改良的添加剂溶液中。最终产品将具有更长的保质期(9周或更长时间)，以及更高的疗效和更低的毒性，与传统方法储存的相同年龄的血液相比(更多的活细胞，输血后立即更高的氧气输送能力，以及更多的变形细胞，以更好地进行毛细血管灌流)。新的储存系统在设计上可方便地适应目前的血库运作，而不会对程序或设备造成重大改变。在该项目的第一阶段，使用了一个实验程序来证明厌氧储存的产量；i)在6周的储存后，与传统方法相比，输血后的恢复率明显更高；以及ii)与在传统条件下6周的储存相比，9周的恢复率相当。该第二阶段提案的主要目的是证明，第一阶段中使用的试验性硬件/工艺可以通过制造一个自给自足的、在当前血库环境下容易容纳的血液采集/存储系统而付诸实践，而不会影响其性能。与匹兹堡大学、Filtertek和Multisorb Technologies合作，将在体外设计、制造和测试几个原型存储系统。随后，优化的原型系统将在达特茅斯-希区柯克医学中心的临床试验中进行测试，目的是获得与第一阶段实验程序所获得的结果相当的结果。公共卫生相关性：在过去的几年里，一些科学期刊上发表了一些论文，质疑储存用于输血的红细胞的质量。他们指出：i)较差的临床结果与较多的输血单位有关；ii)输血可能并未导致组织中氧气利用的增加；iii)与输血少于14天的患者相比，术后结果较差的患者接受的血液储存超过14天。建议的厌氧红细胞储存系统提供了更高的输血后活性和不妥协的氧气输送能力，从而在减少输血副作用的同时提高了输血治疗的疗效。在需要长期输血的受试者(如镰状细胞病或β-地中海贫血)中，输注这种红细胞将减少频率和时间平均输血量和总的铁负荷。延长保质期将改善普通血库操作的后勤，缓解周期性的血液短缺，并增加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.