pRBC Contaminant Removal with Hemocompatible Porous Polymer Beads

浓缩红细胞（pRBC）输血可以挽救生命。然而，成千上万的非溶血性 输血反应在世界范围内每年都有发生，从轻微的发热和肠炎到严重的生命危险， 威胁性反应，如重度高钾血症、过敏反应和输血相关急性肺损伤 （TRALI）。轻度-中度反应会导致患者不适、记录和检测成本， 严重的反应可能导致昂贵的重症监护，患者受伤，甚至死亡， 医疗保健利用率和成本。目前，还没有简单的解决方案来净化污染物， 这些反应来自pRBC。因此，CytoSorbents正在开发HemoDefend-RBC™，一种易于使用， 在线过滤器，去除细胞外钾（K+）和广谱的其他物质， 可能对输血受者造成潜在伤害的pRBC，包括游离血红蛋白、生物活性脂质， 细胞因子、反应酶和抗体。这些污染物要么是来自 供体血液，或在血液储存过程中由于RBC变质和溶血而产生。 过量K+引起的高钾血症在需要大量输血的患者中尤其危险。 由于创伤和高风险手术、肾功能不全患者以及儿科患者的pRBC单位 患者在美国，目前唯一可用的解决这些污染物的方法是清洗单元 鲜血然而，这需要相当多的时间、物流和费用。HemoDefend-RBC设计用于 通过重力流过滤pRBC，不需要额外的设备或能源。过滤是 与当前输血实践兼容，包括任何标准抗凝剂和添加剂 解决方案货架稳定的器械由惰性材料制成，不含易腐或可沥滤的生物 组件，并且可以容易地进行伽马灭菌。 HemoDefend-RBC过滤器利用并扩展了CytoSorbents专有的吸附性多孔聚合物 用于医疗过滤的微珠技术平台。我们美国监管战略的最初重点是 HemoDefend-RBC将批准用于从pRBC中去除细胞外K+的输血点过滤器 单位，以降低输血相关高钾血症的风险。钾可以达到 由于细胞表面离子泵和溶血的失调， 导致K+从红细胞中释放出来。拟议的IIB期桥梁计划提供资金， 来自公司的配套资金，用于额外的研究，临床开发和制造 扩大活动规模，推动美国和欧盟监管批准和国际商业化 HemoDefend-RBC。HemoDefend-RBC过滤器的可用性将提供易于使用、低成本 解决方案，以安全和有效地“洗血”的污染物范围广泛，没有费用， 物流和目前物理清洗血液所需的时间。

Packed red blood cell (pRBC) transfusions save lives. However, hundreds of thousands of non-hemolytic transfusion reactions occur each year worldwide, ranging from mild fever and pruritis, to serious life- threatening reactions such as severe hyperkalemia, anaphylaxis, and transfusion-related acute lung injury (TRALI). Mild-moderate reactions drive patient discomfort, documentation, and testing costs while serious reactions can result in expensive intensive care, patient injury, and even death, driving increased healthcare utilization and cost. Currently, there is no easy solution to purify contaminants that cause these reactions from pRBCs. Therefore, CytoSorbents is developing HemoDefend-RBC™, an easy-to-use, in-line filter, that removes extracellular potassium (K+) plus a broad spectrum of other substances from pRBCs that may potentially harm transfusion recipients, including free hemoglobin, bioactive lipids, cytokines, reactive enzymes, and antibodies. These contaminants are either residual components from donor blood, or are generated during blood storage due to RBC deterioration and hemolysis. Hyperkalemia from excessive K+ is particularly a risk in patients requiring transfusion of large numbers of pRBC units due to trauma and high-risk surgery, those with renal insufficiency, as well as in pediatric patients. In the U.S., the only currently available means to address these contaminants is to wash units of blood. However, this takes considerable time, logistics and expense. HemoDefend-RBC is designed to filter pRBCs via gravity flow and requires no additional equipment or energy source. Filtration is compatible with current transfusion practices, including any of the standard anti-coagulants and additive solutions. The shelf-stable device is made of inert materials with no perishable or leachable biological components and can be readily gamma-sterilized. The HemoDefend-RBC filter leverages and extends CytoSorbents’ proprietary adsorptive porous polymer bead technology platform for medical filtration. The initial focus of our U.S. regulatory strategy for HemoDefend-RBC will be the approval of a point-of-transfusion filter to remove extracellular K+ from pRBC units in order to reduce the risk of transfusion-associated hyperkalemia. Potassium can reach extremely high levels during cold storage due to the dysregulation of cell surface ion pumps and hemolysis that causes K+ to be released from red cells. The proposed Phase IIB bridge program provides funding, with matching funds from the company, for additional research, clinical development, and manufacturing scale-up activities, to drive U.S. and E.U. regulatory approval and international commercialization of HemoDefend-RBC. Availability of the HemoDefend-RBC filter will provide an easy-to-use, low cost solution to safely and effectively “wash blood” of a broad range of contaminants without the expense, logistics, and time currently required to physically wash blood.