pRBC Contaminant Removal with Hemocompatible Porous Polymer Beads

浓缩红细胞 (pRBC) 输注可挽救生命。然而，数十万非溶血患者 全世界每年都会发生输血反应，从轻微发烧和瘙痒到严重的生命危险 威胁性反应，例如严重高钾血症、过敏反应和输血相关的急性肺损伤 （特拉利）。轻度至中度反应会导致患者不适、文件记录和测试成本增加，同时 严重反应可能导致昂贵的重症监护、患者受伤甚至死亡，驾驶增加 医疗保健利用率和成本。目前，没有简单的解决方案来净化导致污染的污染物 这些反应来自 pRBC。因此，CytoSorbents 正在开发 HemoDefend-RBC™，这是一种易于使用的、 在线过滤器，可去除细胞外钾 (K) 以及多种其他物质 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 供血者的血液，或在血液储存过程中由于红细胞变质和溶血而产生的。 对于需要输注大量钾的患者来说，过量钾引起的高钾血症尤其危险。 由于外伤和高风险手术、肾功能不全者以及儿科患者而导致的 pRBC 单位 患者。在美国，目前解决这些污染物的唯一可用方法是清洗设备 的血。然而，这需要大量的时间、物流和费用。 HemoDefend-RBC 旨在 通过重力流过滤 pRBC，无需额外的设备或能源。过滤是 与当前的输血实践兼容，包括任何标准抗凝剂和添加剂 解决方案。该耐储存装置由惰性材料制成，不含易腐烂或可浸出的生物物质。 组件，并且可以轻松进行伽马射线灭菌。 HemoDefend-RBC 过滤器利用并扩展了 CytoSorbents 专有的吸附性多孔聚合物 用于医疗过滤的珠子技术平台。我们美国监管策略的最初重点 HemoDefend-RBC 将获得批准用于去除 pRBC 中细胞外 K 的输血点过滤器 单位，以降低输血相关高钾血症的风险。钾含量可以达到极高 由于细胞表面离子泵失调和溶血，冷藏期间含量较高 导致红细胞释放 K。拟议的 IIB 阶段过渡计划提供资金， 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 过滤器的推出将提供一种易于使用、低成本的解决方案 安全有效地“清洗血液”中各种污染物的解决方案，无需花费任何费用， 物流，以及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.