A novel agent to manage thrombocytopenic patients with platelet transfusion refractoriness

项目总结 血小板输注不耐受(PTR)或未能达到预期的血小板水平 血小板输注阻碍了对血小板减少患者出血事件的处理。PTR 病情与严重出血并发症的高风险和存活率降低有关， 住院时间和更高的住院费用。现有的管理战略是基于 长时间获得的去白细胞产品、人类白细胞抗原匹配的血小板或交叉匹配的血小板 和昂贵的程序。由血小板生成素模拟物或重组因子XIII组成的替代品 没有显示出降低死亡率的能力。纤维板公司提出了一种新的止血方法 对于发生PTR的血小板减少患者，在静脉注射纤维素板-S(FPS)的基础上， 一种即用的纤维蛋白原包衣白蛋白纳米球悬浮液。FPS可显著减少出血 与临床前放射性血小板减少相关的时间和总存活率的提高 啮齿动物模型通过在伤口处与剩余激活的血小板形成共聚集体 血管内皮细胞。各种临床前研究表明，FPS是安全的，但不是 引发血管内凝血。值得注意的是，FPS并没有隔离在脾中，而且FPS是特异的 在给人注射后，还没有检测到抗体。这些特点，连同它的 止血能力支持FPS在免疫状态下处理血小板减少患者中的应用 和非免疫性PTR。然而，它们的有效性和安全性还需要在血小板减少性临床前试验中得到验证。 在PTR条件下的模型。NIH SBIR第一阶段的目的是研究1)FPS在降低 临床前建立的血小板减少和PTR(TPTR)(双)模型的出血参数 兔和ii)拟议方法的安全性。通过提供有效的治疗，纤维盘有望 减少出血并发症，改善和提高PTR患者的存活率。

PROJECT SUMMARY Platelet Transfusion Refractoriness (PTR) or the failure to achieve the desired level of blood platelets after platelet transfusion, hampers the management of bleeding episodes in thrombocytopenic patients. PTR condition is associated with a high risk of severe bleeding complications and reduced survival rate, longer hospital stays and higher hospital costs. Existing management strategies are based on the transfusion of leukodepleted products, HLA-matched platelets, or cross-matched platelets which are obtained after lengthy and expensive procedures. Alternatives consisting of thrombopoietin mimetics, or recombinant factor XIII have not shown the ability to reduce mortality. Fibroplate is proposing a new approach to manage bleeding in thrombocytopenic patients who develop PTR, based on the intravenous injection of Fibrinoplate-S (FPS), a ready-to-use suspension of fibrinogen-coated albumin nanospheres. FPS significantly reduces the bleeding time and improves overall survival rate associated with radiation-induced thrombocytopenia in preclinical rodent models through the formation of co-aggregates with the residual activated platelets at wound sites on the endothelium of the blood vessel. Various preclinical studies demonstrated that FPS is safe and does not induce intravascular coagulation. Remarkably, FPS is not sequestered in the spleen, and FPS specific antibodies have not been detected after its administration in humans. These characteristics, together with its hemostatic capacity support the use of FPS in the management of thrombocytopenic patients with immune and non-immune PTR. However, their efficacy and safety need validation in a thrombocytopenic preclinical model under PTR conditions. This NIH SBIR Phase I aims at investigating i) the efficacy of FPS in reducing bleeding parameters in an established (double) model of thrombocytopenia and PTR (TPTR) preclinically in rabbits and ii) the safety of the proposed approach. By offering effective treatment, Fibroplate is expected to reduce bleeding complications and improve and promote survival in thrombocytopenic patients with PTR.