A novel agent to manage thrombocytopenic patients with platelet transfusion refractoriness

项目摘要 血小板输注不应性（PTR）或输注后未能达到所需的血小板水平 血小板输注阻碍了血小板减少症患者出血事件的处理。PTR 这种情况与严重出血并发症的高风险和生存率降低有关， 住院时间和更高的住院费用。现有的管理战略是基于 经过长时间的去除白细胞的产品、HLA匹配的血小板或交叉匹配的血小板 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。Fibroplate提出了一种新的方法来管理出血 在发生PTR的血小板减少症患者中，基于静脉注射Fibrinoplate-S（FPS）， 即用型纤维蛋白原包被的白蛋白纳米球悬浮液。FPS显著减少出血 临床前研究中与放射诱导的血小板减少症相关的时间和总生存率的提高 通过在伤口部位与残留的活化血小板形成共聚集体， 血管的内皮各种临床前研究表明，FPS是安全的， 引起血管内凝血。值得注意的是，FPS不是隔离在脾脏中，FPS特异性 在人类中施用后未检测到抗体。这些特点，以及 止血能力支持FPS用于免疫性血小板减少症患者的管理 和非免疫PTR。然而，它们的有效性和安全性需要在血小板减少的临床前研究中进行验证。 PTR条件下的模型。该NIH SBIR I期旨在研究i）FPS在降低 血小板减少症和PTR（TPTR）的已建立（双重）模型中的出血参数， （1）安全性;（2）安全性。通过提供有效的治疗，Fibroplate有望 减少出血并发症，改善和提高PTR患者的生存率。

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.