Thrombocytopenia (TCP) may cause severe and life-threatening bleeding. While this may be prevented by platelet transfusions, transfusions are associated with potential complications, do not always work (platelet refractory) and are not always available. There is an urgent need for a synthetic alternative. We evaluated the ability of fibrinogen-coated nanospheres (FCNs) to prevent TCP-related bleeding. FCNs are made of human albumin polymerized into a 100-nm sphere and coated with fibrinogen. We hypothesized that FCNs would bind to platelets through fibrinogen-GPIIb/IIIa interactions, contributing to hemostasis in the setting of TCP. We used two murine models to test these effects: in the first model, BALB/c mice received 7.25 Gy total-body irradiation (TBI); in the second model, lower dose TBI (7.0 Gy) was combined with an anti-platelet antibody (anti-CD41) to induce severe TCP. Deaths in both models were due to gastrointestinal or intracranial bleeding. Addition of antiplatelet antibody to 7.0 Gy TBI significantly worsened TCP and increased mortality compared to 7.0 Gy TBI alone. FCNs significantly improved survival compared to saline control in both models, suggesting it ameliorated TCP-related bleeding. Additionally, in a saphenous vein bleeding model of antibody-induced TCP, FCNs shortened bleeding times. There were no clinical or histological findings of thrombosis or laboratory findings of disseminated intravascular coagulation after FCN treatment. In support of safety, fluorescence microscopy suggests that FCNs bind to platelets only upon platelet activation with collagen, limiting activity to areas of endothelial damage. To our knowledge, this is the first biosynthetic agent to demonstrate a survival advantage in TCP-related bleeding.

血小板减少症 (TCP) 可能导致严重且危及生命的出血。虽然这可以通过血小板输注来预防，但输血与潜在的并发症有关，并不总是有效（血小板难治性）并且并不总是可用的。迫切需要一种合成替代品。我们评估了纤维蛋白原涂层纳米球 (FCN) 预防 TCP 相关出血的能力。FCN 由人白蛋白聚合成 100 纳米球体并涂有纤维蛋白原制成。我们假设 FCN 会通过纤维蛋白原-GPIIb/IIIa 相互作用与血小板结合，有助于 TCP 的止血。我们使用两个小鼠模型来测试这些效果：在第一个模型中，BALB/c 小鼠接受了 7.25 Gy 的全身照射 (TBI)；在第二种模型中，较低剂量的 TBI (7. 0 Gy) 与抗血小板抗体 (anti-CD41) 结合以诱导严重 TCP。两种模型的死亡都是由于胃肠道或颅内出血。与单独使用 7.0 Gy TBI 相比，在 7.0 Gy TBI 中添加抗血小板抗体会显着恶化 TCP 并增加死亡率。与两种模型中的盐水对照相比，FCN 显着提高了存活率，表明它改善了 TCP 相关的出血。此外，在抗体诱导 TCP 的大隐静脉出血模型中，FCN 缩短了出血时间。FCN 治疗后没有血栓形成的临床或组织学发现或弥散性血管内凝血的实验室发现。为了支持安全性，荧光显微镜表明 FCNs 仅在血小板被胶原蛋白激活时才与血小板结合，从而限制了内皮损伤区域的活性。