Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Thromb Res. 2011 Oct;128(4):e9-13. doi: 10.1016/j.thromres.2011.03.021. Epub 2011 Apr 14.
Heparin is widely used for anticoagulation, often requiring the subsequent administration of a reversal agent. The only approved reversal agent for heparin is protamine sulfate, which induces well described adverse reactions in patients. Previously we reported a novel class of heparin antagonists based on the bacteriophage Qβ platform, displaying polyvalent cationic motifs which bind with high affinity to heparin. Here we report heparin reversal by the most effective of these virus-like particles (VLP) in samples from patients who were administered heparin during cardiac procedures or therapeutically for treatment of various thrombotic conditions. The VLP consistently reversed heparin in these samples, including those from patients that received high doses of heparin, with greater efficiency than a negative control VLP and with significantly less variability than protamine sulfate. These results provide the first step towards validation of heparin antagonist VLPs as viable alternatives to protamine.
肝素被广泛用于抗凝，通常需要随后使用逆转剂。肝素唯一批准的逆转剂是硫酸鱼精蛋白，它会在患者中引起描述明确的不良反应。我们之前报道了基于噬菌体 Qβ平台的新型肝素拮抗剂，这些拮抗剂具有多价阳离子基序，可与肝素高亲和力结合。在这里，我们报告了在接受心脏手术或治疗各种血栓形成疾病期间给予肝素的患者样本中，这些病毒样颗粒（VLP）中最有效的一种逆转肝素的情况。VLP 在这些样本中一致地逆转了肝素，包括那些接受高剂量肝素的患者，其效率高于阴性对照 VLP，且变异性明显低于硫酸鱼精蛋白。这些结果为验证肝素拮抗剂 VLP 作为鱼精蛋白的可行替代品迈出了第一步。
