Ciraparantag (PER977) is a small-molecule, synthetic, water-soluble broad-spectrum anticoagulant reversal agent. Ciraparantag binds to and neutralizes the anticoagulant activity of unfractionated heparin, low molecular weight heparin, fondaparinux, as well as direct factor Xa inhibitors and direct thrombin inhibitors through non-covalent hydrogen bonding and charge-charge interactions, thereby restoring hemostatic function without exhibiting significant procoagulant effects[1-2]. Ciraparantag is suitable for the management of anticoagulant reversal in patients experiencing severe bleeding or requiring urgent surgery due to anticoagulant therapy[3-4].
In vivo, in an SD rat tail transection bleeding model, a single intravenous injection of Ciraparantag (1.25–31.25mg/kg) was administered either at the reported time of peak concentration (Tmax) of the anticoagulant (pre-injury) or after the injury. The anticoagulants used included oral edoxaban (10mg/kg), oral dabigatran (37.5mg/kg), oral apixaban (3.125mg/kg), oral rivaroxaban (5mg/kg), intravenous unfractionated heparin (1–2.5mg/kg), or intravenous enoxaparin (10mg/kg). Ciraparantag significantly reduced blood loss in the rats[5].
References:
[1] Chan NC, Weitz JI. Ciraparantag as a potential universal anticoagulant reversal agent. Eur Heart J. 2022 Mar 7;43(10):993-995.
[2] Leentjens J, Middeldorp S, Jung C. A short review of ciraparantag in perspective of the currently available anticoagulant reversal agents. Drug Discov Today. 2022 Oct;27(10):103332.
[3] Ansell J, Bakhru S, Laulicht BE, et al. Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects. Eur Heart J. 2022 Mar 7;43(10):985-992.
[4] Siegal DM. Ciraparantag: the next anticoagulant airbag? Blood. 2021 Jan 7;137(1):10-11.
[5] Ansell J, Laulicht BE, Bakhru SH, et al. Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants. Blood. 2021 Jan 7;137(1):115-125.
Ciraparantag (PER977)是一种小分子合成的水溶性广谱抗凝剂逆转剂。Ciraparantag通过非共价氢键和电荷相互作用与普通肝素、低分子量肝素、磺达肝癸钠以及直接Xa因子抑制剂和直接凝血酶抑制剂结合，从而中和其抗凝活性并恢复止血功能，且不表现出明显的促凝血作用[1-2]。Ciraparantag可用于因抗凝药物治疗而发生严重出血或需紧急手术的患者的抗凝逆转管理[3-4]。
在体内，在SD大鼠尾横断出血模型中，单次静脉注射Ciraparantag（1.25–31.25mg/kg）于抗凝剂（口服依度沙班10mg/kg、口服达比加群37.5mg/kg、口服阿哌沙班3.125mg/kg、口服利伐沙班5mg/kg、静脉注射普通肝素1–2.5mg/kg或静脉注射依诺肝素10mg/kg）达峰浓度时（损伤前）或损伤后给药，Ciraparantag能显著减少大鼠的出血量[6]。