Cardiovascular Research Institute, 550858Loyola University Chicago, Health Sciences Divisions, Maywood, IL, USA.
Program in Health Science, Universidad Católica de Murcia, Spain.
Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221099934. doi: 10.1177/10760296221099934.
Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage.
UFH and LMWH were studied with andexanet, PS, or saline as potential reversal agents/controls at varying concentrations in ACT, TEG, and anti-Xa and compared to each other.
Andexanet partially neutralized both drugs several TEG parameters at high andexanet concentrations, but it was not as effective as protamine sulfate in any of the assays used. Most TEG parameters were correlated with andexanet concentration. In ACT, significant neutralization was demonstrated at many andexanet concentrations for UFH, but not LMWH. UFH was completely neutralized by PS in ACT, while LMWH was partially neutralized by PS in ACT. Andexanet alfa was a less effective neutralization agent than the protamine sulfate as it only partially neutralized UFH in ACT and was ineffective at neutralizing LMWH when tested at the same concentration as PS (10 ug/mL).
Andexanet partially neutralized UFH and LMWH with variability between assays, necessitating investigation into assay-dependent differences.
Andexanet alfa（andexanet）是一种已批准的解毒剂，用于逆转直接口服抗凝剂（Direct-Xa 制剂）的出血作用，因为它逆转了抗-Xa 活性。未分级肝素（UFH）和低分子量肝素（LMWH）具有抗-Xa 活性。目的是研究由于硫酸鱼精蛋白短缺，andexanet 在激活凝血时间（ACT）、血栓弹力图（TEG）和抗-Xa 中对 UFH 和 LMWH 的中和作用。
在 ACT、TEG 和抗-Xa 中，用 andexanet、PS 或生理盐水作为潜在的逆转剂/对照物，研究 UFH 和 LMWH 在不同浓度下的情况，并相互比较。
在高浓度的 andexanet 下，andexanet 部分中和了这两种药物的几种 TEG 参数，但在所有使用的测定中，其效果不如鱼精蛋白硫酸盐。大多数 TEG 参数与 andexanet 浓度相关。在 ACT 中，在许多 andexanet 浓度下，UFH 表现出明显的中和作用，但 LMWH 则不然。UFH 在 ACT 中被 PS 完全中和，而 LMWH 在 ACT 中被 PS 部分中和。在 ACT 中，andexanet 作为一种中和剂的效果不如鱼精蛋白硫酸盐，因为它只能部分中和 UFH，并且在以与 PS（10ug/mL）相同的浓度测试时，对 LMWH 无效。
andexanet 部分中和了 UFH 和 LMWH，不同的测定方法存在差异，需要进一步研究测定方法的差异。
