Fakiha Siddiqui, Debra Hoppensteadt, Walter Jeske, Eduardo Ramacciotti, Alfonso Tafur, Jawed Fareed
{"title":"Andexanet Alfa 几乎能像硫酸原胺一样中和牛源、牛源和猪源非减量肝素的抗凝作用","authors":"Fakiha Siddiqui, Debra Hoppensteadt, Walter Jeske, Eduardo Ramacciotti, Alfonso Tafur, Jawed Fareed","doi":"10.1177/10760296241247558","DOIUrl":null,"url":null,"abstract":"IntroductionAndexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO<jats:sub>4</jats:sub>) is frequently used to neutralize UFH. This study aimed to investigate the comparative neutralization profiles of AA and PrSO<jats:sub>4</jats:sub> for heparins of bovine, ovine, and porcine origin.Materials and MethodsThe neutralization effect of PrSO<jats:sub>4</jats:sub> at 25 µg/ml and AA at 100 µg/ml was studied on an approximate surgical/interventional concentration of heparin by supplementing whole blood with each of the heparins at 25 µg/ml. For the clotting profile (activated partial thromboplastin time: aPTT), amidolytic (anti-Xa and anti-IIa), and thrombin generation assay each of the heparin were supplemented from –10–0.62 µg/ml.ResultsIn the whole blood ACT studies, all three heparins produced strong anti-coagulant effects (400–450 seconds) compared to saline (130–150 seconds). Both AA and PrSO<jats:sub>4</jats:sub> almost fully neutralized the anti-coagulant effects of heparins (140–160 seconds). Both antidotes completely reversed the anticoagulant effects of all three heparins in the aPTT and thrombin generation assay. However, PrSO<jats:sub>4</jats:sub> was more effective in neutralizing the anti-Xa, and anti-IIa effects than AA, which only partially neutralized these effects.ConclusionAndexanet alfa at 100 µg/ml effectively neutralizes the therapeutic and surgical/interventional concentrations of heparins in in-vitro settings. While differences in the anti-Xa, and anti-IIa effects between heparins were noted, anti-coagulant effect of these agents in the aPTT assay were comparable. A similar neutralization profile was observed in the ACT and thrombin generation assays by both agents.","PeriodicalId":10335,"journal":{"name":"Clinical and Applied Thrombosis/Hemostasis","volume":"9 1","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Andexanet Alfa Neutralizes the Anticoagulant Effects of Unfractionated Heparin of Bovine, Ovine and Porcine Origin Almost as Protamine Sulfate\",\"authors\":\"Fakiha Siddiqui, Debra Hoppensteadt, Walter Jeske, Eduardo Ramacciotti, Alfonso Tafur, Jawed Fareed\",\"doi\":\"10.1177/10760296241247558\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"IntroductionAndexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO<jats:sub>4</jats:sub>) is frequently used to neutralize UFH. This study aimed to investigate the comparative neutralization profiles of AA and PrSO<jats:sub>4</jats:sub> for heparins of bovine, ovine, and porcine origin.Materials and MethodsThe neutralization effect of PrSO<jats:sub>4</jats:sub> at 25 µg/ml and AA at 100 µg/ml was studied on an approximate surgical/interventional concentration of heparin by supplementing whole blood with each of the heparins at 25 µg/ml. For the clotting profile (activated partial thromboplastin time: aPTT), amidolytic (anti-Xa and anti-IIa), and thrombin generation assay each of the heparin were supplemented from –10–0.62 µg/ml.ResultsIn the whole blood ACT studies, all three heparins produced strong anti-coagulant effects (400–450 seconds) compared to saline (130–150 seconds). Both AA and PrSO<jats:sub>4</jats:sub> almost fully neutralized the anti-coagulant effects of heparins (140–160 seconds). Both antidotes completely reversed the anticoagulant effects of all three heparins in the aPTT and thrombin generation assay. However, PrSO<jats:sub>4</jats:sub> was more effective in neutralizing the anti-Xa, and anti-IIa effects than AA, which only partially neutralized these effects.ConclusionAndexanet alfa at 100 µg/ml effectively neutralizes the therapeutic and surgical/interventional concentrations of heparins in in-vitro settings. While differences in the anti-Xa, and anti-IIa effects between heparins were noted, anti-coagulant effect of these agents in the aPTT assay were comparable. A similar neutralization profile was observed in the ACT and thrombin generation assays by both agents.\",\"PeriodicalId\":10335,\"journal\":{\"name\":\"Clinical and Applied Thrombosis/Hemostasis\",\"volume\":\"9 1\",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Applied Thrombosis/Hemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/10760296241247558\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Applied Thrombosis/Hemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10760296241247558","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
导言:重组凝血因子 Xa 安非他酮(AA)是一种已获批准的口服 Xa 抑制剂(阿哌沙班和利伐沙班)的解毒剂。非分叶肝素(UFH)常用于治疗、介入和手术适应症。硫酸原胺(PrSO4)常用于中和 UFH。本研究旨在调查 AA 和 PrSO4 对牛源、绵羊源和猪源肝素的中和效果比较。材料和方法通过在全血中补充 25 µg/ml 的肝素,研究了 25 µg/ml 的 PrSO4 和 100 µg/ml 的 AA 对近似手术/介入浓度肝素的中和效果。结果在全血 ACT 研究中,与生理盐水(130-150 秒)相比,所有三种肝素都产生了很强的抗凝效果(400-450 秒)。AA 和 PrSO4 几乎完全中和了肝素的抗凝作用(140-160 秒)。在 aPTT 和凝血酶生成试验中,两种解毒剂都能完全逆转所有三种肝素的抗凝作用。然而,PrSO4 在中和抗 Xa 和抗 IIa 作用方面比 AA 更有效,后者只能部分中和这些作用。虽然不同肝素的抗 Xa 和抗 IIa 作用存在差异,但这些药物在 aPTT 试验中的抗凝效果相当。在 ACT 和凝血酶生成试验中,两种药物的中和效果相似。
Andexanet Alfa Neutralizes the Anticoagulant Effects of Unfractionated Heparin of Bovine, Ovine and Porcine Origin Almost as Protamine Sulfate
IntroductionAndexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO4) is frequently used to neutralize UFH. This study aimed to investigate the comparative neutralization profiles of AA and PrSO4 for heparins of bovine, ovine, and porcine origin.Materials and MethodsThe neutralization effect of PrSO4 at 25 µg/ml and AA at 100 µg/ml was studied on an approximate surgical/interventional concentration of heparin by supplementing whole blood with each of the heparins at 25 µg/ml. For the clotting profile (activated partial thromboplastin time: aPTT), amidolytic (anti-Xa and anti-IIa), and thrombin generation assay each of the heparin were supplemented from –10–0.62 µg/ml.ResultsIn the whole blood ACT studies, all three heparins produced strong anti-coagulant effects (400–450 seconds) compared to saline (130–150 seconds). Both AA and PrSO4 almost fully neutralized the anti-coagulant effects of heparins (140–160 seconds). Both antidotes completely reversed the anticoagulant effects of all three heparins in the aPTT and thrombin generation assay. However, PrSO4 was more effective in neutralizing the anti-Xa, and anti-IIa effects than AA, which only partially neutralized these effects.ConclusionAndexanet alfa at 100 µg/ml effectively neutralizes the therapeutic and surgical/interventional concentrations of heparins in in-vitro settings. While differences in the anti-Xa, and anti-IIa effects between heparins were noted, anti-coagulant effect of these agents in the aPTT assay were comparable. A similar neutralization profile was observed in the ACT and thrombin generation assays by both agents.
期刊介绍:
CATH is a peer-reviewed bi-monthly journal that addresses the practical clinical and laboratory issues involved in managing bleeding and clotting disorders, especially those related to thrombosis, hemostasis, and vascular disorders. CATH covers clinical trials, studies on etiology, pathophysiology, diagnosis and treatment of thrombohemorrhagic disorders.