Studies on Tissue Factor Pathway Inhibitor Antigen Release by Bovine, Ovine and Porcine Heparins Following Intravenous Administration to Non-Human Primates.
Studies on Tissue Factor Pathway Inhibitor Antigen Release by Bovine, Ovine and Porcine Heparins Following Intravenous Administration to Non-Human Primates.
复制标题
DOI：
10.1177/1076029620951851
复制
发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Fareed J
中科院分区：
文献类型：
--
作者：
Kouta A;Hoppensteadt D;Bontekoe E;Jeske W;Duff R;Cera L;Fareed J
普通肝素（UFH）是一种硫酸化糖胺聚糖，由含有艾杜糖醛酸（或葡萄糖醛酸）和葡糖胺的重复二糖组成，具有不同的硫酸化程度。UFH释放组织因子途径抑制物（TFPI），其通过灭活因子Xa和因子VIIa/TF复合物来抑制凝血的外源性途径。临床上使用的大多数肝素来源于猪肠粘膜，然而，肝素也可以来源于牛和绵羊来源的组织。目前，由于猪肝素被广泛用于生产低分子量肝素（LMWH），因此存在一些关于猪肝素短缺的担忧。此外，由于一些国家的文化和宗教原因，需要肝素的替代来源。目前正在开发牛粘膜肝素（BMH），以重新引入美国市场，用于医疗和手术适应症。与猪粘膜肝素（PMH）相比，BMH显示出稍弱的抗凝活性。在这项研究中，我们确定了TFPI抗原水平后，管理的各种剂量的UFH从不同的来源。这些研究表明，IV给予非人灵长类动物等重剂量的PMH和绵羊粘膜肝素（OMH）导致相当的TFPI抗原从内皮细胞释放。此外，TFPI水平显著高于BMH给药后观察到的TFPI抗原水平。效价调整给药导致所有3种肝素的TFPI释放曲线相当。因此，这种给药可以为UFH的胃肠外适应症提供统一的抗凝水平。这些观察结果保证了在特定适应症中的进一步临床验证。
Unfractionated heparin (UFH) is a sulfated glycosaminoglycan that consists of repeating disaccharides, containing iduronic acid (or glucuronic acid) and glucosamine, exhibiting variable degrees of sulfation. UFHs release tissue factor pathway inhibitor (TFPI) which inhibits the extrinsic pathway of coagulation by inactivating factor Xa and the factor VIIa/TF complex. Most heparins used clinically are derived from porcine intestinal mucosa however, heparins can also be derived from tissues of bovine and ovine origin. Currently there are some concerns about the shortage of the porcine heparins as they are widely used in the manufacturing of the low molecular weight heparins (LMWHs). Moreover, due to cultural and religious reasons in some countries, alternative sources of heparins are needed. Bovine mucosal heparins (BMH) are currently being developed for re-introduction to the US market for both medical and surgical indications. Compared to porcine mucosal heparin (PMH), BMH exhibits a somewhat weaker anti-coagulant activity. In this study, we determined the TFPI antigen level following administration of various dosages of UFHs from different origins. These studies demonstrated that IV administration of equigravemetric dosages of PMH and ovine mucosal heparin (OMH) to non-human primates resulted in comparable TFPI antigen release from endothelial cells. In addition, the levels of TFPI were significantly higher than TFPI antigen levels observed after BMH administration. Potency adjusted dosing resulted in comparable TFPI release profiles for all 3 heparins. Therefore, such dosing may provide uniform levels of anticoagulation for the parenteral indications for UFHs. These observations warrant further clinical validation in specific indications.
登录
查看更多内容
猪，牛和卵巢肝素的稳定同位素分析。
影响因子：
3.8
作者：
Jasper, John P.;Zhang, Fuming;Poe, Russell B.;Linhardt, Robert J.
通讯作者：
Linhardt, Robert J.
影响因子：
6.5
作者：
Hansen, JB;Sandset, PM;Bendz, B
通讯作者：
Bendz, B
影响因子：
7.5
作者：
HOPPENSTEADT, DA;WALENGA, JM;FAREED, J
通讯作者：
FAREED, J
影响因子：
2.9
作者：
Kouta, Ahmed;Jeske, Walter;Fareed, Jawed
通讯作者：
Fareed, Jawed
DOI：
10.1111/jth.12188
发表时间：
2013-05
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Maroney SA;Ellery PE;Wood JP;Ferrel JP;Martinez ND;Mast AE
通讯作者：
Mast AE