Systems Biology and Medicine Center for Complex Diseases, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Medical Records, Affiliated Hospital of Qingdao University, Qingdao, China.
Prog Mol Biol Transl Sci. 2019;163:21-39. doi: 10.1016/bs.pmbts.2019.02.003. Epub 2019 Mar 25.
Heparin is an anticoagulant medication that was discovered in 1917 and used in clinic since 1935. Low molecular weight heparins (LMWHs) represent a refined use of heparin as anticoagulant medications that were developed in 1980s. LMWHs are obtained by cleaving heparin with different chemical or enzymatic methods. Eight chemically distinct and officially approved LMWHs are Bemiparin, Certoparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, and Tinzaparin. LMWHs are mainly used for preventing blood clots, for treating deep vein thrombosis and pulmonary embolism, and for treating myocardial infarction. LMWHs have advantages over heparin in that they can be used at home with good predictability, dose-dependent plasma levels, a long half-life, less bleeding for a given antithrombotic even, smaller risk of osteoporosis in long-term use, and smaller risk of heparin-induced thrombocytopenia and thrombosis, a potential side effect of heparin. However, heparin is reversible with protamine sulfate while LMWHs have no antidote. Moreover, LMWHs have less of an effect on inhibiting thrombin activity than heparin. Furthermore, patients with end-stage renal diseases have to use heparin because LMWHs are dependent on functioning kidney for their clearance but heparin is primarily cleared in the liver. We will review the recent progress made on the clinically approved and under clinical trialed LMWHs and their potential medical applications. In particular, we will provide an update on the chemical characteristics and clinical use of different branded LMWHs. In addition, the potential clinical applications of LMWHs in other therapeutic area will also be discussed.
肝素是一种抗凝药物，于 1917 年发现，1935 年开始在临床上使用。低分子量肝素（LMWH）是 20 世纪 80 年代开发的一种改良的肝素抗凝药物。LMWH 通过用不同的化学或酶方法裂解肝素而获得。有 8 种化学上不同且经官方批准的 LMWH，分别为贝米肝素、亭扎肝素、达肝素、依诺肝素、那屈肝素、那法肝素、瑞肝素和替扎肝素。LMWH 主要用于预防血栓形成、治疗深静脉血栓形成和肺栓塞以及治疗心肌梗死。LMWH 相对于肝素具有以下优势：可以在家中使用，具有良好的可预测性、剂量依赖性的血浆水平、较长的半衰期、在给定的抗血栓形成剂量下出血较少、长期使用时骨质疏松症的风险较小、肝素诱导的血小板减少症和血栓形成的风险较小，肝素是一种潜在的副作用。然而，肝素可以用硫酸鱼精蛋白逆转，而 LMWH 没有解毒剂。此外，LMWH 对抑制凝血酶活性的作用比肝素小。此外，终末期肾病患者必须使用肝素，因为 LMWH 依赖于功能正常的肾脏清除，而肝素主要在肝脏中清除。我们将回顾最近在临床上批准和临床试验中的 LMWH 及其潜在的医学应用方面取得的进展。特别是，我们将提供不同品牌的 LMWH 的化学特性和临床应用的最新信息。此外，还将讨论 LMWH 在其他治疗领域的潜在临床应用。
