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肝素发现于1916年,作为抗凝剂使用只50多年。肝素治疗的并发症有出血、过敏反应、骨质疏松、肝素相关性血小板减小症及血栓栓塞。1976年Johoson等首先发现志愿者皮下注射低分子肝素(LMWH)时,在血浆中产生的抗活化因子X(抗-X_a),其活性比高分子肝素(HMWH)的抗-X_a活性高。同年,Andersson等报告体外实验用部分凝血活酶生成时间(APTT)和凝血酶时间(TT)测定肝素的抗凝活性,发现LMWH抗凝活性较低,但用抗-X_a测定其抗凝活却性相当高。1978年Lane等也证实了上述发现。本文复习文献对LMWH的抗凝特性、药物动力学和临床应用的研究近况作一综合介绍。
Heparin was discovered in 1916 and only used as anticoagulant for more than 50 years. Heparin treatment complications are bleeding, allergic reactions, osteoporosis, heparin-related thrombocytopenia and thromboembolism. In 1976, when Johoson et al first found that LMWH was subcutaneously injected into volunteers, the anti-activator X (anti-X_a) produced in plasma was more active than the anti-X_a of HMWH. In the same year, Andersson et al reported in vitro experiments using partial thromboplastin time (APTT) and thrombin time (TT) determination of anticoagulant activity of heparin and found LMWH anticoagulant activity was lower, but with anti-X_a determination of anticoagulant activity Sex is quite high. Lane Lane 1978 also confirmed the above findings. This review article on LMWH anticoagulant properties, pharmacokinetics and clinical application of the current situation for a comprehensive introduction.