Messmore H L, Coyne E, Wehrmacher W H, Demir A M, Fareed J
Department of Medicine, Loyola University Medical Center, IL, USA.
Curr Pharm Des. 2004;10(9):1001-10. doi: 10.2174/1381612043452802.
The use of heparin for the prophylaxis and treatment of venous and arterial thrombosis had been the standard of care for clinicians until 1982. At that time the introduction of depolymerized heparin for the prophylaxis of deep vein thrombosis in surgical patients was introduced. A number of such products, low molecular weight heparins (LMWH) were patented and introduced as new drugs during the ensuing of 20 years. Each LMWH had to be given a clinical trial against standard heparin for the several thromboembolic disorders for which heparin was the standard of care. By definition LMWH had to have unequal factor Xa and IIa inhibitor potency, expressed as a Xa-IIa ratio of greater than 1. They also had a molecular weight reduction to about one third that of heparin. A major advantage of LMWH over heparin was the subcutaneous route of injection for treatment of thrombotic disorders in contrast to the intravenous route for heparin. They had greater bioavailability than heparin by the subcutaneous route, a longer half-life and better predictability of dose response. It was found that routine laboratory monitoring was unnecessary. When given a trial against heparin, LMWH was equally safe and effective for most venous and arterial disorders. A new synthetic version of (pentasaccharide) both heparin and LMWH has been at least if not more effective than one LMWH (enoxaparin).
直到1982年，肝素用于预防和治疗静脉及动脉血栓形成一直是临床医生的治疗标准。当时，低聚肝素被引入用于预防外科手术患者的深静脉血栓形成。在随后的20年里，许多此类产品，即低分子量肝素（LMWH）获得专利并作为新药推出。每种低分子量肝素都必须针对肝素作为治疗标准的几种血栓栓塞性疾病与标准肝素进行临床试验。根据定义，低分子量肝素必须具有不等的Xa和IIa抑制效力，以大于1的Xa-IIa比值表示。它们的分子量也降至肝素的约三分之一。与肝素相比，低分子量肝素的一个主要优点是治疗血栓性疾病采用皮下注射途径，而肝素采用静脉注射途径。通过皮下途径，它们比肝素具有更高的生物利用度、更长的半衰期和更好的剂量反应可预测性。人们发现无需进行常规实验室监测。当与肝素进行对比试验时，低分子量肝素对大多数静脉和动脉疾病同样安全有效。一种新的合成版（五糖）肝素和低分子量肝素至少与一种低分子量肝素（依诺肝素）一样有效，如果不是更有效的话。
