Acostamadiedo J M, Iyer U G, Owen J
Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Expert Opin Pharmacother. 2000 May;1(4):803-14. doi: 10.1517/14656566.1.4.803.
Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan antithrombotic agent approved for the prophylaxis of post-operative deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. Danaparoid is a low molecular weight heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic activity has been well established. Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT). It has excellent bioavailability following s.c. injection. Danaparoid has little effect on routine coagulation tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]). Patients with elevated serum creatinine should be monitored carefully. For its FDA approved indication (DVT prophylaxis during hip replacement surgery), its cost per day is approximately eight times more than LMWH. Even though monitoring is not routinely necessary according to the manufacturer for its approved indication, monitoring is frequently necessary when it is used in other clinical scenarios. Its higher cost than comparable therapies for DVT prophylaxis and the low availability of the FXa assay in most non-tertiary care hospitals has limited the widespread use of danaparoid. Danaparoid has been found to be effective in the treatment of HIT although this is an off label use, despite being the most frequent reason why danaparoid is used.
达那肝素钠(商品名:Orgaran,由欧加农公司生产)是一种类肝素糖胺聚糖抗血栓药物,已被批准用于预防择期髋关节置换手术患者术后深静脉血栓形成(DVT),后者可能导致肺栓塞(PE)。达那肝素是一种低分子量类肝素,由硫酸乙酰肝素(84%)、硫酸皮肤素(12%)和少量硫酸软骨素(4%)混合而成,其抗血栓活性已得到充分证实。其药理作用主要通过以高于肝素的比例抑制因子Xa(FXa)和IIa(FIIa)发挥,对血小板功能影响极小。与肝素或低分子量肝素(LMWH)相比,达那肝素与肝素诱导的抗体交叉反应性较低,因此是治疗肝素诱导的血小板减少症(HIT)的理想选择。皮下注射后,达那肝素具有良好的生物利用度。达那肝素对常规凝血试验(活化部分凝血活酶时间[aPTT]、凝血酶原时间[PT]和凝血酶时间[TT])影响很小。血清肌酐升高的患者应密切监测。就其FDA批准的适应证(髋关节置换手术期间预防DVT)而言,其每日费用约为LMWH的八倍。尽管根据制造商的说法,对于其批准的适应证通常无需监测,但在用于其他临床情况时,监测往往是必要的。与用于预防DVT的同类疗法相比,其成本较高,且大多数非三级医院缺乏FXa检测,限制了达那肝素的广泛应用。尽管这属于超适应证用药,但达那肝素已被发现可有效治疗HIT,这也是使用达那肝素最常见的原因。