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低分子量肝素和类肝素概述:基础与临床方面

Overview of low molecular weight heparins and heparinoids: basic and clinical aspects.

作者信息

Hirsh J

机构信息

Hamilton Civic Hospitals Research Centre, Ontario, Canada.

出版信息

Aust N Z J Med. 1992 Oct;22(5):487-95.

PMID:1280097
Abstract

Low molecular weight heparins (LMWHs) are fragments derived by enzymatic or chemical depolymerization of standard heparin (SH). They are approximately one-third the size of SH, with a mean molecular weight of 4,000 to 6,000. LMWHs produce less bleeding for equivalent antithrombotic effects than SH in experimental animals. Clinically LMWHs exhibit different pharmacokinetics than SH; they have much better bioavailability at low doses, a longer half life than SH and clearance pattern which is dose independent. In addition, LMWHs have a more predictable dose response than SH. These differences in pharmacokinetic properties occur because in contrast to SH, LMWHs show minimal binding to endothelium and plasma proteins. Clinical trials have demonstrated that LMWHs are effective and safe for the prevention and treatment of venous thromboembolism. In patients having orthopaedic surgery, LMWHs are more effective than low dose SH, more effective than dextran or warfarin. They are also more effective than SH in preventing venous thrombosis in stroke patients and those suffering spinal injury. In addition, recent studies suggest that LMWHs administered by subcutaneous injection in fixed weight-adjusted doses are at least as effective and safe as adjusted dose SH given by continuous intravenous infusion for the treatment of venous thrombosis.

摘要

低分子量肝素(LMWHs)是通过对标准肝素(SH)进行酶解或化学解聚而得到的片段。它们的大小约为SH的三分之一,平均分子量为4000至6000。在实验动物中,对于同等的抗血栓形成作用,LMWHs引起的出血比SH少。在临床上,LMWHs表现出与SH不同的药代动力学;它们在低剂量时具有更好的生物利用度,半衰期比SH长,且清除模式与剂量无关。此外,LMWHs的剂量反应比SH更可预测。这些药代动力学特性的差异之所以出现,是因为与SH不同,LMWHs与内皮细胞和血浆蛋白的结合极少。临床试验表明,LMWHs在预防和治疗静脉血栓栓塞方面是有效且安全的。在接受骨科手术的患者中,LMWHs比低剂量SH更有效,比右旋糖酐或华法林更有效。在预防中风患者和脊髓损伤患者的静脉血栓形成方面,它们也比SH更有效。此外,最近的研究表明,以固定体重调整剂量皮下注射LMWHs,在治疗静脉血栓形成方面至少与连续静脉输注调整剂量的SH一样有效和安全。

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