Mechanism of low-molecular-weight heparin reversal by platelet factor 4
Mechanism of low-molecular-weight heparin reversal by platelet factor 4
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DOI：
10.1016/j.thromres.2008.12.047
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发表时间：
2009-05-01
影响因子：
7.5
通讯作者：
Mackie, Ian M.
中科院分区：
文献类型：
--
作者：
Fiore, Martine M.;Mackie, Ian M.
低分子量肝素（LMWH）通过加速Xa因子（fXa）和凝血酶的抗凝血酶（AT）失活而发挥其抗凝作用。为了解决LMWH活性中钙依赖性模板机制的假设，我们在动力学测定中比较了肝素中和剂血小板因子4（PF 4）抑制各种治疗性LMWH的能力。PF 4的中和系数和PF 4对各种LMWH的表观亲和力以分子量依赖的方式增加。硫酸鱼精蛋白通过非特异性机制中和肝素。EDTA消除了fXa-AT反应的钙依赖性加速，表明桥接机制对LMWH活性有显著贡献。在低分子量肝素浓度范围内（
Low-molecular-weight heparins (LMWH) exert their anticoagulant effect by accelerating anti-thrombin (AT) inactivation of factor Xa (fXa) and thrombin. To address the hypothesis of a calcium-dependent template mechanism in LMWH activity, we compared the ability of the heparin neutralising agent Platelet Factor 4 (PF4) to inhibit various therapeutic LMWH in a kinetic assay. Neutralization coefficients by PF4 and apparent affinities of PF4 for various LMWH increased in a molecular weight-dependent manner. Protamine sulphate neutralized heparin via a non-specific mechanism. EDTA abolished the calcium-dependent acceleration of the fXa-AT reaction, indicating that the bridging mechanism contributed significantly to LMWH activity. Within a low range of LMWH concentration (