Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Programa de Glicobiologia, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro, RJ, 21941-590, Brazil.
Thromb Haemost. 2010 May;103(5):1005-15. doi: 10.1160/TH09-11-0761. Epub 2010 Mar 9.
Increasing reports of bleeding and peri- or post-operative blood dyscrasias in Brazil were possibly associated with the use of heparin from bovine instead of porcine intestine. These two pharmaceutical grade heparins were analysed for potential differences. NMR analyses confirmed that porcine heparin is composed of mainly trisulfated disaccharides -->4-alpha-IdoA2S-1-->4-alpha-GlcNS6S-1-->. Heparin from bovine intestine is also composed of highly 2-sulfated alpha-iduronic acid residues, but the sulfation of the alpha-glucosamine units vary significantly: approximately 50% are 6- and N -disulfated, as in porcine heparin, while approximately 36% are 6-desulfated and approximately 14% N -acetylated. These heparins differ significantly in their effects on coagulation, thrombosis and bleeding. Bovine heparin acts mostly through factor Xa. Compared to porcine heparin on a weight basis, bovine heparin exhibited approximately half of the anticoagulant and antithrombotic effects, but similar effect on bleeding. These two heparins also differ in their protamine neutralisation curves. The doses of heparin from bovine intestine required for effective antithrombotic protection and the production of adverse bleeding effects are closer than those for porcine heparin. This observation may explain the increasing bleeding observed among Brazilian patients. Our results suggest that these two types of heparin are not equivalent drugs.
越来越多的出血和围手术期血液学异常的报告可能与使用牛来源而非猪来源的肝素有关。对这两种药用级肝素进行了潜在差异分析。NMR 分析证实，猪肝素主要由三硫酸化二糖组成-->4-α-IdoA2S-1-->4-α-GlcNS6S-1-->。牛肠来源的肝素也由高度硫酸化的 α-艾杜糖醛酸残基组成，但 α-葡萄糖胺单元的硫酸化程度差异很大：约 50%为 6-和 N-二硫酸化，如猪肝素，而约 36%为 6-脱硫酸化，约 14%为 N-乙酰化。这些肝素在对凝血、血栓形成和出血的影响上有显著差异。牛肝素主要通过 Xa 因子起作用。与基于体重的猪肝素相比，牛肝素的抗凝和抗血栓作用约为其一半，但对出血的影响相似。这两种肝素在鱼精蛋白中和曲线方面也存在差异。用于有效抗血栓保护和产生不良出血作用的牛肠来源肝素剂量与猪肝素更接近。这一观察结果可能解释了巴西患者出血增加的现象。我们的结果表明，这两种类型的肝素不是等效药物。
