Greinacher Andreas
Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität, Diagnostikzentrum, Greifswald, Germany.
Semin Thromb Hemost. 2004 Jun;30(3):315-27. doi: 10.1055/s-2004-831044.
One of the most important adverse drug reactions that physicians encounter is the life- and limb-threatening prothrombotic syndrome known as heparin-induced thrombocytopenia (HIT). Unfractionated heparin (UFH), administered during cardiopulmonary bypass (CPB), is highly immunogenic. Heparin-dependent antibodies can develop in 25 to 50% of UFH-treated cardiac surgery patients within 5 to 10 days. These antibodies can activate platelets and are considered the causative agents of HIT. HIT is a relatively common complication, occurring in 1 to 3% of cardiovascular surgery patients when UFH administration is continued postoperatively. It is strongly associated with new thromboembolic events leading to limb amputation and death. In acute or recent (< 100 days) HIT, alternative anticoagulatory regimens are needed during CPB surgery for prevention of HIT-related thrombosis. Treatment options for such patients now generally include the use of alternative anticoagulants such as lepirudin, bivalirudin, or danaparoid, as well as a combined treatment with platelet-function inhibitors and heparin. In patients with a history of HIT and no detectable antibodies, heparin is currently the safest approach for high-dose anticoagulation during CPB. Before and after surgery, however, alternative anticoagulants should be used. The risk of clinical HIT after heart surgery could potentially be reduced by using low-molecular-weight heparins for postsurgery anticoagulation.
医生遇到的最重要的药物不良反应之一是称为肝素诱导的血小板减少症(HIT)的危及生命和肢体的血栓前综合征。在体外循环(CPB)期间给予的普通肝素(UFH)具有高度免疫原性。在接受UFH治疗的心脏手术患者中,25%至50%会在5至10天内产生肝素依赖性抗体。这些抗体可激活血小板,被认为是HIT的致病因素。HIT是一种相对常见的并发症,当术后继续使用UFH时,在1%至3%的心血管手术患者中发生。它与导致肢体截肢和死亡的新的血栓栓塞事件密切相关。在急性或近期(<100天)HIT中,CPB手术期间需要替代抗凝方案以预防HIT相关血栓形成。此类患者的治疗选择现在通常包括使用替代抗凝剂,如比伐芦定、阿加曲班或达那肝素,以及与血小板功能抑制剂和肝素联合治疗。在有HIT病史且未检测到抗体的患者中,肝素目前是CPB期间高剂量抗凝最安全的方法。然而,在手术前后,应使用替代抗凝剂。通过使用低分子量肝素进行术后抗凝,可能会降低心脏手术后临床HIT的风险。