Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA.
Ann Transl Med. 2015 May;3(Suppl 1):S11. doi: 10.3978/j.issn.2305-5839.2015.02.03.
Circulation and oxygenation of blood outside the body is commonly required during complex surgical interventions involving coronary pulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO). Both CPB and ECMO are life-supporting procedures utilizing a heart-lung machine, which subjects the blood to unphysiological conditions, potentially promoting undesirable blood coagulation. Traditionally, thrombotic complications from CPB and ECMO are resolved by heparin, an inexpensive broad spectrum anticoagulant that prevents blood clotting, but often results in bleeding. Despite hemostatic support therapy and constant monitoring, the lives of patients undergoing CPB and ECMO are often threatened by uncontrolled bleeding. There is an urgent need for novel strategies which provide safe anti-coagulation alternatives during CPB and ECMO procedures. Several non-traditional approaches, including nitric oxide donors as well as various protease and contact activation inhibitors, have been investigated and shown some success. More recently, Larsson et al. isolated a recombinant fully human (3F7) antibody inhibiting Factor XIIa. The antibody was shown to be both an efficacious and safe alternative to heparin. Below we will examine this study in more detail and offer considerations for translation of this novel concept to the clinic.
在涉及冠状动脉肺旁路 (CPB) 和体外膜氧合 (ECMO) 的复杂手术干预中,通常需要在体外循环和血液氧合。CPB 和 ECMO 都是使用心肺机进行生命支持的程序,使血液处于非生理状态,可能会促进不良的血液凝结。传统上,CPB 和 ECMO 的血栓并发症通过肝素解决,肝素是一种廉价的广谱抗凝剂,可防止血液凝结,但常导致出血。尽管进行了止血支持治疗和持续监测,但 CPB 和 ECMO 患者的生命仍经常受到不受控制的出血的威胁。迫切需要在 CPB 和 ECMO 手术期间提供安全抗凝替代方案的新策略。已经研究了几种非传统方法,包括一氧化氮供体以及各种蛋白酶和接触激活抑制剂,并取得了一些成功。最近,Larsson 等人分离出一种抑制因子 XIIa 的重组全人源 (3F7) 抗体。该抗体被证明是肝素的有效且安全的替代物。下面我们将更详细地研究这项研究,并考虑将这一新概念转化为临床应用。