Suryanarayan Deepa, Schulman Sam
Department of Medicine and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada; Department of Medicine, University of Calgary, AB, Canada.
Department of Medicine and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Thromb Res. 2014 May;133 Suppl 2:S158-66. doi: 10.1016/S0049-3848(14)50026-6.
The prescription of new oral anticoagulants is on the rise. As opposed to vitamin K antagonists and heparins the new agents have single targets in the coagulation cascade, more predictable pharmacokinetics and they lack validated and available antidotes. In general, the new agents have similar or lower bleeding risk than vitamin K antagonists, especially risk of intracranial bleeding. Risk factors for bleeding are typically the same for old and new anticoagulants. Old age, renal dysfunction and concomitant antiplatelet agents seem to be recurring risk factors. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. With the exception of vitamin K (for vitamin K antagonists) and protamine (for heparin) the same array of prohemostatic agents--unactivated or activated prothrombin complex concentrate, and activated factor VIIa--have been tried for almost all anticocoagulants in different models, and for some agents also in patients, with varying success. Hemodialysis can reduce the level of dabigatran efficiently and activated charcoal may be used for very recent oral ingestion of lipophilic agents. In view of the shorter half life of the new agents compared to warfarin the need for reversal agents may be less critical. Nevertheless, highly specific reversal agents for the thrombin- and factor Xa-inhibitors are under development and might be available within two years.
新型口服抗凝药的处方量正在上升。与维生素K拮抗剂和肝素不同，新型药物在凝血级联反应中有单一靶点，药代动力学更可预测，且缺乏经过验证且可用的解毒剂。总体而言，新型药物的出血风险与维生素K拮抗剂相似或更低，尤其是颅内出血风险。新旧抗凝药的出血危险因素通常相同。老年、肾功能不全和同时使用抗血小板药物似乎是反复出现的危险因素。充分的支持治疗和暂时停用所有抗血栓药物是严重出血并发症管理的基础。除了维生素K（用于维生素K拮抗剂）和鱼精蛋白（用于肝素）外，相同系列的促止血药物——未活化或活化的凝血酶原复合物浓缩物以及活化的凝血因子VIIa——已在不同模型中针对几乎所有抗凝药进行了试验，对一些药物也在患者中进行了试验，效果各异。血液透析可有效降低达比加群的水平，活性炭可用于近期口服的亲脂性药物。鉴于新型药物的半衰期比华法林短，对抗凝逆转剂的需求可能不那么迫切。尽管如此，针对凝血酶和因子Xa抑制剂的高度特异性逆转剂正在研发中，可能在两年内问世。
