Hanslik Thomas, Prinseau Jacques
Department of Internal Medicine, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Am J Cardiovasc Drugs. 2004;4(1):43-55. doi: 10.2165/00129784-200404010-00005.
Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.
使用抗维生素K(AVK)进行抗凝对于血栓栓塞事件的一级和二级预防非常有效。然而,关于过度抗凝的风险及管理仍存在问题。对于华法林所致的过度抗凝的逆转,可根据抗凝过度的程度、活动性出血的存在及部位、患者特征以及使用AVK的指征,采用停用AVK、口服或胃肠外给予维生素K、凝血酶原复合物或新鲜冰冻血浆等方法。在抗凝过度的患者中,维生素K旨在迅速将国际标准化比值(INR)降至安全范围,以降低大出血风险,从而改善患者预后,同时避免因过度纠正、对AVK耐药或对药物过敏反应而使患者面临血栓栓塞风险。当INR超过4.0 - 6.0时,出血风险会急剧增加,尽管绝对出血风险仍然相当低,每天每1000人中<5.5例。患者特征,包括高龄、接受治疗的高血压、中风病史以及同时使用多种药物等,都会影响出血风险。与过度纠正相关的血栓栓塞绝对风险似乎与过度抗凝所致的出血风险处于同一范围。在华法林抗凝过度的患者中,使用维生素K比单纯停用华法林能更快降低过高的INR;然而,尚未明确证明维生素K治疗实际上能降低大出血风险。由于静脉途径给予维生素K可能会出现类过敏反应,皮下途径给予会出现皮肤反应,因此首选口服给药。口服1 - 2.5mg植物甲萘醌(维生素K₁),可在24 - 48小时内将INR范围从5.0 - 9.0降至2.0 - 5.0,对于INR>10.0的情况,5mg剂量可能更合适。如果使用上述剂量的维生素K,不太可能出现INR过度纠正或对华法林耐药的情况。与华法林治疗后相比,醋硝香豆素或苯丙香豆素治疗后出现过度抗凝时,维生素K的效果较差。