Comprehensive Stroke Center, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 170 Villarroel, 08036, Barcelona, Spain.
J Neurol. 2012 Feb;259(2):212-24. doi: 10.1007/s00415-011-6153-3. Epub 2011 Jul 5.
The incidence of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) is growing due to the increasing use of warfarin and the older age of treated patients. Recent population studies reveal that OAC-ICH currently occurs at a frequency comparable to that of subarachnoid hemorrhage. Most frequently, OAC-ICH are located in deep or lobar regions of the brain, although it may also occur in the brainstem. These hemorrhages are larger than spontaneous hematomas and may be fatal in at least 50% of cases. The primary cause of brain injury in patients with OAC-ICH is the direct mechanical disruption of the brain tissue but secondary damage may occur through the intervention of matrix metalloproteinases, glutamate, cytokines, heme, iron, and the chemical toxicity of products such as thrombin, which are released from the clot. The pathogenesis of OAC-ICH also includes the effects of aging, the level of anticoagulation, genetic factors, and a high prevalence of concurrent cerebrovascular conditions, such as cerebral amyloid angiopathy, leukoaraiosis or previous strokes. The treatment of OAC-ICH is challenging and involves rapid reversal of anticoagulation with hemostatic drug therapies such as vitamin K, fresh frozen plasma, prothrombin complex concentrates or recombinant factor VIIa. These therapies may not always be sufficient to stabilize the patient's clinical condition and lacking randomized controlled trials, the best hematological approach to reverse oral anticoagulation is debated. Other difficult decisions reviewed in this article are whether anticoagulation should be restarted after OAC-ICH, and when anticoagulant treatment should be resumed. The newer oral anticoagulants, which are increasingly being introduced for thromboembolism prevention, may confer a lower risk of intracranial bleeding than warfarin, although they do not have an antidote and their anticoagulant effect is difficult to monitor.
口服抗凝药物相关脑出血(OAC-ICH)的发病率由于华法林的广泛应用以及治疗患者年龄的增长而不断增加。最近的人群研究表明,OAC-ICH 的发生率与蛛网膜下腔出血相当。OAC-ICH 最常发生于脑深部或脑叶,尽管也可能发生于脑干。这些出血比自发性血肿更大,至少有 50%的病例可能致命。OAC-ICH 患者脑损伤的主要原因是脑组织的直接机械破坏,但通过基质金属蛋白酶、谷氨酸、细胞因子、血红素、铁以及凝血酶等从血栓中释放的产物的化学毒性等的干预,可能会发生继发性损伤。OAC-ICH 的发病机制还包括衰老、抗凝水平、遗传因素以及脑淀粉样血管病、脑白质病变或既往中风等并存脑血管病的高发等因素的影响。OAC-ICH 的治疗具有挑战性,涉及通过止血药物治疗(如维生素 K、新鲜冷冻血浆、凝血酶原复合物浓缩物或重组 VIIa 因子)快速逆转抗凝。这些治疗方法并不总是足以稳定患者的临床状况,并且由于缺乏随机对照试验,关于逆转口服抗凝的最佳血液学方法仍存在争议。本文还回顾了其他困难的决策,即 OAC-ICH 后是否应重新开始抗凝,以及何时应恢复抗凝治疗。新型口服抗凝药物越来越多地用于预防血栓栓塞,其颅内出血风险可能低于华法林,尽管它们没有解毒剂,且其抗凝作用难以监测。