Department of Acute and Critical Care Medicine, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
J Thromb Haemost. 2019 Aug;17(8):1205-1216. doi: 10.1111/jth.14480. Epub 2019 Jun 5.
The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation (DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage-associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue-type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor-1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no-flow and low-flow times, patients without return of spontaneous circulation, and non-survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post-cardiac arrest syndrome.
本综述的目的在于证明心脏骤停和复苏中观察到的凝血和纤溶变化可被视为弥散性血管内凝血（DIC），并探讨 DIC 是否可作为治疗靶点的可能性。DIC 的触发因素（如损伤相关分子模式、炎症细胞因子和肾上腺素）的出现与血小板激活、明显的凝血酶生成和纤维蛋白形成、抗凝途径不足以及组织型纤溶酶原激活物增加纤溶有关，随后纤溶酶原激活物抑制剂-1 抑制纤溶，心脏骤停和复苏患者中会出现这种情况。同时观察到这些患者中存在中性粒细胞激活和内皮损伤，伴有糖萼扰动。在长时间心脏停搏前缺氧、无复流和低血流时间长、无自主循环恢复以及非幸存者的患者中，这些变化的程度更为严重。动物和临床研究证实，重要器官（包括大脑）的脑血流减少和微血管纤维蛋白血栓形成。心脏骤停和复苏患者的 DIC 临床诊断与多器官功能障碍有关，可通过序贯器官衰竭评估评分进行评估，并且死亡率增加。本综述证实，心脏骤停和复苏中的凝血-纤溶变化符合 ISTH 提出的 DIC 定义，且 DIC 与器官功能障碍和患者预后不良有关。这一证据表明，应考虑已确立的 DIC 作为心脏骤停后综合征的主要治疗靶点之一。
