Department of Anesthesiology and Critical Care Medicine, Division of Acute and Critical Care Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Department of Acute and Critical Care Medicine, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
Thromb Haemost. 2024 Mar;124(3):181-191. doi: 10.1055/a-2165-1142. Epub 2023 Sep 1.
Two phenotypes of disseminated intravascular coagulation (DIC) are systematically reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic phenotype is the activation of coagulation, insufficient anticoagulation with endothelial injury, and plasminogen activator inhibitor-1-mediated inhibition of fibrinolysis, leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic phenotype is defined as massive thrombin generation commonly observed in any type of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying disorder that results in severe bleeding due to excessive plasmin formation. Three major pathomechanisms of systemic hyperfibrinogenolysis have been considered: (1) acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial cells and t-PA-rich storage pools, (2) enhancement of the conversion of plasminogen to plasmin due to specific proteins and receptors that are expressed on cancer cells and endothelial cells, and (3) alternative pathways of fibrinolysis. DIC with fibrinolytic phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin degradation products (FDPs), and the FDP/D-dimer ratio are important for the diagnosis of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears to be one of the few methods to be effective in the treatment of systemic pathologic hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms, establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic phenotype are urgent issues in the field of thrombosis and hemostasis.
系统回顾了两种弥散性血管内凝血（DIC）表型。DIC 分为血栓形成和纤维蛋白溶解表型，分别以血栓形成和出血为特征。血栓形成表型 DIC 的主要病理是凝血激活、内皮损伤导致抗凝不足以及纤溶抑制物-1 介导的纤溶抑制，导致微血管纤维蛋白血栓形成和器官功能障碍。纤维蛋白溶解表型 DIC 定义为任何类型 DIC 中常见的大量凝血酶生成，伴有潜在疾病引起的全身病理性过度纤维蛋白原降解，导致由于过多纤溶酶形成而严重出血。系统性过度纤维蛋白原降解的三个主要发病机制已被考虑：（1）缺氧内皮细胞和富含组织型纤溶酶原激活物（t-PA）的储存池释放 t-PA 的加速；（2）由于癌细胞和内皮细胞上表达的特定蛋白和受体，纤溶酶原向纤溶酶的转化增强；（3）纤溶的替代途径。通过 DIC 诊断后识别全身性病理性纤维蛋白（原）降解，即可诊断纤维蛋白溶解表型 DIC。低纤维蛋白原水平、高纤维蛋白原和纤维蛋白降解产物（FDP）以及 FDP/D-二聚体比值对诊断全身性病理性纤维蛋白（原）降解很重要。目前，缺乏针对纤维蛋白溶解表型 DIC 的循证治疗策略。氨甲环酸似乎是治疗全身性病理性纤维蛋白（原）降解有效的少数方法之一。阐明纤维蛋白溶解表型 DIC 的发病机制、建立诊断标准和治疗策略的国际合作是血栓形成和止血领域的紧迫问题。
