Service Anesthésie, Réanimation Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France.
INSERM UMRS1140, Université Paris Descartes, Paris, France.
Clin Appl Thromb Hemost. 2018 Dec;24(9_suppl):8S-28S. doi: 10.1177/1076029618806424. Epub 2018 Oct 8.
Disseminated intravascular coagulation (DIC) is an acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition in the vasculature, organ dysfunction, consumption of clotting factors and platelets, and life-threatening hemorrhage. Disseminated intravascular coagulation is provoked by several underlying disorders (sepsis, cancer, trauma, and pregnancy complicated with eclampsia or other calamities). Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches. Therapeutic strategies specific for DIC aim to control activation of blood coagulation and bleeding risk. The clinical trials using DIC as entry criterion are limited. Large randomized, phase III clinical trials have investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis, but the diagnosis of DIC was not part of the inclusion criteria. Treatment with APC reduced 28-day mortality of patients with severe sepsis, including patients retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with APC did not have any positive effects in other patient groups. The APC treatment increased the bleeding risk in patients with sepsis, which led to the withdrawal of this drug from the market. Treatment with AT failed to reduce 28-day mortality in patients with severe sepsis, but a retrospective subgroup analysis suggested possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or TM have been carried out showing promising results. The efficacy and safety of other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin) or transfusion of platelet concentrates or clotting factor concentrates have not been objectively assessed.
弥散性血管内凝血(DIC)是一种获得性临床生物综合征,其特征为广泛的凝血激活导致纤维蛋白在血管内沉积、器官功能障碍、凝血因子和血小板消耗以及危及生命的出血。弥散性血管内凝血由多种潜在疾病(感染、癌症、创伤和妊娠并发子痫或其他灾难)引起。治疗潜在疾病和消除触发机制是关键的治疗方法。针对 DIC 的治疗策略旨在控制血液凝固的激活和出血风险。以 DIC 为入选标准的临床试验有限。大型随机、III 期临床试验已经研究了抗凝血酶 (AT)、活化蛋白 C (APC)、组织因子途径抑制剂 (TFPI) 和血栓调节蛋白 (TM) 在脓毒症患者中的疗效,但 DIC 的诊断不是纳入标准的一部分。APC 治疗降低了严重脓毒症患者 28 天死亡率,包括回顾性归入脓毒症相关 DIC 亚组的患者。APC 治疗对其他患者群体没有任何积极影响。APC 治疗增加了脓毒症患者的出血风险,导致该药物从市场撤出。AT 治疗未能降低严重脓毒症患者 28 天死亡率,但回顾性亚组分析表明 DIC 患者可能有效。已经进行了使用重组 TFPI 或 TM 的临床研究,结果有希望。其他抗凝剂(即未分级肝素、低分子量肝素)或血小板浓缩物或凝血因子浓缩物的输血的疗效和安全性尚未得到客观评估。