de Jonge E, Levi M, Stoutenbeek C P, van Deventer S J
Department of Intensive Care, Academic Medical Center, University of Amsterdam, The Netherlands.
Drugs. 1998 Jun;55(6):767-77. doi: 10.2165/00003495-199855060-00004.
Disseminated intravascular coagulation (DIC) can be caused by a variety of diseases. Experimental models of DIC have provided substantial insight into the pathogenesis of this disorder, which may ultimately result in improved treatment. Disseminated coagulation is the result of a complex imbalance of coagulation and fibrinolysis. Simultaneously occurring tissue factor-dependent activation of coagulation, depression of natural anticoagulant pathways and shutdown of endogenous fibrinolysis all contribute to the clinical picture of widespread thrombotic deposition in the microvasculature and subsequent multiple organ failure. Cornerstone for the treatment of DIC is the optimal management of the underlying disorder. At present, specific treatment of the coagulation disorders themselves is not based on firm evidence from controlled clinical trials. Plasma and platelet transfusion are used in patients with bleeding or at risk for bleeding and low levels of coagulation factors or thrombocytopenia. The role of heparin and low molecular weight heparin is controversial, but their use may be justified in patients with active DIC and clinical signs of extensive fibrin deposition such as those with meningococcal sepsis. There is some evidence to indicate that low molecular weight heparin is as effective as unfractionated heparin but may be associated with a decreased bleeding risk. Antithrombin III (AT III) replacement appears to be effective in decreasing the signs of DIC if high doses are administered, but effects on survival or other clinically significant parameters are at best uncertain. If AT III supplementation is used, the dosage should be selected to achieve normal or supranormal plasma levels of 100% or higher. Results of studies on protein C concentrate, thrombomodulin or inhibitors of tissue factor are promising, but the efficacy and safety of these novel strategies remains to be established in appropriate clinical trials.
弥散性血管内凝血（DIC）可由多种疾病引起。DIC的实验模型为深入了解这种疾病的发病机制提供了大量信息，这最终可能会改善治疗效果。弥散性凝血是凝血和纤溶复杂失衡的结果。同时发生的组织因子依赖性凝血激活、天然抗凝途径的抑制以及内源性纤溶的停止，都导致了微血管广泛血栓形成以及随后多器官功能衰竭的临床表现。治疗DIC的基石是对潜在疾病的最佳管理。目前，针对凝血障碍本身的特异性治疗并非基于对照临床试验的确凿证据。对于有出血或有出血风险且凝血因子水平低或血小板减少的患者，可使用血浆和血小板输注。肝素和低分子肝素的作用存在争议，但对于有活动性DIC且有广泛纤维蛋白沉积临床体征的患者（如脑膜炎球菌败血症患者），使用它们可能是合理的。有证据表明，低分子肝素与普通肝素效果相当，但出血风险可能更低。如果给予高剂量抗凝血酶III（AT III）替代治疗，似乎能有效减轻DIC的体征，但对生存率或其他临床重要参数的影响充其量尚不确定。如果使用AT III补充治疗，应选择合适剂量以达到血浆水平正常或超正常，即100%或更高。关于蛋白C浓缩物、血栓调节蛋白或组织因子抑制剂的研究结果很有前景，但这些新策略的疗效和安全性仍有待在适当的临床试验中确定。
