抗凝血酶 III
这一药物是一种主要的凝血级联抑制剂;在患DIC 时其水平降低。其同时具有抗凝血和抗炎特性。治疗目标为 AT III 达到正常水平的 125% 至 150%。这一药物可能有助于减轻感染性休克患者的 DIC。[5]Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001;286:1869-1878.http://www.ncbi.nlm.nih.gov/pubmed/11597289?tool=bestpractice.com抗凝血酶 III 替代疗法取决于多种因子的测定水平。同时使用不同因子将很可能增强疗效。然而这一药物的效力尚未得到证实,目前尚不能推荐使用。
组织因子途径抑制物 (TFPI)
TFPI 与组织因子以及因子 VIIa 和因子 Xa 结合,从而抑制凝血酶原生成凝血酶。早期临床研究表明,TFPI 可能是一种具有前景的 DIC 治疗选择,尽管之后进行的一项 3 期研究并未发现总生存期获益。[6]Abraham E, Reinhart K, Demeyer I, et al. Efficacy and safety of Tifacogin (recombinant tissue pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003;290:238-247.http://www.ncbi.nlm.nih.gov/pubmed/12851279?tool=bestpractice.com
活化的重组因子 VII (rFVIIa)
对于存在与 DIC 相关的难治性重度出血发作的患者,可考虑使用这种新药物。[7]Franchini M, Manzato F, Salvagno GL, et al. Potential role of recombinant activated factor VII for the treatment of severe bleeding associated with disseminated intravascular coagulation: a systematic review. Blood Coagul Fibrinolysis. 2007;18:589-593.http://www.ncbi.nlm.nih.gov/pubmed/17890943?tool=bestpractice.com[8]Moscardo F, Perez F, de la Rubia J, et al. Successful treatment of severe intra-abdominal bleeding associated with disseminated intravascular coagulation using recombinant activated factor VII. Br J Haematol. 2001;114:174-176.http://www.ncbi.nlm.nih.gov/pubmed/11472364?tool=bestpractice.com
重组水蛭素(r-水蛭素)
直接抑制凝血酶。使用 r-水蛭素的动物研究已证明其对治疗 DIC 有效。[9]Munoz MC, Montes R, Hermida J, et al. Effect of the administration of recombinant hirudin and or tissue-plasminogen activator (T-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. Br J Haematol. 1999;105:117-121.http://www.ncbi.nlm.nih.gov/pubmed/10233373?tool=bestpractice.com
重组组织因子途径抑制物 (TFPI)
抑制外源性途径并阻滞内毒素相关凝血酶生成,目前正处于一项 3 期大型临床试验。[6]Abraham E, Reinhart K, Demeyer I, et al. Efficacy and safety of Tifacogin (recombinant tissue pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003;290:238-247.http://www.ncbi.nlm.nih.gov/pubmed/12851279?tool=bestpractice.com[10]Bajaj MS, Bajaj SP. Tissue pathway inhibitor: potential therapeutic applications. Thromb Haemost. 1997;78:471-477.http://www.ncbi.nlm.nih.gov/pubmed/9198199?tool=bestpractice.com[11]Abraham E. Tissue factor inhibition and clinical trials results of tissue pathway inhibitor in sepsis. Crit Care Med. 2000;28:S31-S33.http://www.ncbi.nlm.nih.gov/pubmed/11007194?tool=bestpractice.com
重组线虫抗凝剂 c2 (NaPc2)
组织因子/因子 VIIa 和因子 Xa 之间三元复合体的一种强效、特异性抑制剂。在动物模型中能够抑制凝血活化。[12]Moons AH, Peters RJ, Cate H, et al. Recombinant nematode anticoagulant protein c2, a noval inhibitor of tissue factor-factor VIIa activity, abrogates endotoxin-induced coagulation in chimpanzees. Thromb Haemost. 2002;88:627-631.http://www.ncbi.nlm.nih.gov/pubmed/12362234?tool=bestpractice.com
重组白介素 (IL)-10
一种抗炎细胞因子。调节凝血并消除内毒素对凝血的作用。[13]Pajkrt D, van der Poll T, Levi M, et al. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood. 1997;89:2701-2705.http://www.ncbi.nlm.nih.gov/pubmed/9108387?tool=bestpractice.com
重组人可溶性血栓调节蛋白 (ART-123)
血栓调节蛋白是内皮细胞表面上的一种凝血酶受体。重组人可溶性血栓调节蛋白 (ART-123) 血栓调节蛋白的活化的细胞外结构域。其通过减少凝血酶介导的凝血以及凝血部位的蛋白 C 激活发挥作用。这一制剂同时具有抗炎特性。一项评价该药物安全性和有效性的全球随机、双盲、安慰剂对照、2b 期研究结果表明患有脓毒症和疑似 DIC 的患者死亡率获益的临床证据。[14]Vincent JL, Ramesh MK, Ernest D, et al. A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation. Crit Care Med. 2013;41:2069-2079.http://www.ncbi.nlm.nih.gov/pubmed/23979365?tool=bestpractice.com