如何处理大出血病人DIC

怎么处理大出血病人DIC,昆明医科大学第二附属医院麻醉科思永玉,CASE,多发性性创伤，术中4000ml血压几乎测不出，狂推肾上腺素。所有创面渗血，无法止血,CASE,APTT 120 s, PT 120s , Fib 0.6g/L问题：怎么了？A ： DICB： 凝血功能障碍,APTT（延长）：血浆加入接触因子+磷脂+Ca2+3243秒，延长10秒凝血因子Fib凝血酶原肝素或类肝素FDP抗凝活性,PT （延长）：血浆加入组织因子+Ca2+1113秒，超过对照值3秒以上为异常凝血因子Fib,TT（不变）：（凝血酶时间）标准化凝血酶+血浆16-18s，延长3s以上肝素或类肝素，FibFDP抗凝活性,Clot formation at injury site- A.,Bolliger et al. Anesthesiology 2010; 113:120519,Clot formation at injury site- B.,Bolliger et al. Anesthesiology 2010; 113:120519,Clot formation at injury site- C.,Bolliger et al. Anesthesiology 2010; 113:120519,Clot formation at injury site- D.,Bolliger et al. Anesthesiology 2010; 113:120519,为什么产生凝血功能障碍？,Effects of Hemodilution on Coagulation Factors,crystalloids, colloids, erythrocytes,Effects of Hemodilution on Coagulation Factors,FVIII and von Willebrand factor can be acutely increasedrelease from endothelium by stress hormones, including epinephrine and vasopressin,Effects of Hemodilution on Coagulation Factors and Blood Components,Fibrinogen = 1 g/L, loss of about 150% of circulating blood volumeTthe critical concentrations of enzymatic coagulation factors and platelet count are reached after a loss of 200% of blood volume,Effects of Hemodilution on anticoagulant factor,Antithrombin 抗凝血酶 (formerly antithrombin III) activity decreases to below 30% after 1:6 dilution with saline in vitro.Decreased antithrombin activity prolongs the half-lives of thrombin and activated FX,Bolliger D, et al. Br J Anaesth 2009; 102:7939.Jesty J, et al. Arterioscler Thromb Vasc Biol 2005; 25:24639,Effects of Hemodilution on Coagulation Factors,Bolliger D, I，et al. Br J Anaesth 2010; 104: 31825.,Effects of Hemodilution on Platelet,platelet count is often higher than predicted by the extent of dilutionrelease of platelets from the spleen and lungs and from the bone marrow in premature forms,Reed RL, 2nd, et al. Ann Surg 1986; 203:40 8,Role of the Activated Platelet,Systemic hypoperfusion drive acute coagulopathy - anticoagulation,Brohi et al. Current Opinion in Critical Care 2007, 13:680685,Systemic hypoperfusion drive acute coagulopathy - Hyperfibrinolysis,Brohi et al. Current Opinion in Critical Care 2007, 13:680685,Fibrinogen,Bolliger D, I，et al. Br J Anaesth 2010; 104: 31825.,Regulation of fibrin polymerization and fibrinolysis within the clot,Bolliger D, I，et al. Br J Anaesth 2010; 104: 31825.,Fibrin Polymerization and Fibrinolysis,Bolliger D, I，et al. Br J Anaesth 2010; 104: 31825.,Consumption of coagulation factors and platelets,moderate to severe lung contusionsConsumption be highly localized at the site of injury.手术创面大,John R. Hess. Blood and Coagulation Support in Trauma Care. Hematology Am Soc Hematol Educ Program. 2007:187-918.,Changes in thrombin-generation kinetics after hypothermia- and acidosis-induced in pigs,Martini WZ, et al. J Trauma. 2005;58:10021009; discussion 10091010.,Hypothermia and Acidosis: Thrombin Generation,Hypothermia primarily inhibits thrombin generation in the initiation phaseAcidosis severely impairs thrombin generation in the propagation phase,Wenjun Zhou Martini. J Trauma. 2009;67: 202209,Hypothermia and Acidosis: Fibrinogen Availability,Hypothermia inhibits fibrinogen synthesisAcidosis accelerates fibrinogen degradation, leading to a potential deficit in fibrinogen availability.,Wenjun Zhou Martini. J Trauma. 2009;67: 202209,Interventions for Coagulopathy,Initial Volume Resuscitationcrystalloids and colloids,Volume Resuscitation：crystalloids VS colloids,dilute the coagulation factorsstabilize systemic circulation,Volume Resuscitation：Transfusion of erythrocytes,improve oxygen carrying capacityfacilitate platelet aggregation by releasingadenosine diphosphate under shear flows,Joist JH, et al. Platelet adhesion and aggregation in pulsatile shear flow: Effects of red blood cells. Thromb Res 1998; 92:S4752,Fresh Frozen Plasma,FFP contains all the components in donor plasmaProcoagulant anticoagulantantifibrinolytic factors albumin immunoglobulins.,Thawed FFP,Downes KA, et al. Transfusion 2001; 41:570,FFP: RBC,Massive Transfusion Protocols， MTPsRBC：FFP：Plt = 1:1:1,Brian P. McGlinch. Anesthesia for Trauma & Emergency Surgery. In: John F. Butterworth IV, David C. Mackey, John D. Wasnick. Morgan & Mikhails Clinical Anesthesiology. 5th ed. New York: McGraw-Hill Education, 2013:87-122.,The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital,Borgman MA et al . J Trauma. 2007 Oct;63(4):805-13.,massive transfusion protocols should utilize a 1:1 ratio of plasma to RBCs,coagulation products,plasma, PLT, and cryoprecipitate products significantly increased 30-day survival in trauma patients,Shaz BH, et al. Transfusion 2010; 50:493500,Evidence-based practice guidelines for plasma transfusion,Should plasma transfusion (vs. no plasma) be used in trauma patients requiring massive transfusion?Recommendation: We suggest that plasma be transfused to trauma patients requiring massive transfusion (quality of evidence = moderate).,John D. Roback et al. TRANSFUSION 2010;50:1227-1239.,Evidence-based practice guidelines for plasma transfusion,Should a plasma : red blood cell (RBC) transfusion ratio of 1:3 or more (vs. 1:3) be used in trauma patients requiring massive transfusion?Recommendation: We cannot recommend for or against transfusion of plasma at a plasma : RBC ratio of 1:3 or more in trauma patients during massive transfusion (quality of evidence = low).,John D. Roback et al. TRANSFUSION 2010;50:1227-1239.,Cryoprecipitate,cryoprecipitate is rich in fibrinogen, FXIII, von Willebrand factor, and FVIII,什么时候输注冷沉淀,欧洲麻醉学会的指南推荐Fib1.52g/L就输注冷沉淀欧洲的创伤出血管理指南：Fib1g/L，输注冷沉淀,Rolf Rossaint, et al. Management of bleeding following major trauma: an updated European guideline. Critical Care 2010, 14:R52.,Sibylle A, et al. Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30:270382.,输注的量,One unit (15 ml) of cryoprecipitate per 10 kg of body weight is estimated to increase plasma fibrinogen by 0.5 g/l in the absence of continuing bleeding.30 ml/kg FFP is required to raise the plasma fibrinogen level by 1 g/l,Solomon C， et al. Br J Anaesth 2010; 104:555 62,Chowdhury P, et al. Br J Haematol 2004; 125: 69 73,Platelet Concentrates,the administration of platelet concentrates has to be considered if platelet count falls below 50 109/L,抗血小板药物,阿司匹林,氯吡格雷（波立维）,输注FFP的指征,PT、APTT大于正常对照 1.5倍，创面弥漫性渗血大量库血输入引起的稀释性凝血功能障碍紧急对抗华法林的抗凝作用,ASA：FFP指征,Correction of excessive microvascular bleeding (i.e., coagulopathy) in the presence of a PT greater than 1.5 times normal or INR greater than 2.0, or an aPTT greater than 2 times normal correction of excessive microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume (approximately 70 ml/kg) and when PT or INR and aPTT can not be obtained in a timely fashion,Anesthesiology, V 105, No 1, Jul 2006,ASA：FFP指征,urgent reversal of warfarin therapycorrection of known coagulation factor deficiencies for which specific concentrates are unavailableheparin resistance (antithrombin III deficiency) in a patient requiring heparin.,Anesthesiology, V 105, No 1, Jul 2006,FFP 或冷沉淀,RBC,冷沉淀 RBC:FFP 【 1:1 】【 2:1 】【3:1】,血小板,目标：Hb 7g/dL,tranexamic acid 氨甲环酸,负荷量 1 g 10 min持续输注1 g over 8 h,CRASH-2 trial collaborators. Lancet 2010; 376:2332,CRASH-2. Lancet,Shakur H, et al. Lancet 2010; 376:2332,without increasing vascular occlusive events,氨甲环酸抑制纤溶的机制,Pier mannuccio mannucci . hemostatic drugs. N Engl J Med. 1998. 339(4): 245-253,European guideline: Management of bleeding following major traum