dic彌散性血管內凝血診斷和治療進展

1、DIC的現狀CURRENT ASPECT OF DIC,,? DIC不是一種獨立的疾病而是一個由多種病因引起的出血性病理過程，其特征是微循環(huán)內發(fā)生廣泛的纖維蛋白沉積和血小板聚集，導致彌漫性微血栓形成，繼發(fā)性凝血因子和血小板大量消耗以及纖溶亢進，從而引起微循環(huán)障礙、出血與溶血等一系列嚴重的臨床癥狀。?國際血栓與止血學會的DIC定義：DIC是多種原因與成分引起的全身性血管內凝血過程。DIC的病理變化主要在微血管，并引起微血管病變，嚴重時

2、可導致臟器功能障礙。,Underlying Conditions Associated with DICBasic disease ratio of the disease to all (%)Infection diseases 36.94Obstetric complications 24.81Mal

3、ignancies 24.21Surgery and trauma 4.34Iatrogenic factor 1.45Other factors 8.25,,,,DIC

4、 is characterized by the increasing loss of localization or compensated control in coagulation activation.,,DIC pathogenesis is not just related to “coagulation gone haywire,” but fully involves all components of the inf

5、lammatory and innate immune response.,不同原因DIC的臨床特征,不同疾病引起的DIC的臨床表現不同。敗血癥DIC易發(fā)生腎臟損害；早期以組織缺血為特征，然后才有明顯的出血。創(chuàng)傷后DIC可能表現有成人呼吸窘迫綜合征。APL引起的DIC主要表現為出血。,彌?散?性?血?管?內?凝?血?診?斷?與?治?療?中?國?專?家?共?識（2012）,臨床表現：因原發(fā)病不同而差異較大1．出血：特點為自發(fā)性，嚴重者可發(fā)

6、生危及生命的出血。2．休克或微循環(huán)衰竭：早期即出現腎、肺、大腦等器官功能不全。3．微血管栓塞4．微血管病性溶血,彌?散?性?血?管?內?凝?血?診?斷?與?治?療?中?國?專?家?共?識（2012）,DIC的實驗室檢查包括兩方面，一是反映凝血因子消耗的證據，包括(PT、APTT、纖維蛋白原濃度及血小板計數；二是反映纖溶系統活化的證據，包括FDP、D一二聚體、3P試驗。,國際血栓與止血學會的分步驟分級診斷標準1 誘發(fā)因素

7、：患者是否有與DIC有關的基礎疾??？如果有，繼續(xù)以下步驟；如果沒有，不再繼續(xù)2 一般的凝血試驗（血小板計數，PT，纖維蛋白原，sFM或FDP）3  對一般的凝血試驗結果進行積分?血小板計數（>100 = 0；3sec但6sec = 2）?纖維蛋白原水平（>1.0g/l = 0；5：符合DIC；每日重復做檢測如<5：提示（但不肯定）為非顯性DIC；每1~2日重復檢測,麻省大學醫(yī)學中

8、心對DIC的常用指標的評價檢測指標 敏感性（%） 特異性（%） 診斷效率（%） 1． 單個試驗血小板計數 97 48 67PT 91 27 57APTT 91 42 57TT 83 60 70Fbg

9、 22 100 65AT 91 40 70 FDP 100 67 87D-D 91 68 80破碎紅細胞 23 73 512． 聯合試驗（幾個試驗均為陽性）PT+APTT+TT 83

10、 11 51 PT+APTT+Fbg 22 100 65PT+APTT+FDP 91 71 86FDP+D-D 91 94 95,,,,D-二聚體在DIC患者明顯增高,彌?散?性?血?管?內?凝?血?診?斷?與?治?療?中?國?專?家?共?識（2012）,1．治療基礎疾病及去除誘因：分別采取控制感染、治療腫瘤、

11、積極處理病理產科及外傷等措施，是終止DIC病理過程的最為關鍵和根本的治療措施。2．抗凝治療：阻止凝血過度活化、中斷DIC病理過程。應在處理基礎疾病的前提下，與凝血因子補充同步進行。臨床上常用普通肝素和低分子量肝素。,彌?散?性?血?管?內?凝?血?診?斷?與?治?療?中?國?專?家?共?識（2012）,3．替代治療：適用于有明顯血小板或凝血因子減少證據且DIC未能得到控制、有明顯出血表現者。(1)新鮮冷凍血漿等血液制品，也可使用冷沉

12、淀。纖維蛋白原水平較低時，可輸入纖維蛋白原。,彌?散?性?血?管?內?凝?血?診?斷?與?治?療?中?國?專?家?共?識（2012）,(2)血小板懸液：未出血的患者PLT<20×109/L，或者存在活動性出血且PLT<50×109/L的DIC患者。(3)FⅧ及凝血酶原復合物：偶在嚴重肝病合并DIC時考慮應用。4．其他治療：(1)支持對癥治療：抗休克治療，糾正缺氧、酸中毒及水電解質平衡紊亂。,,,彌?

13、散?性?血?管?內?凝?血?診?斷?與?治?療?中?國?專?家?共?識（2012）,(2)纖溶抑制藥物：臨床上一般不使用，僅適用于有明顯纖溶亢進的臨床及實驗證據，繼發(fā)性纖溶亢進已成為遲發(fā)性出血主要或唯一原因的患者。(3)激素治療：下列情況可予以考慮：①基礎疾病需糖皮質激素治療者。②感染中毒性休克合并DIC已經有效抗感染治療者。③并發(fā)腎上腺皮質功能不全者。,英國DIC治療指南（2009）,The cornerstone of the t

14、reatment is treatment of the underlying condition. Transfusion of platelets or plasma should be reserved for patients with bleeding. Severe hypofibrinogenaemia may be treated with fibrinogen or cryoprecipitate. In cases

15、of DIC where thrombosis predominates, heparin should be considered. Patients with DIC characterised by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues.,意大利DI

16、C治療指南（2012）,The treatment of the underlying disease. We do not suggest the use of AT or rFVIIa. Heparin or LMWH is not suggested except for thrombo-embombolic prophylaxis in patients without active bleeding. In patient

17、s with sepsis/DIC we suggest the use of hr APC. In patients with DIC and active bleeding we suggest transfusion therapy (platelets, plasma, cryoprecipitate). In patients with chronic DIC or without active bleeding we do

18、not suggest transfusion therapy based only on laboratory parameters.,Expert consensus for the treatment of DIC in Japan, 2010,In asymptomatic or bleeding DIC, LMWH, synthetic protease inhibitor (SPI), and AT are recommen

19、ded. In case of severe bleeding, SPI is recommended since it does not cause a worsening of bleeding. Blood transfusions are also required in cases of life threatening bleeding. In the organ failure type, including sepsis

20、, AT has been recommended. DIC with thrombosis and may thus require strong anticoagulant therapy, such as LMWH, UFH, and DS.,DIC and hyperfibrinolysis in acute promyelocytic leukemia,Zhaoyue WangJiangsu Institute of Hem

21、atologyThe Affiliated Hospital of Soochow UniversityChina,Alterations of SFC, FDP and D-dimer in APL patients n SFC(mg/L) FDP(pg/L) D-Dimer(pg/L)Control 40

22、 49.7±16.4 215.3±63.2 177.1±43.9DIC 15 958.6±202.3*** 764.4±97.8*** 15166±2788 *** Non-DIC 35 316.9±195.4*△ 322.8±175.2△

23、 2366±1135 △△△DIC corrected 6 376.7±123.6*△ 366.9±113.7△ 2579±1679 △△△ Compare with control，*P<005，**P<001， *** P <0001；Compare with DIC，△P<005，△△P<001，△△△P<

24、0001,,,,Sepsis-induced DIC with features of TTP: a fatal fulminant syndrome,DIC and TTP are different disease states，while ADAMTS13 deficiency could occur in sepsis-induced DIC. We report two patients who had septic DIC

25、with features of idiopathic TTP characterized by low ADAMTS13 activity and positive ADAMTS13 inhibitor. They had a specific fulminant course and fatal outcome, which might represent a new specific syndrome.,,女，43歲，因腹水住院檢

26、查。APTT 68.7s，PT 34.3s，TT 30.8s，Fg 1.2g/L，AT 41%，D二聚體7.1mg/L，血小板54×109/L。肝功能正常。B超發(fā)現膽管有一小包塊。手術與病理檢查證實為膽管癌廣泛轉移并發(fā)DIC。,男,64歲.皮膚瘀斑與血尿1月余,背部劇烈疼痛10天.有高血壓史.全身皮膚粘膜瘀點瘀斑,背部大片瘀斑與皮下血腫.Hb 58 g/L,血小板72 × 109/L.APTT 46.2s,PT 2

27、3.6s,TT 40.7s,纖維蛋白原1.30g/L,D-二聚體 31.5 mg/L.CT示主動脈夾層瘤.行主動脈支架與頸部動脈置管,手術部位出血不止.,男，12歲，出水痘后10天全身大面積瘀斑，消化道呼吸道與泌尿道出血，反復顱內大出血，濃度昏迷。血小板24×109/L，APTT、PT與TT明顯延長，纖維蛋白原0.21g/L，3P陽性，D-二聚體6.2mg/L。診斷DIC，大量輸注血液、血漿與纖維后無效。后加用大劑量止血芳酸與

28、抑肽酶后止血停止，很快蘇醒。,Case 3 was a 13 year-old female. Since the age of 6 months, a hemihypertrophy on the right side of her body became gradually apparent. In the age of 10 years, she had a problem of hip dislocation, and then

29、 was effectively treated by open reductiona. In the age of 12 years, she suffered from a severe hematochezia. Digital subtraction angiography revealed abnormality of vascular structure in her ascending colon. However, ab

30、dominal operation did not find any Meckel diverticulum or vascular tumour in her small intestine. In the age of 13 years, she was admitted to our hospital because of continuing gum bleeding.,,,,,,,Alterations of DIC mark

31、ers in two PS cases with giant hemangiomas  Platelets APTT PT TT Fibrinogen AT D-dimer (×109/L) (s) (s) (s) (g/

32、L) (%) (μg/L) Case 1Before splenectomy 71 61.7 20.1 22.8 0.6 50 19.1After splenectomy 110 37.2 14.4 18.2 2.91 83

33、 3.22Case 2Before splenectomy 81 44.9 14.7 24.0 0.34 70.4 18.0 After splenectomy 138 40.1 14.5 18.2 3.06 98.6 1.95

34、Normal control 100-300 28-40 10.8-13.5 14.0-21.0 2.00-4.00 70-125 0.01-0.50,,,,A scoring system for diagnozing Proteus syndromeMacrodactyly and/or hemihypertrophy 5 pointsPlantar or palmar cerebrifo

35、rm hyperplasia 4 pointsLipomas/subcutaneous tumours 4 pointsEpidermal naevus 3 pointsMacrocephaly and/or skull exostosis 2.5 pointsm

36、iscellaneous other minor abnormalities 1 pointA score of 13 or greater confirms its diagnosis. Our two patients scored 15.5 and 13 points, respectively, and met the criteria of Proteus syndrome diagnosis.,,,男，5歲

37、，皮下大片瘀斑。 WBC 8.7×109/L，RBC 3.67×1012/L，Hb 132 g/L，Plt 19×109/L。初診為ITP。,,女，43歲，因卵巢囊腫住院手術。術后3天每天均有大血腫。APTT 86.7s，PT> 120s，TT 15.8s，Fg 3.1g/L，血小板165×109/L。擬診為DIC。追問病史，因10年前瓣膜置換每日服用華法林（近半年為3mg/d），未作監(jiān)測。

38、,晚期肝硬化的凝血改變,男，52歲，晚期肝硬化肝功能衰竭，牙齦出血，皮膚少量瘀斑。APTT48.2s，PT31.4s，TT19.1s，纖維蛋白原0.87g/L，凝血酶原31%，因子Ⅴ42%，因子Ⅶ22.7%，因子Ⅷ104%，因子Ⅸ64%，因子Ⅹ37.8%，Ⅺ56.6%。,VOD,女，22歲。ALL化療后復發(fā)3次，接受來自母親的半相合骨髓移植。術后第5天出現腹痛、腹脹、黃疸與肝腫大；體重每日增加10斤。全身皮膚粘膜廣泛出血。T-BIL

39、 84.5μmol/L，ALT 1820 U/L， AST 2670U/L，LDH 2880 U/L。APTT 45.4s，PT 35.4s，TT 23.4s，Fg 1.03g/L，AT 38%，D二聚體3.18 mg/L，FⅤ:C 18%，FⅦ:C 4%，FⅧ:C 91%，FⅨ:C 23%，ADAMTS13 100%,Murine coagulation factor VIII is synthesized in endothelia

40、l cells,The primary cellular source of FVIII biosynthesis is controversial, with contradictory evidence supporting an endothelial or hepatocyte origin. Lman1 mutations result in combined deficiency of FV and FVIII, with

41、 levels of both factors reduced to ～10% to 15% of normal in human patients. Endothelial cells from multiple, but not all, tissues contribute to the plasma FVIII pool in the mouse. Blood. 2014;123(

42、24):3697-3705,女，2歲，外傷性肝破裂。入院后經大量輸血、纖維蛋白原并給予重組活化因子Ⅶ與血凝酶等止血藥物。經保守治療后出血停止，恢復進食，一般情況良好，但凝血檢查測不出，纖維蛋白原明顯降低，抗體凝血酶水平與血小板計數正常。擬診為DIC。,The diagnosis and treatment of DIC remain extremely controversial. Diagnosis and treatment DI