2. Zhao Mingyao BMC.ZZU Coagulation-anticoagulation balance & imbalance of haemostatic system Chapter 9

4. Section 1 Overview of haemostatic system Thrombin Fibrin Plasmin FDP ?..... Coagulation and blood flowing

5. Clot formation (electron microscope)

6. TF liver endothelium TM

7. Ⅷ、Ⅸ、 Ca 2+ + plt Ⅹ、Ⅴ、 Ca 2+ + plt Complex formation of clotting factors Plt

8. 1.Prothrombin activator formation 2. Thrombin formation 3.Fibrin formation 3 steps of coagulation

9. Section 2 Imbalance in haemostatic system

10. Coagulation system Extrinsic system Intrinsic system Anticoagulation system VEC Microcirculation TFPI, PC, PS, AT-III, Heparin Coagulation status Change TF XIIa other factor fibrinolysis balance & imbalance of Coagulation-anticoagulation

11. Major types 1.Bleeding disorder: inherited ~ & acquired ~ 2.Thrombogenesis and thrombotic disorders 3.Blood vessel abnormity: VEC, Factors activation 4.Fibrinolytic factors abnormity

12. Twinkle Dwivedi‘s body ooze blood through her eyes, feet and even her head everyday von Willebrand factor

13. Section 3 Disseminated Intravascular Coagulation (DIC)

14. Concept of DIC Acquired blood coagulation disorder = thrombosis + / or bleeding Coagulation is always the initial event

15. Part 1 Etiology of ~ Acute ~ : infection ( G- & G+ ) 30% obstetric accident 18% serious trauma 10% malignant tumor 9% Amniotic fluid embolism; abruptio placentae Retained dead fetus Rheumatologic illness

16. Part 2 Pathology of DIC Fibrin deposition, thrombosis Bleeding Edema Organ failure

17. Part 3 Pathogenesis of DIC 1. Hypercoagulation ? 2. Consumptive hypocoagulayion ? 3. Secondary fibrinolysis ?

18. 1.TF release into blood and hyperexpression Septicemia Injury Obstetric accident Tumor TF - VIIa Ca 2+ ? ? ? ?

19. 2. VEC lesion (1) TF (1) TF expression: (2) TFPI↓: Degradation of TM/PC and HS/AT-III system (3) Fibrinolysis inhibited: t-PA ↓, PAI-1↑ (4) Plt adherence and aggregation: Collagen exposure, though NO, PGI 2 and ADP enzyme ↑ (5) XII activation: XII+HMWK+PK(prekallirein) +XI

20. I mpaired VEC + Plt Normal VEC

21. 3.Entrance of procoagulant to blood ① Snake venom ② Metastatic tumor ③ Pathogenic microorganism ④ Foreign particles: amniotic fluid ⑤ Trypsin (proteolytic enzyme)

23. 4.blood cell damage (1) RBC: TF, ADP (2) WBC: leukemia, endotoxin,, IL-1, TNFa (3) Plt:

25. Part 4 Predisposing factors for DIC

26. (1)Mononuclear phagocyte system dysfunction GC and particles closing MPS

27. 巨噬细胞吞噬 Macrophage colibacillus coccus

28. iv ET 18 ~ 24 Hr Iv thorium dioxide iv ET General Shwartzman Reaction GSR

29. (2) Liver dysfunction Deactivation: IX, X, XI, Replenishing: plasminogen, α 2 -antiplasmin, AT-III, PC Release TF

30. (3)Hypercoagulable state Pregnancy : clotting factors ↑, plt ↑, but t-PA, u-PA, AT-III, PC ↓; TF rich in placenta Acidosis: heparin activity↓ CF activity ↑ Plt aggregation ↑

31. Activity of TF tissue activity of TF （ u/mg ） Liver 10 muscle 20 Brain 50 lung 50 Placenta 2000

32. (4) Microcirculation dysfunction *Blood stagnation *Plt aggregation *Acidosis: VEC damage

33. Part 5 Clinical classification of ~ 1.Acute ~ : several hrs ~ 1 or 2 d 2.Subacute ~: some days, malignancies, retained dead fetus 3.Chronic ~ : over months, connective tissue disorder SLE

34. Part 6 Typical clinical manifestation of ~ Bleeding Shock MOF(MODS) MHA

35. 1. Bleeding (1)Consumption of coagulant and plt (2)activation of fibrinolytic system (3) formation of FDP fibrin monomer to polymerize(Im) thrombin (IIa) plts inhibit

36. Patient with DIC bleed DIC 出 血（腹 主动脉 瘤术后）

37. 2.Organ dysfunction Thromboembolism ischemia Ischemia-reperfusion injury Inflammatory reaction out of control in body

38. 3.Shock Bleeding Coronary thrombosis Vascular dilation Microcirculatory thrombosis

39. 4. 4. Microangiopathic Hemolytic Anemia Schistocyte > 2% RBC: * mechanic damaged * fragile [' ʃ istəsait

40. RBC hang on fibrin rope net （ screen electroscope L  2000 ， R  5200 ）

41. Part 7 P Part 7 Principles of prevention and treatment for DIC 1.Management of the underlying disorder 2.Improving the microcirculation 3.Reconstructing the balance of coagulation and fibrinolysis heparin/AT-III/PC+low mol dextran +dipyridamole+ PC +EACA /or streptokinase, urokinase Epsilon-Aminocaproic Acid (EACA)

42. Pathophysiological Basis of DIC diagnosis & Treatment Diagnosis 1.Disease history 2.Clinic manifestation 3.Lab test 3+1

43. Lab test 3+1 Screen test (3 items) 1.Plt: <100 000/mm 3 ( 100 000 ~ 300 000) 2.Plasma fibrinogen count: <150 mg% (200~400) 3.PT: prolonged 3 sec (13~15 sec ) Confirm test 3P test 1.D-dimer or “3P ” positive The plasma-protamine-paracoagulation-(3-P-) test

44. Coagulation test Ⅻ Ⅺ plt Ⅴ Ca 2+ Ⅹ TF( Ⅲ ) Ⅶ Ca 2+ plt Ⅷ Ⅸ Ⅱ Ⅰ ⅠmⅠm Ca 2+ ⅠmⅠm ⅠmⅠm ⅠmⅠm Ⅹ III I net fibrin plasmin FDP ACT APTT PT

45. DIC Score Relates to Mortality Rate in Adults with Severe Sepsis Overt DIC No Overt DIC

46. Fbg IIa D-dimer Test XⅢaXⅢa PLn FDP ( D monomer ) A,B,C,X,Y,D,E FDP ( D dimer ) Second fibronolysis A,B,C,X,Y,D,E Fbn FM Primary fibronolysis PLn

47. Keep equilibrium anywhere and anytime Zhao Mingyao