D isseminated I ntravascular C oagulation

1. Disseminated Intravascular Coagulation Huang Honghui Dept. of Hematology, Renji Hospital

2. Definition • DIC: clinicopathologic syndrome • widespread intravascular coagulation is induced by procoagulants that are introduced into or produced in the blood circulation and overcome the natural anticoagulant mechanisms.

3. Etiology

5. Stage of hypocoagulability Stage of hypercoagulability Stage of secondary fibrinolysis

6. Pathophysiology • Stage of hypercoagulability • Stage of hypocoagulability due to excess of consumption of blood coagulation factors • Stage of secondary fibrinolysis

7. Typing of DIC

8. Clinical features • Bleeding • Thromboembolism • Circulatory disturbance, shock • Microangiopathic hemolytic anemia

9. Clinical features • Bleeding • Mechanism • consumption of hemostatic components including platelets, fibrinogen, and other coagulation factors; • secondary fibrinolysis; • anticoagulant effects of fibrinogen/fibrin degradation products; • manifestations • Skin and mucosa:petechiae, ecchymosis, oozing from veni-punctures, arterial lines, catheters, and injured tissues; • internal organ:massive bleeding into the gastrointestinal, lungs, central nervous system, or orbit.

12. Clinical features • Thromboembolism

14. Clinical features • Circulatory disturbance, shock Ⅻ Ⅻa kininogen kallidini formation of Fibrinopeptide A microvascular thrombi Fibrinopeptide B thrombin dilatation of the blood vessles returned blood volume↓ vasospasm hemorrhage SHOCK circulating blood volume ↓ diseases underlying DIC

15. Clinical features • Microangiopathic hemolytic anemia • Mechanism • Erythrocytes are injured mechanically during passage through fibrin networks in the microcirculation. • Manifestation • production of schistocytes and microspherocytes; • jaundice, hemoglobinuria, anemia.

16. Direction of blood flow Fibrin

18. Laboratory features • Basic blood examinations • Platelet count: BPC ↓ • Peripheral blood smear: schistocytes (in approximately 50% of cases)

20. Laboratory features • The coagulation defect • Partial thromboplastin time (PTT) • Prothrombin time • Thrombin time • Fibrinogen concentration

21. Laboratory features • Tests for fibrinolysis • Fibrinogen degradation products (FDP) • D-dimer • Plasma protamine paracoagulation test (3P) • Euglobulin lysis time

22. Laboratory features • Other laboratory findings(molecular markers) • F1+2 • Thrombin-AT Ⅲ complex (TAT) • Fibrinopeptide A (FPA) • SFMC (soluble fibrin monomer complex) • Antithrombin Ⅲ • Products of platelet activation:β-TG,PF-4,TXB2,GMP-140 • PIC (plasmin-α2 plasmin inhibitor complex)

23. Ⅹa prothrombin thrombin +ATⅢ TAT F1+2 fibrinogen fibrin monomer FPA,FPB Polymerization soluble fibrin plasmin ⅩⅢa FDP cross-linked fibrin SFMC: FDP(X)+FM+Fg

24. Laboratory features • Laboratory data change with remarkable rapidity in DIC, and in doubtful cases, it is often important to repeat the tests at frequent intervals, even every 8 to 12 hours and observing the dynamics of the process.

25. Diagnostic criteria ------ ISTH DIC score

26. 1.Risk assessment: does the patient have an underlying disorder known to be associated with overt DIC? If yes: Proceed. If no: Do not use this algorithm.

27. 2. Order global coagulation tests platelet count, prothrombin time, fibrinogen, fibrin-related marker

28. 3. Score global coagulation test results. • Platelet count (>100 = 0; <100 = 1; < 50 = 2) • Elevated fibrin related marker (e.g. D-dimers; fibrin degradation products) (no increase = 0; moderate increase = 2; strong increase = 3) • Prolonged prothrombin time (< 3 s = 0; > 3 but < 6 s = 1; > 6 s = 2) • Fibrinogen level (>1.0g/L = 0; < 1.0g/L = 1)

29. 4. Calculate score If ≥ 5: compatible with overt DIC: repeat score daily If < 5: suggestive (not affirmative) for non-overt DIC: repeat next 1–2 days.

30. Differential diagnosis • DIC and severe liver disease • DIC and TTP

31. The distinction between DIC and severe liver disease

32. The distinction between DIC and TTP

33. Treatment • Management of underlying disorders • intensive antibiotic treatment in patients with gram-negative bacteremia; • hysterectomy in patients with abruptio placenta; • resection of an aortic aneurysm; • debridement of crushed tissues; • chemotherapy of acute leukemia; • supportive care: fluids, pressors, dialysis, and respiratory and ventilator management.

34. Heparin

35. mechanism lysine sites active arginine serine reactive center center Thrombin antithrombin heparin

36. Treatment: anticoagulation1.heparin • Indications • forms manifested by thrombosis or acrocyanosis • forms that accompany • cancer, • vascular malformations, • retained dead fetus, • acute promyelocytic leukemia.

37. Treatment: anticoagulation1.heparin • Dosage • The optimal dosage of heparin is the source of some disagreement; • 50u/kg, intravenous infusion, Q6h • 5000-10000u, subcutaneously,Q12-24h

38. Treatment: anticoagulation1.heparin • Laboratory monitoring • aPTT: a prolongation of between 1.5 and 2 times normal; • CT; • Reversal of heparin effect • 1mg protamine sulfate : 100u heparin • infused intravenously • rate of infusion < 5mg/min

39. Treatment: anticoagulation1.heparin low-molecular- weight heparin (LMWH)

40. Treatment: anticoagulation1.heparin • LMWH • Characteristics • Posses higher anti-Ⅹa activity than anti-thrombin activity; • Longer half-time and a higher, more reliable bioavailability • A lower incidence of bleeding complications. • Usage • 75-150IUA Ⅹa/Kg.d, subcutaneously, ×3-5days.

41. Treatment: anticoagulation2. others • AT-Ⅲ • Decrease the dose of heparin; • Improve the response. • Dose: 1500-3000u Bid-Tid, intravenous infusion×5-7days;

42. Treatment: Antiplatelet drugs • Indications • in hypercoagulability state; • the diagnosis of DIC is still not certain; • in mild cases. • Usage • compound danshen infusion 20-40ml Bid-Tid×3-5days • Low molecular weight dextran 500-1000ml/d ×3-5days • Ticlopidine 250mg Bid p.o. ×5-7days • Dipyridamole 500mg/d ×3-5days;

43. Treatment: Haemostatic support • platelet concentrates • platelet count <20×109/L or have severe life-threatening bleeding; • fresh frozen plasma (FFP) • 10-15ml/kg body weight when the INR of PT is greater than 1.5; • cryoprecipitate • 1-4 unit/10kg body weight when the fibrinogen concentration is 0.8g/l or less. • Fibrinogen • 1st dose: 2-4g (1-1.5g→↑50mg/L) • PPSB • 200u=200ml FFP

44. Treatment: Fibrinolytic inhibitors • Indications • the underlying disorders have already controlled or cured; • excessive fibrinolysis is observed; • Late stage of DIC; • Contraindications • patients with early stage of DIC.

45. Treatment: Fibrinolytic inhibitors • Usage • PAMBA(氨甲苯酸) 600-800mg/d • tranexamic acid(氨甲环酸) 500-700mg/d • ε-aminocaproic acid(氨基已酸) 4-10g/d • Attention • These agents should be preceded by replacement of depleted blood components and continuous heparin infusion.

46. Summary

47. 治疗：总结 • DIC各期治疗原则 • 早期 • 首选肝素加血小板聚集抑制药； • 禁用纤溶抑制药； • 不需输血及补充凝血因子；

48. 治疗：总结 • DIC各期治疗原则 • 中期 • 肝素治疗为主； • 适当输血及补充凝血因子； • 在应用肝素基础上慎重使用小剂量抗纤溶药；

49. 治疗：总结 • DIC各期治疗原则 • 晚期 • 抗纤溶药以及输血补充凝血因子为主； • 如不能确定血管内凝血是否终止可同时使用小剂量肝素；