1. Coagulopathy in Trauma Seunghwan Kim, M.D. Dept. of Emergency Medicine College of Medicine, Yonsei University

3. Objective Normal hemostasis Pathogenesis of coagulopathy in trauma patients Evaluation of coagulopathy Treatment

4. Coagulopathy Definition Failure of the blood to clot normally in response to tissue injury from trauma, surgery, or routine invasive procedures.

5. Normal Hemostasis

17. Coagulopathy

18. Risk factors for coagulopathy Acidosis (pH < 7.1) Hypothermia (core temp. < 34 ℃ ) Severe injury (ISS > 25) Shock (SBP < 70 mmHg) Cosgriff et al, J Trauma. 1997;42:857-861

19. Pathogenesis of coagulopathy Hemodilution Hypothermia Consumption of clotting factors Metabolic derangments

20. The “Bloody Vicious Cycle” Vigorous fluid resuscitation Hemodilution Increased bleeding Recurrent Hypotension

21. Hemodilution Dilutional thrombocytopenia  m/c of the coagulation abnormalities  35-40% of platelets remain in circulation after replacement of one blood volume Dilution of procoagulant factors  Fibrinogen : most sensitive  Massive transfusion

22. Hypothermia Bleeding : risk factor of hypothermia Quantitative and qualitative platelet dysfunction Alteration of coagulation enzyme kinetics Disruption of fibrinolytic equilibrium

23. Platelets Thrombocytopenia  Platelet sequestration in the liver and spleen Reduction of thromboxane B2 Inhibition of platelet aggregation Reversible on rewarming

24. Coagulation factors Clotting studies  Temperature is an important role  PT is most sensitive Altered enzyme kinetics in the coagulation cascades Increased fibrinolysis

25. Clotting factor depletion Multiple injury Massive clotting factor activation Uncontrolled activation of the fibrinolytic system

28. Lung and brain injury Severe pulmonary contusion BBB breakdown after brain injury Release of tissue thromboplastin Intravascular activation of coagulation Vigorous fibrinolysis Profile of DIC develops

29. Liver injury Site of synthesis for all coagulation factors except factor VIII Severe liver injury  Production of coagulation factors decreased  Massive transfusion, hypothermia…

30. Metabolic derangements Acidosis d/t hemorrhage shock Decrease coagulation enzyme activity Correlation between coagulation abnormalities and the hypotension duration Hypoperfusion is associated consumptive coagulopathy

33. Massive Transfusion Replacement of the patient’s entire blood volume within a 24-h period Replacement of 50% of the total blood volume within 3h Transfusion of more than 20 RBC units Need for at least 4 RBC units within 4h with continued major bleeding Blood loss exceeding 150ml/min Need for platelet and plasma replacement

34. Massive Transfusion Hypothermia  Transfusion of large volumes of cold blood product  Impairs the function of platelets  Potential for hypocalcemia Dilutional thrombocytopenia

35. Massive Transfusion Acid-Base change  Stored RBCs and whole blood; acidic pH  Sodium citrate Converted to sodium bicarbonate  Net effect : alkalosis  Routine administration of bicarbonate with large transfusion; undesirable

36. Massive Transfusion Citrate  Decreased levels of ionized calcium  Hypocalcemia Hypotension, narrowed pulse pressure, elevated LVEDP, PAP and CVP, ECG abnormality Factor IV

37. Evaluation

38. History Medication  Warfarin, asprin, NSAIDs Known bleeding disorder Bleeding tendency  Bruising tendency  Excessive bleeding during medical procedure  Prolonged menorrhea  Repeated or severe epistaxis

39. Physical Exam Bruising Joint abnormalities Petechiae, purpura Ecchymosis, Telangiectasia Hepatosplenomegaly Malnutrition

40. Prothrombin time (PT) Adding thromboplastin, containig TF, phospholipid and calcium to citrate plasma Extrinsic pathway and common pathway Affected by vitamin K-dependent factors INR = log patient PT / log control PT

41. Partial Thromboplastin Time Adding partial thromboplastin, activating substance and calcium to citrate plasma Intrinsic pathway and common pathway Factor VII is not measured

42. Platelet Count Quantitative measure of circulating platelets Counts < 50,000/mm 3  Increase bleeding from cut surfaces Counts < 20,000/mm 3  spontaneous bleeding

43. Bleeding Time Only test that measures platelet function and primary hemostasis Relatively insensitive and nonspecific May not predict surgical bleeding

44. Thrombin Time Adding thrombin to citrate plasma Time for conversion of fibrinogen to fibrin TT Prolonged  Fibrinogen is deficient or abnormal  Presence of circulating anticoagulant  Excessive fibrinolysis

45. Fibrinogen As clotting increases the fibrinogen level decreases Low level; consumptive condition  DIC, sepsis, severe traumatic brain injury Acute phase reactant

46. Thrombelastography (TEG) Analyze various characteristics of clot formation; computer analysis and graphic form data Platelet function Coagulation enzyme activity Fibrinolysis Overall degree of coagulability

48. Fibrin Split Products (FSPs) Not diagnositic Evidence of a consumptive process such as DIC D-dimer; most closely associated with DIC

49. Treatment

50. Prevention Easier than treating it once it develops Keep the patient warm and perfused Transfusion therapy; pay close attention to blood composition  Minimize use of non-blood fluids  RBC, plasma, platelet

52. Packed RBC Packed RBC 1p  RBCs; 195mL  Suspendig fluid; 155mL (Plasma 35mL) Acidic Citrate Low temperature

53. Platelet 1U ; increase 10,000/uL 50mL anticoagulated plasma 20 to 24 ℃ storage Low acid and thermal burden

54. Fresh Frozen Plasma (FFP) 250mL, Plasma 80% 500mg fibrinogen 200U of all of the other coagulation factors

55. Cryoprecipitate Freezing and thawing FFP Concentrates fibrinogen, vWF, Factor VIII, XIII FFP is the better product

57. Plasma transfusion Low level of evidence Closed laboratory monitoring of hemostasis Rapid blood loss Single plasma doses; 10-15 ml/kg Cryoprecipitate; 1-1.5packs/10 kg Consider time to thaw and transfer plasma

58. Clotting Factor Concentrate Factor VIII  Hemophilia A  Greenmono ® Factor IX  Hemophilia B  Facnyne ®

60. Recombinant Factor VIIa For hemophilia with inhibitor or factor VII deficiency In large doses requires only fibrinogen, thrombin and platelets to produce clotting “Off label” use in trauma  Reduction in bleeding in several studies NovoSeven ®  Very expensive

61. Rule of thumb in coagulopathy Prevention Recognize the major mechanism and treat it Recognize the general pace of normal patients Establish treatment goals Steady hand on the blood product spigot

62. References

63. Mauricio Lynn et al., Updates in the management of severe coagulopathy in trauma patients, Intensive Care Med, 2002 28:S241-S247 Ray Armand et al., Treating coagulopathy in trauma patients, Transfusion Medicine Reviews, Vol 17, No3, 2003: pp223-231 Paul J. Wojciechowski et al., Coagulopathy in massive transfusion, Int Anesthesiol Clin. 2005 Fall;43(4):1-20 Deborah M. Stein, Richard P. Dutton, Uses of recombinant factor VIIa in trauma, Curr Opin Cirt Care 2004 10:520-528 Peter Hellstern, Hannelore Haubelt, Indication for plasma in massive transfusion, Thrombosis Research 107 (2002) S19-22 D. Stainsby et al., Management of massive blood loss: a template guideline, Br J Anaesth 2000; 85:487-91