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Coagulopathy

Coagulopathy. Bundarika Suwanawiboon M.D. Yingyong Chinthammitr M.D. Theera Ruchutrakool M.D. Division of Hematology Department of Medicine Faculty of medicine Siriraj Hospital Bangkok Thailand 10700. Coagulopathy. Bundarika Suwanawiboon M.D. Yingyong Chinthammitr M.D.

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Coagulopathy

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  1. Coagulopathy Bundarika Suwanawiboon M.D. Yingyong Chinthammitr M.D. Theera Ruchutrakool M.D. Division of Hematology Department of Medicine Faculty of medicine Siriraj Hospital Bangkok Thailand 10700

  2. Coagulopathy Bundarika Suwanawiboon M.D. Yingyong Chinthammitr M.D. Theera Ruchutrakool M.D.

  3. Coagulopathy

  4. Normal Hemostasis Normal hemostasis • Blood vessel • Platelet • Coagulation factors • Fibrinolytic system • Natural anticoagulants

  5. Red blood cell Platelet

  6. Red blood cell Platelet

  7. Red blood cell Platelet Von Willebrand factor

  8. Red blood cell Platelet Von Willebrand factor

  9. Red blood cell Platelet Von Willebrand factor

  10. Red blood cell Platelet Von Willebrand factor

  11. Red blood cell Platelet Von Willebrand factor

  12. Red blood cell Platelet Von Willebrand factor

  13. Red blood cell Platelet Von Willebrand factor

  14. Red blood cell Platelet Von Willebrand factor

  15. Red blood cell Platelet Von Willebrand factor

  16. Red blood cell Platelet Von Willebrand factor Fibrin polymer

  17. Red blood cell Platelet Von Willebrand factor Fibrin polymer

  18. Red blood cell Platelet Von Willebrand factor Fibrin polymer

  19. Normal Hemostasis Normal hemostasis • Blood vessel • Platelet • Coagulation factors • Fibrinolytic system • Natural anticoagulants

  20. Normal Hemostasis Blood vessel • Endothelium • Connective tissue or collagen

  21. Normal Hemostasis Blood vessel • Endothelium Thrombogenesis • von Willebrand factor • Tissue thromboplastin • Endothelin Antithrombotic Effect • Thrombomodulin • Platelet derived relaxing factor (PDRF) • Prostacyclin (PGI2) • Tissue plasminogen activator

  22. Normal Hemostasis Blood vessel • Endothelium • Connective tissue or collagen

  23. Normal Hemostasis Blood vessel • Endothelium • Connective tissue or collagen • Collagen direct bind and activate platelet • Release von Willebrand factor to bind platelet

  24. Normal Hemostasis Platelet • Adhesion • via glycoprotein (GP) • Shape change • from disc to ameboid form • Release • ADP, thromboxane A2, vWF • Aggregation • via glycoprotein (GP)

  25. Normal Hemostasis Platelet

  26. Normal Hemostasis Platelet • Platelet plug formation and vasoconstriction • Primary hemostatic plug formation which is enough to stop bleeding from small and shallow wound

  27. Normal Hemostasis Coagulation pathway Factor XII HMWK/PK Factor XI Factor XIa Factor IX Factor IXa Factor VIIa Factor VIIIa Tissue factor Factor X Factor Xa Factor X Factor Va Prothrombin Thrombin Fibrinogen Fibrin

  28. Normal Hemostasis Extrinsic pathway Factor XII HMWK/PK Factor XI Factor XIa Factor IX Factor IXa Factor VIIa Factor VIIIa Tissue factor Factor X Factor Xa Factor X Factor Va Prothrombin Thrombin Fibrinogen Fibrin Intrinsic pathway Common pathway

  29. Normal Hemostasis Coagulation pathway Factor XII HMWK/PK Factor XI Factor XIa Factor IX Factor IXa Factor VIIa Factor VIIIa Tissue factor Factor X Factor Xa Factor X Factor Va Prothrombin Thrombin Fibrinogen Fibrin

  30. Normal Hemostasis Natural anticoagulant Factor XII HMWK/PK Factor XI Factor XIa Factor IX Factor IXa Factor VIIa Factor VIIIa Tissue factor Factor X Factor Xa Factor X Factor Va Prothrombin Thrombin Fibrinogen Fibrin heparin antithrombin Activated proteinC Protein S ProteinC

  31. Normal Hemostasis Fibrinolytic system • High Molecular Weight Kininogen (HMWK) • Prekallekrein (PK) • F.XII • Tissue plasminogen activator (t-PA) • Urokinase Fibrin polymer Plasminogen Plasmin Fibrin degradation products (FDP) Streptokinase

  32. Normal Hemostasis “New concept !” Cell-based model of coagulation

  33. Normal Hemostasis 1. Initiation TF-Cell Hemostasis occurs on two surfaces:TF- bearing cells and platelet IIa 3. Propagation 2. Amplification Activated Platelet IIa Platelet

  34. X prothrombin VIII/vWF VIIIa TF VIIa Xa Va TF-expressing cell thrombin V Va VIIa TF IX XI XIa thrombin prothrombin IXa platelet X IX Xa Va IXa VIIIa XIa Activated platelet Hoffman M et al. Blood Coagul Fibrinolysis. 1998; 9(suppl 1): S61-S65.

  35. X prothrombin VIII/vWF VIIIa TF VIIa Xa Va TF-expressing cell thrombin V Va VIIa TF IX XI XIa prothrombin thrombin IXa platelet X IX Xa Va IXa VIIIa XIa Activated platelet Hoffman M et al. Blood Coagul Fibrinolysis. 1998;9(suppl 1):S61-S65.

  36. Cell-based model “Three overlapping phases” • Initiation phase “TF-bearing cell to generate F.Xa, F.IXa and (little amount of) thrombin” • Amplification phase “Gererate cofactor F.V and F.VIII by little amount of thrombin from initiation phase” • Propagation phase “Large amount of thrombin production (burst of thrombin) on activated platelet”

  37. Approach to Hemostatic Disorders: Clinical and Laboratory Approach Bundarika Suwanawiboon, M.D. Division of Hematology Department of Medicine

  38. What is the diagnosis?

  39. Clinical Evaluation of Bleeding Patients • “80% of correct diagnosis can be made by history taking and physical examination.”

  40. History Taking • Identify if the bleeding problem is due to • Local vs. systemic defect • Location: single vs. multiple sites • Severity: Spontaneous? Appropriate to trauma? • Hereditary vs. acquired disorder • Onset • Family history • Underlying disease • Medication • Primary vs. secondary hemostatic disoder

  41. Primary Hemostasis Secondary Hemostasis Onset Immediate Delayed Sites • Skin • Mucosal • Others Superficial • Petechiae, superficial ecchymosis • Common • Rare Deep • Deep ecchymosis, hematoma • Rare • Retroperitoneal hematoma, hemarthrosis

  42. Primary Hemostatic defect Secondary Hemostatic defect

  43. Laboratory Investigation of Hemostatic Disorders

  44. Assessment of Primary Hemostasis • Platelet • Complete blood count (CBC) • Bleeding time/ PFA-100 • Platelet aggregation study • Blood vessel • Bleeding time • von Willebrand factor (vWF) • Bleeding time • vWF Antigen, vWF: RCO, vWF multimer, FVIII

  45. Complete Blood Count (CBC) • Platelet number • Normal platelet count: 150,000 –400,000/uL • > 100,000/uLBleeding unlikely • < 20,000/uL↑ risk for spontaneous bleeding • Must exclude pseudothrombocytopenia • Assess for platelet morphology

  46. Thrombocytopenia Giant platelet Pseudothrombocytopenia Bernard-Soulier Syndrome

  47. Etiology of Thrombocytopenia • Decreased Production • Hypoproliferation • Ineffective Thrombopoiesis • Aplastic Anemia, Amegakaryocytic • thrombocytopenia, infection, toxins, drugs • Infiltrative marrow disease, TAR • Megaloblastic anemia • Alloimmune, Autoimmune: ITP, SLE • DIC, TTP, HUS • Increased Destruction • Immune • Non-immune • Others • Splenic sequestration • Dilutional • Hypersplenism • Massive blood transfusion

  48. Bleeding Time

  49. Bleeding Time: Interpretation • Normal value* : 1-9 min • Prolonged bleeding time: • Thrombocytopenia/ anemia (Hct < 20%) • Hereditary platelet dysfunction • von Willebrand disease • Severe hypofibrinogenemia • Blood vessels disorders • Uremia • Myeloproliferative disorders • Medication: Aspirin, NSAIDs,other antiplatelet drugs

  50. Platelet Aggregation Study

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