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Hemostasis Balancing Act: Role of Pro-Clotting and Anti-Clotting Mechanisms

Explore the delicate balance in hemostasis with pro-clotting and anti-clotting factors, plug formation, fibrin cascade, and laboratory tests like platelet count, bleeding time, PT, and PTT. Understand the Intrinsic and Extrinsic pathways, where tissue factor comes from, and the importance of maintaining clotting under control.

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Hemostasis Balancing Act: Role of Pro-Clotting and Anti-Clotting Mechanisms

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  1. General Principles of Hemostasis Kristine Krafts, M.D.

  2. Hemostasis is a balancing act! pro-clotting anti-clotting plugs up holes in blood vessels keeps clotting under control

  3. Pro-Clotting clot

  4. Pro-Clotting vessels platelets cascade

  5. Pro-Clotting Blood vessel constricts. • Blood loss decreases • Platelets and factors meet

  6. Pro-Clotting Platelets form a plug. • Proteins are exposed • Platelets adhese • Granules release contents • Platelets aggregate • Phospholipids are exposed

  7. Pro-Clotting Fibrin seals up plug. • Tissue factor is exposed • Cascade begins • Cascade makes fibrin • Fibrin solidifies plug

  8. Intrinsic Extrinsic Coagulation Cascade thrombin exposed TF XII XIIa XI XIa TF VIIa IX IXa VII VIIIa VIII Final common pathway X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  9. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  10. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  11. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  12. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  13. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  14. Where does tissue factor come from? • “Hidden” cells exposed during injury • Microparticles floating in blood • Endothelial cells and monocytes (during inflammation)

  15. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  16. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  17. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  18. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  19. Extrinsic Intrinsic TF VII IX VIII X V thrombin fibrin clot

  20. tissue factor fibrin clot

  21. busy simple distracting riveting sinful sexy

  22. Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  23. SINtrinsic Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin busy clot fibrinogen fibrin distracting sinful

  24. SEXtrinsic Intrinsic Extrinsic thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin simple fibrinogen fibrin riveting sexy clot

  25. SINtrinsic SEXtrinsic TF VII IX VIII X V thrombin fibrin clot

  26. Anti-Clotting clot 1 cascade inhibition

  27. Intrinsic Extrinsic TFPI ATIII protein C thrombin exposed TF XI XIa TF VIIa IX IXa VII VIIIa VIII X Xa Va V prothrombin thrombin clot fibrinogen fibrin

  28. Anti-Clotting clot 1 cascade inhibition • TFPI • ATIII • Proteins C, S 2 clot lysis

  29. Anti-Clotting clot plasminogen plasmin t-PA

  30. Hemostasis Outline • The big picture • Laboratory tests

  31. Platelet Lab Tests Count • Done by particle counter • 150 – 450 x 109/L Morphology • Size • Granulation

  32. Platelets

  33. Normal Platelets

  34. Bleeding Time Why? • Evaluate platelet response to vascular injury • Some platelet disorders have a long bleeding time How? • Inflate blood pressure cuff • Make incision • Time how long it takes to stop bleeding Careful! • Lots of things affect the test! • Some consider the test unreliable.

  35. Coagulation Lab Tests • Draw blood into citrate tube • Spin tube, decant plasma • Add reagents to plasma • Watch for formation of fibrin

  36. Prothrombin Time • Plasma + thromboplastin • Measures extrinsic pathway

  37. SEXtrinsic Intrinsic TF VII IX VIII X V thrombin fibrin clot

  38. Extrinsic Intrinsic TF VII IX VIII X V The PT is increased in: •  VII, X, V, II, I • Coumadin • Heparin • DIC thrombin fibrin clot

  39. When should you order a PT? • Never! • Order an INR instead.

  40. What is an INR? Just a corrected PT.

  41. When should you order an INR? • To assess liver function • To monitor Coumadin therapy • To diagnose DIC* • To assess pre-op status * Disseminated intravascular coagulation

  42. Partial Thromboplastin Time • Plasma + phospholipid • Measures intrinsic pathway • APTT = same thing

  43. SINtrinsic Extrinsic TF VII IX VIII X V thrombin fibrin clot

  44. Extrinsic Intrinsic TF VII IX VIII X V The PTT is increased in: • hemophilia A • hemophilia B • DIC • heparin thrombin fibrin clot

  45. When should you order a PTT? • To investigate a history of abnormal bleeding • To monitor heparin therapy • To diagnose DIC • To assess pre-op status

  46. Fibrin Degradation Product Assay • Measures FDPs (including D-dimers) • VERY sensitive!

  47. Anti-Clotting clot

  48. Thrombin XIII cross-linked fibrin fibrinogen fibrin

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