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PT APTT Technical Information


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PT APTT Technical Information

  1. 1. PT & aPTT Manish Pandey
  2. 2. Hemostasis Is a Balance Between Clot Formation & Clot Dissolution.
  3. 3. Normal Hemostasis Clot formation (Coagulation) Clot dissolution (Fibrinolysis) PT aPTT Thrombin Time Fibrinogen Individual factor tests FDP D-Dimer vWF HMWK Prekallikrein
  4. 4. Thrombosis <ul><li>Abnormal Hemostasis is Thrombosis </li></ul><ul><li>Formation of Blood Clot ( thrombus) in normal blood vessels </li></ul><ul><li>Thrombotic occlusion of a vessel after relatively minor injury </li></ul>
  5. 5. Hemostasis involves the interaction of: <ul><li>Vascular Endothelium </li></ul><ul><li>Platelets </li></ul><ul><li>Coagulation Factors and </li></ul><ul><li>Fibrinolytic Proteins </li></ul>
  6. 6. <ul><li>Hemostasis has 2 main functions: </li></ul><ul><li>Induce a rapid & localized hemostatic plug at the site of vascular injury (clot formation) </li></ul><ul><li>Maintain Blood in a fluid, clot-free state after the injury is healed (clot dissolution) </li></ul>
  7. 8. Primary Hemostasis <ul><li>Injury </li></ul><ul><li>Endothelial Cells </li></ul><ul><li>Exposure of thrombogenic surface (subendothelial extracellular matrix) </li></ul>
  8. 9. <ul><li>Platelets adhere and get activated </li></ul><ul><li>Change shape </li></ul><ul><li>Release secretory granules </li></ul><ul><li>(e.g. ADP, TXA2) </li></ul><ul><li>Attract other platelets and Aggregate </li></ul><ul><li>Hemostatic plug or Primary Platelet Plug </li></ul>
  9. 10. Secondary Hemostasis <ul><li>Fibrin is required to stabilize the primary platelet plug </li></ul><ul><li>Fibrin is formed by two coagulation pathways i.e. Extrinsic & Intrinsic </li></ul><ul><li>Extrinsic Pathway is initiated when Tissue Factor (III) present in damaged organ comes in contact with Blood </li></ul><ul><li>Intrinsic Pathway is initiated when Factor XII binds to a negatively charged “foreign” surface exposed to Blood </li></ul>
  10. 11. Coagulation Factors Both Calcium IV Pathway Trivial Name Factor Extrinsic Tissue Factor III Both Prothrombin II Both Fibrinogen I Intrinsic Contact activation cofactor HMWK Intrinsic Fletcher factor Prekallikrein
  11. 12. Intrinsic Antihemophilic factor B XI Intrinsic Antihemophilic factor A VIII Extrinsic Proconvertin VII Both Accelerin VI (Va) Both Proaccelerin, Labile factor V
  12. 13. Both Fibrin Stabilizing factor XIII Intrinsic Hageman Factor XII
  13. 17. PT and aPTT testing <ul><li>PT ( Prothrombin Time) test is done for deficiency of factors of extrinsic pathway </li></ul><ul><li>aPTT ( activated Partial Thromboplastin Time) test is done for deficiency of factors of Intrinsic pathway </li></ul>
  14. 18. Effects of Hereditary or Acquired Factor Deficiency on the PT & aPTT <ul><li>aPTT prolonged, PT normal </li></ul><ul><li>Deficiencies of intrinsic pathway Factor(s) VIII, IX, XI or XII </li></ul><ul><li>PT prolonged, aPTT normal </li></ul><ul><li>Deficiency of extrinsic Pathway factor VII </li></ul><ul><li>Occasionally, mild to moderate deficiency of common pathway factor(s) fibrinogen, II, V or x </li></ul>
  15. 19. <ul><li>Both PT and aPTT Prolonged </li></ul><ul><li>Deficiency of common pathway factor(s) fibrinogen, II, V, or X </li></ul><ul><li>Multiple factor deficiencies </li></ul>
  16. 20. Mixing studies in PT PT mixing study (1:1 mix of patient and normal plasma PT normalizes Factor Deficiency; Measure factors I, II, V, VII, X PT initially shortens and then prolongs Factor V inhibitor (rare) aPTT remains prolonged Inhibitor (specific factor inhibitor, rare) Treat specimen with heparinase (degrades heparin) PT normal, prolongation due to heparin PT prolonged
  17. 21. Mixing studies in aPTT aPTT mixing study (1:1 mix of patient and normal plasma aPTT normalizes Factor Deficiency; Measure factors VIII, IX, XI, XII aPTT initially shortens and then prolongs Factor VIII inhibitor aPTT remains prolonged Inhibitor, most commonly Lupus Anticoagulant Treat specimen with heparinase (degrades heparin) aPTT normal, prolongation due to heparin aPTT prolonged
  18. 23. Fibrinolytic Mechanism <ul><li>Stable Fibrin Clot </li></ul><ul><li>Activation of Protein C and Protein S </li></ul><ul><li>Secretion of t-PA by endothelial cells </li></ul><ul><li>Plasminogen Plasmin </li></ul><ul><li>Stabilized fibrin clot </li></ul><ul><li>X, Y fragments </li></ul><ul><li>Plasmin Degrades D-E-D fragments </li></ul><ul><li>E fragment + D dimer </li></ul>
  19. 24. Fibrinolysis <ul><li>As soon as the injury is healed clot dissolution starts, to restore the normal flow of Blood </li></ul><ul><li>Plasminogen is converted to the active form Plasmin by 2 distinct Plasminogen Activators (PAs): </li></ul><ul><li>tissue plasminogen activator (t-PA) from injured endothelial cells </li></ul><ul><li>Urokinase from Kidney endothelial cells and plasma </li></ul>
  20. 25. Fibrinolysis <ul><li>or Kallikrein from Intrinsic Pathway </li></ul><ul><li>Plasminogen can also be activated by the bacterial product (e.g. Streptokinase) – having significance in certain Bacterial Infections </li></ul><ul><li>Free Plasmin is neutralized by α 2- plasmin inhibitor (PAI) </li></ul><ul><li>t-PA activity is also blocked by PAI </li></ul>
  21. 26. <ul><li>Endothelial cells modulate the coagulation / anticoagulation balance by releasing PAIs </li></ul><ul><li>PAIs block fibrinolysis by inhibiting t-PA binding to fibrin as it is most active when bound to fibrin </li></ul>
  22. 27. Fibrinolysis <ul><li>Three types of Natural Anti-coagulants regulate clotting: </li></ul><ul><li>antithrombin III – inhibit thrombin activity and Factors IXa, Xa, XIa and XIIa </li></ul><ul><li>Protein C and Protein S – Vitamin K dependent proteins, inactivate Factors Va and VIIIa </li></ul><ul><li>Plasmin </li></ul>
  23. 28. <ul><li>Fibrin Degradation Products or FDP’s include: </li></ul><ul><li>fragments X and Y – early splits and </li></ul><ul><li>D and E – late splits </li></ul><ul><li>D-Dimer is the smallest cross-linked FDP </li></ul>
  24. 29. <ul><li>D-Dimer are specific FDP formed only by Plasmin activity on fibrin clot and not on intact fibrinogen </li></ul><ul><li>Thus the presence of D-Dimer indicates that fibrin has been formed and so is a marker for an ongoing in vivo thrombotic condition </li></ul>
  25. 30. Clinical Significance of Hemostasis <ul><li>Hemophilia A: Caused by the deficiency of Factor VIII </li></ul><ul><li>Hemophilia B: Caused by the deficiency of Factor IX </li></ul><ul><li>Vitamin K deficiency </li></ul><ul><li>(PIVKA’s) P rotein I nduced V itamin K A ntagonism can be used in thrombotic conditions </li></ul><ul><li>Vitamin K dependent factors are </li></ul><ul><li>II, V, IX, & X </li></ul>
  26. 31. <ul><li>Liver Dysfunction </li></ul><ul><li>Fibrinogen and Factor XIII deficiency </li></ul><ul><li>Factor XI and Contact Activation </li></ul><ul><li>Antithrombin Deficiency leads to DVT and PE </li></ul><ul><li>von Willebrand Disease: Deficiency of von Willebrand Factor </li></ul>Clinical Significance of Hemostasis
  27. 32. DIC (Disseminated Intravascular Coagulation) <ul><li>Massive Injury or Sepsis </li></ul><ul><li>Massive release of Tissue Factor III </li></ul><ul><li>Excessive Activation of Thrombin </li></ul><ul><li>Coagulation becomes systemic </li></ul>
  28. 33. <ul><li>High consumption of Platelets, coagulation factors </li></ul><ul><li>Over production of fibrin clot </li></ul><ul><li>Fibrin clot “disseminates” or spreads throughout the microcirculation </li></ul><ul><li>Obstructing the blood flow to capillaries, smaller vessels </li></ul>
  29. 34. <ul><li>Lack of blood supply leads to tissue injury (decreased oxygenation, organ infarction & necrosis) </li></ul><ul><li>Once again release of Tissue Factor </li></ul><ul><li>Second time coagulation activation </li></ul><ul><li>More consumption of coagulation factors and platelets </li></ul>
  30. 35. <ul><li>Continuous thrombi formation </li></ul><ul><li>Production capacity of Bone Marrow and Liver reaches its maximum level </li></ul><ul><li>Activation of fibrinolysis at first site </li></ul><ul><li>High consumption of Plasmin, antithrombin, Protein C and Protein S </li></ul>
  31. 36. <ul><li>Generation of Thrombin & Plasmin at the same time </li></ul><ul><li>Plasmin acts on Fibrin Clots and produces FDPs and D-Dimer </li></ul><ul><li>FDPs interfere with platelet function and impair fibrin clot formation </li></ul><ul><li>Further bleeding results </li></ul>
  32. 37. <ul><li>Thus an initial thrombotic disorder gets converted into a serious bleeding disorder </li></ul><ul><li>Whenever there is a widespread activation of Thrombin the chances are that it may lead to DIC </li></ul>
  33. 38. Pharmacological Intervention <ul><li>Most commonly patients are on OAC (oral anti-coagulant) therapy: </li></ul><ul><li>warfarin – over dose can lead to Vit. K deficiency </li></ul><ul><li>heparin </li></ul><ul><li>Fibrinolysis: </li></ul><ul><li>Aspirin </li></ul><ul><li>Streptokinase, urokinase injections </li></ul><ul><li>t-PA injections </li></ul>
  34. 39. INR & ISI values <ul><li>All PT reagents are calibrated against WHO IRP (International Reference Preparation) </li></ul><ul><li>International Normalisation Ratio is intended to make comparison similar irrespective of the type of PT reagent used worldwide </li></ul><ul><li>International Sensitivity Index is a measure of the sensitivity of particular PT reagent </li></ul>
  35. 40. <ul><li>Insensitive PT reagents will give prolonged results only when factor levels are very low </li></ul><ul><li>Sensitive PT reagent give prolonged results even when there is a mild change in factor level </li></ul><ul><li>Insensitive PT reagents have higher ISI values </li></ul><ul><li>Sensitive PT reagents have ISI value as close to 1.0 as possible </li></ul>
  36. 41. Calculation of PT results <ul><li>INR = (Ratio) ISI </li></ul><ul><li>Patient PT Time (secs) </li></ul><ul><li>Mean Normal PT (MNPT) </li></ul><ul><li>MNPT = Mean PT Time of at least 20 known normal samples </li></ul>INR = ISI
  37. 42. Thanks <ul><li>Please send your feedbacks to: </li></ul><ul><li>Priyank Dubey </li></ul><ul><li>Ph: 09999990845 </li></ul><ul><li>[email_address] </li></ul><ul><li>Application Specialist </li></ul>