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L15 b bleeding disorders my lecture (2)

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L15 b bleeding disorders my lecture (2)

  1. 1. Laboratory Tests forHaemostatic Functions Dr. Mohamed Iqbal Musani, MD
  2. 2. Hemostasis: BV Injury Tissue Neural Factor Blood Vessel Platelet Coagulation Constriction Activation Activation Primary hemostatic plug Reduced Plt-Fusion Thromibn, Blood flow Fibrin Stable Hemostatic Plug
  3. 3. Coagulation:Intrinsic 12,11,9,8 Extrinsic-7 (aPTT-) (PT) Common Path (TT) FX  FXa Prothrombin Thrombin Fibrinogen  Fibrin
  4. 4. Clot formation & retraction FibrinogenThrombin Fibrin Mononer Fibrin PolymerF-XIIIa Cross Linked Fibrin
  5. 5. Process- primary haemostasis In a normal individual, coagulation is initiated within 20 seconds after an injury occurs to the blood vessel damaging the endothelial cells. Platelets immediately form a haemostatic plug at the site of injury. This is called primary haemostasis.
  6. 6. Secondary haemostasis Secondary haemostasis then follows—plasma components called coagulation factors respond (in a complex cascade) to form fibrin strands which strengthen the platelet plug. Contrary to popular belief, coagulation from a cut on the skin is not initiated by air or drying out, but by platelets adhering to and activated by collagen in the blood vessel endothelium. The activated platelets then release the contents of their granules, these contain a variety of substances that stimulate further platelet activation and enhance the haemostatic process.
  7. 7. Coagulation cascade The coagulation cascade of secondary hemostasis has two pathways, the Contact Activation pathway (formerly known as the Intrinsic Pathway) And the Tissue Factor pathway (formerly known as the Extrinsic pathway) that lead to fibrin formation. It was previously thought that the coagulation cascade consisted of two pathways of equal importance joined to a common pathway. It is now known that the primary pathway for the initiation of blood coagulation is the Tissue Factor pathway. The pathways are a series of reactions, in which a zymogen (inactive enzyme precursor) of a serine protease and its glycoprotein co-factor are activated to become active components that then catalyze the next reaction in the cascade
  8. 8. Prothrombin Xa Va ThrombinFibrinogen Fibrin
  9. 9. Extrinsic Pathway TF Prothrombin VIIa Xa Va ThrombinFibrinogen Fibrin
  10. 10. Intrinsic pathway XIIa Extrinsic Pathway XIa TF Prothrombin IXa VIIa VIIIa Xa Va Thrombin Fibrinogen Fibrin
  11. 11. Intrinsic pathway XIIa Extrinsic Pathway XIa TF Prothrombin IXa VIIa VIIIa Xa Va Soft clot Thrombin Fibrinogen Fibrin XIIIa Hard clot Fibrin
  12. 12. Platelets: Bone marrow – Megakaryocytes – Life span 7-10d, N.count – 150-400x109/l 36 hours in spleen - 1/3 of plt in spleen Functions:  Hemostatic plug formation  Coagulation factors - release, synthesis Surface binding sites for fibrinogen, VWF Surface platelet antigens, HPA1
  13. 13.  I (fibrinogen II (prothrombin) Tissue factor Calcium V (proaccelerin, labile factor) VI VII (stable factor) VIII (antihemophilic factor) IX (Christmas factor) X (Stuart-Prower factor) XI (plasma thromboplastin antecedent) XII (Hageman factor) XIII (fibrin-stabilizing factor) von Willebrand factor
  14. 14. Tests of Hemostasis: Screening tests: tests  Bleeding.T - To test Platelet & BV function  Prothrombin.T – Extrinsic, aPTT – Instrinsic  Thrombin.T – Both paths. (DIC) Specific tests: tests  Factor assays –  Tests of thrombosis – TT, FDP, DDA,  Platelet function studies:  Adhesion, Aggregation, Release & PG pathway tests.  Bone Marrow study
  15. 15. Summary Complex system to keep blood fluid To block leakage on injury. BV, PLT & Coagulation Complex inhibitory mechanisms Complex thrombolysis mechanisms. Screening tests: BT, CT (PT, aPTT) Special tests: Factor assay, PLT function etc.
  16. 16. Disorders of Hemostasis Vascular disorders –  Scurvy, easy bruising, Henoch-Schonlein purpura. Platelet disorders  Quantitative - Thrombocytopenia  Qualitative - Platelet function disorders – Glanzmans Coagulation disorders  Congenital - Haemophilia (A, B), Von-Willebrands  Acquired - Vitamin-K deficiency, Liver disease Mixed/Consumption: DIC

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