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L15 b bleeding disorders my lecture (2)
 

L15 b bleeding disorders my lecture (2)

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    L15 b bleeding disorders my lecture (2) L15 b bleeding disorders my lecture (2) Presentation Transcript

    • Laboratory Tests forHaemostatic Functions Dr. Mohamed Iqbal Musani, MD
    • 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
    • Coagulation:Intrinsic 12,11,9,8 Extrinsic-7 (aPTT-) (PT) Common Path (TT) FX  FXa Prothrombin Thrombin Fibrinogen  Fibrin
    • Clot formation & retraction FibrinogenThrombin Fibrin Mononer Fibrin PolymerF-XIIIa Cross Linked Fibrin
    • 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.
    • 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.
    • 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
    • Prothrombin Xa Va ThrombinFibrinogen Fibrin
    • Extrinsic Pathway TF Prothrombin VIIa Xa Va ThrombinFibrinogen Fibrin
    • Intrinsic pathway XIIa Extrinsic Pathway XIa TF Prothrombin IXa VIIa VIIIa Xa Va Thrombin Fibrinogen Fibrin
    • Intrinsic pathway XIIa Extrinsic Pathway XIa TF Prothrombin IXa VIIa VIIIa Xa Va Soft clot Thrombin Fibrinogen Fibrin XIIIa Hard clot Fibrin
    • 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
    •  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
    • 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
    • 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.
    • 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