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Hemostasis and Blood Coagulation
Prepared by Hamad ALAssaf 2015
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Hemostasis, Coagulation
1. Vascular Spasm 2. Platelet plug 3. Formation of clot
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Platelets - Sequestered in spleen (30%)
- Formed in bone marrow, ,000 /µl - Sequestered in spleen (30%) - 2-4 m in diameter, life span 8-12 days, no nucleus
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Platelets
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Clot Formation
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Formation of a Clot Intrinsic Surface Contact TF (Tissue factor)
XII-----XIIa Extrinsic XI-----XIa Tissue Damage TF-VIIa TF IX-----IXa VII X Xa X VIII VIIIa XIII Prothrombin Thrombin XIIIa Stable Fibrin Fibrinogen Fibrin Common
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Extrinsic Pathway
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Intrinsic Pathway
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Fibrinolytic System Plasminogen = circulating globulin
- Plasmin = proteolytic enzyme, similar to trypsin - digest fibrin threads, fibrinogen, and other clotting factors - Significance: removal of tiny little clots Plasminogen activators: - Tissue Plasminogen Activator (TPA), urokinase, streptokinase Plasminogen inhibitors: - plasminogen activator inhibitor (PAI-1) inhibits TPA - Alpha2-antiplasmin blocks binding plasminogen to fibrin
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Coagulation Defects I. Vitamin C deficiency: lack of stable collagen (elderly, alcoholics) collagen synthesis when dysfunctional, cause the most severe symptoms of scurvy. (Prevent healing of rupture capillaries). II. Hepatic failure: almost all clotting factors are made in the liver III. Vitamin K deficiency: - required for II (prothrombin), VII, IX, and X - fat malabsorption due to lack of bile secretion IV. Hemophilia: - Factor VIII (hemophilia A 1/10,000), - Factor IX (hemophilia B 1/100,000) - chromosome X
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Coagulation Defects V. Thrombocytopenia:
- bleeding small capillaries and blood vessels (mucosal, skin) - low number of platelets - Purpura- autoimmune (common) VI. Disseminated Intravascular Clotting: - abnormal bleeding and clot formation - critically ill patients - coagulation and clot lysis in uncontrolled manner - due to massive tissue damage - depletion of clotting factors
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Anti Coagulation HEPARIN ( iv or subcutaneous):
Used for Thromboembolic conditions such as : - Venous thrombosis, pulmonary embolism - artificial heart valves, by-pass surgery - long-term bed immobilization HEPARIN ( iv or subcutaneous): immediate anticoagulation It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism. Prolong PTT COUMARINS (e.g. warfarin given orally ): compete Vitamin K 2 - 4 days to act reverse coagulation. Prolong PT
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Blood Coagulation Tests
Platelet count: ,000/ µl - thrombocytopenia - aplastic anemia, autoimmune, platelet function myeloproliferative, uremia, drugs (aspirin, antibiotics), von Willebrand Disease Bleeding Time: - time for skin wound to stop bleeding - normal value < 6 minutes - done to assess platelets function. Clotting Time: - the time required for blood to form a clot - Normal value of clotting time is 2 to 6 minutes. - used to diagnose hemophilia Thrombin Time: - to evaluate the level and function of fibrinogen. - Normal values are 12 to 14 seconds.
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Tests of Clotting Pathway
XII Intrinsic Extrinsic XI Activated Partial Thromboplastin Time Prothrombin Time IX VII aPTT About 25 – 39 seconds VIII PT About 12 seconds The PTT is used to evaluate the coagulation factors XII, XI, IX, VIII, X, V, II (prothrombin) and I (fibrinogen). X PT test evaluates the coagulation factors VII, X, V, II, and I (fibrinogen). V Prothrombin (II) Thrombin
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Common condition present
PT result PTT result Common condition present Prolonged Normal Liver disease, decreased vitamin K, decreased or defective factor VII. Hemophilia A or B (decreased or defective factor VIII or IX) or factor XI deficiency, von Willebrand disease, factor XII deficiency, or lupus anticoagulant present. Decreased or defective factor I (fibrinogen), II (prothrombin), V or X, severe liver disease, disseminated intravascular coagulation (DIC). indicate normal hemostasis. Partial Thromboplastin Time (PTT) is a performance indicator of the efficacy of both the "intrinsic" and the common coagulation pathways. Prothrombin Time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway.
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