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Blood Coagulation

Blood Coagulation. Haemostasis part1. Haima + Stasis. Prevent blood loss. Maintains blood flow. Prevents bleeding. Components of hemostasis. Interactive. Components: vascular. Intact endothelium: Non-thrombogenic. (-). (-). Components: platelets. Adhesion. Activation. Aggregation.

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Blood Coagulation

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  1. Blood Coagulation

  2. Haemostasispart1

  3. Haima + Stasis Prevent blood loss

  4. Maintains blood flow Prevents bleeding

  5. Components of hemostasis Interactive

  6. Components: vascular Intact endothelium: Non-thrombogenic (-) (-)

  7. Components: platelets Adhesion Activation Aggregation Secretion Procoagulant activity

  8. Components: coagulation pathways Pivotal point of coagulation Thrombin Intrinsic Extrinsic (TF) Amplification Initiation

  9. Primary haemostasis I: ● Capillaries and larger blood vessels react to injury by an immediate local temporary vasoconstriction (a reflex nervous mechanism) to reduce the amount of blood lost.

  10. Secundary haemostasis:Blood coagulation factors are necessary to stop bleeding definitely. • I: fibrinogen • II: prothrombin • III: tissue thromboplastin (tissue factor, TF) • IV: Ca++ • V: proaccelerin • VI: - • VII: proconvertin • VIII: antihemophilic factor (AHF) • IX: Christmas factor (plasma thromboplastin component) • X: Stuart factor • XI: plasma thromboplastin antecedent (PTA) • XII: Hageman factor (contact factor) • XIII: fibrin stabilizing factor (Laki-Lorand factor)

  11. 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.

  12. 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.

  13. 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

  14. Prothrombin Xa Va Thrombin Fibrinogen Fibrin

  15. Extrinsic Pathway TF Prothrombin VIIa Xa Va Thrombin Fibrinogen Fibrin

  16. Intrinsic pathway XIIa Extrinsic Pathway XIa TF Prothrombin IXa VIIa VIIIa Xa Va Thrombin Fibrinogen Fibrin

  17. Intrinsic pathway XIIa Extrinsic Pathway XIa TF Prothrombin IXa VIIa VIIIa Xa Va Soft clot Thrombin Fibrinogen Fibrin XIIIa Hard clot Fibrin

  18. Coagulation made easy The PTT Pathway The PT Pathway

  19. Coagulation made easy The PTT Pathway The PT Pathway X The PT and the PTT pathway meet at factor X, because “X” marks the spot

  20. Coagulation made easy The PTT Pathway The PT Pathway V X Factor V is a cofactor for factor X, and you can remember this because V fits into the notch of the X

  21. Prothrombin Thrombin Coagulation made easy The PTT Pathway The PT Pathway V X Factor Xa converts prothrombin (Factor II) into thrombin, the most important enzyme on the planet

  22. Prothrombin Fibrinogen Thrombin Fibrin Coagulation made easy The PTT Pathway The PT Pathway V X Thrombin, among other things, converts the soluble molecule fibrinogen into a solid fibrin clot

  23. Prothrombin Fibrinogen Thrombin Fibrin Coagulation made easy - the PT The PT Pathway PT has one less letter than PTT, and PT values are shorter than PTT values, because the pathway is shorter. It means that the PT pathway is also shorter and this is lucky, so the lucky PT pathway uses lucky factor 7 to activate factor X 7 V X

  24. Prothrombin Fibrinogen Thrombin Fibrin Coagulation made easy - the aPTT The PTT Pathway XII The PTT pathway has all those hideous roman numerals. . . How are we going to remember them? Hmmmmm. . . . . . . XI IX V X VIII

  25. Prothrombin Fibrinogen Thrombin Fibrin Coagulation made easy - the aPTT The PTT Pathway T Well, just remember that the PTT is a basic TENET of hematology. TENET stands for. . . . . . E N E V X T

  26. Prothrombin Fibrinogen Thrombin Fibrin Coagulation made easy - the aPTT The PTT Pathway Twelve Eleven Nine Eight V X Ten

  27. Coag Made Easy: PT and PTT both Prolonged The PTT Pathway The PT Pathway V X These factors are in the common pathway Prothrombin (II) Fibrinogen

  28. Coag Made Easy: Only PT Prolonged 7 Deficiency of Factor VII will prolong the PT but not the PTT

  29. Coag Made Easy: Only PTT Prolonged Deficiencies of Factors 12, 11, 9 and 8 will prolong the PTT and not the PT. Remember that factor 10 is in the common pathway, and affects BOTH the PT and the PTT Twelve Eleven Nine Eight Ten

  30. Platelet Adhesion mediated by GP-Ib on platelet surface and vWF fibrinogen C O L L A G E N C O L L A G E N GP-Ib von Willebrand Factor endothelial cells

  31. von Willebrand Factor • Synthesized & stored in endothelial cells and megakaryocytes (also stored in platelets) • Forming bridge between subendothelial collagen and Plt • Carrier molecule for Factor VIII Coagulant Protein (vWF is also known as Factor VIII Related Antigen) • Circulates as series of multimers (in various sizes) • Large, high molecular weight multimers required for normal hemostasis

  32. Platelet Activation release of a and electron dense granules • Release of platelet’s cytoplasmic products • activation of platelet factor III (PF-3) PF-3 serves as a binding site for cofactor V & VIII • production of thrombin C O L L A G E N GP-IIb, IIIa

  33. Platelet Aggregation GP IIb-IIIa - fibrinogen interaction • formation of primary plug • activated platelets synthesize and secrete TXA2 TXA2: 1. promotes plt aggregation 2. vasoconstriction 3. release of plt factor (ADP) C O L L A G E N Aspirin inhibits TXA2 and ADP

  34. Coagulation Factors negative charged surface • Intrinsic Pathway • Extrinsic Pathway • Common Pathway • majorities are serine proteases • circulate as inactive forms (require activation to function) • majority produced in liver XII XI tissue factor IX intrinsic pathway extrinsic pathway VIII VII X V PT aPTT II I XIII Stable clot

  35. Coagulation Factors negative charged surface • Intrinsic Pathway • Extrinsic Pathway • Common Pathway • majorities are serine proteases • circulate as inactive forms (require activation to function) • majority produced in liver • many require vit K for synthesis • II, VII, IX, X • protein C, S XII XI tissue factor IX intrinsic pathway extrinsic pathway VIII VII X V PT aPTT II I XIII Stable clot

  36. Newer Concepts of Coagulation Reactions 2 main functions of tissue factor (TF) 1) to activate factor X to Xa 2) to activate factor IX to IXa

  37. Control Mechanisms APC: activated protein C AT : antithrombin GAG: glycoaminoglycans T : thrombin PC : protein C S : protein S TF : tissue factor TM : thrombomodulin 1) TF pathway inhibitor 2) Protein C system 3) Antithrombin (e.g. AT III) 4) Glycoaminoglycans

  38. Platelet PLUG

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