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Blood coagulation

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postgraduate surgery presentation

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Blood coagulation

  1. 1. BLOOD COAGULATION PRESENTER: DR PASHI V MODERATOR: DR ZULU R
  2. 2. SCOPE • HAEMOSTASIS OVERVIEW • PLATELETS • PLATELET PLUG FORMATION • BLOOD COAGULATION • HEMOSTATIC FUNCTION TESTS • DISORDERS OF COAGULATION • ANTICOAGULANTS
  3. 3. HEMOSTASIS OVERVIEW • DEFINITION - Heme = blood - stasis = to halt • It is the process of forming clots in the wall of damaged blood vessels & preventing blood loss while maintaining blood in a fluid state with in the vascular system. • Spontaneous arrest of bleeding by physiological process.
  4. 4. 4 Mechanism Haemostasis involves 4 main steps: 1. Vascular spasm 2. Platelets reaction 3. Formation of platelet plug 4. Blood coagulation
  5. 5. 5 I-Vascular spasm Reduces flow of blood from injured vessel. Cause: 1- Sympathetic reflex 2- Release of vasoconstrictors (TXA2 and serotonin) from platelets that adhere to the walls of damaged vessels.
  6. 6. 7 II- Platelet plug formation Mechanism: Platelet adherence Platelet activation Platelet aggregation
  7. 7. platelet adhesion
  8. 8. platelet adhesion
  9. 9. Platelet activation : platelet release action
  10. 10. Platelet aggregation
  11. 11. 12 Platelets • Produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes (1000-5000/cell). • 1/3 of marrow output of platelets is trapped in spleen (splenectomy?) • Normal count: 150,000-400,000/µL (250,000) • Life span 7-10 days. • Removed from circulation by tissue macrophage system mainly in spleen. • Thrombopoietin: major regulator of platelet production (produced by liver and kidney). • It increases no. & rate of maturation of megakaryocytes.
  12. 12. 13 Functional characteristics of platelets • The cell membrane of platelets contains: – A coat of glycoprotein (receptors) that cause adherence to injured endothelial cells and exposed collagen. – Phospholipids, that play an important role in blood clotting.
  13. 13. • Membrane • Outer glycocalyx layer— glycoproteins • Inner lipoprotein layer— phospholipid
  14. 14. 15 • Their cytoplasm :  Contains:  contractile proteins (actin & myosin).  Dense granules, which contain substances that are secreted in response to platelet activation including serotonin & ADP.  α-granules, which contain secreted proteins e.g. platelet-derived growth factor (PDGF) which stimulates wound healing, fibrin stabilizing factor (factor XIII) and other clotting factors.  Can store large quantities of Ca++.
  15. 15. platelet adhesion
  16. 16. 17 Mechanism of platelet plug formation * Platelet adhesion: When a blood vessel wall is injured, platelets adhere to the exposed collagen and von Willebrand factor in the wall via platelet receptors → Platelet activation. *Activated platelets release the contents of their granules including ADP and secrete TXA2 → activates nearby platelets to produce further accumulation of more platelets (platelet aggregation) and forming a platelet plug.
  17. 17. 181818
  18. 18. 19
  19. 19. Secondary hemostasis • “Cascade of reactions” by Macfarlane, R.G.,1967 It states that ‘inactive’ enzymes are activated, and the ‘activated’ enzymes in turn activates other inactive enzymes until final step is reached.
  20. 20. 21 Blood Coagulation The clotting mechanism involves a cascade of reactions in which clotting factors are activated. Most of them are plasma proteins synthesized by the liver (vitamin K is needed for the synthesis of factor II, VII, IX and X). They are always present in the plasma in an inactive form. When activated they act as proteolytic enzymes which activate other inactive enzymes. Several of these steps require Ca++ and platelet phospholipid.
  21. 21. ENZYME CASCADE SEQUENCE STAGE 1: FORMATION OF PROTHROMBIN ACTIVATOR STAGE 2: CONVERSION OF PROTHROMBIN INTO THROMBIN STAGE3: CONVERSION OF FIBRINOGEN INTO FIBRIN
  22. 22. 25 Blood Coagulation • The ultimate step in clot formation is the conversion of fibrinogen → fibrin.
  23. 23. Factor X can be activated by reactions in either of 2 systems: An Intrinsic system. An Extrinsic system 26
  24. 24. 27 Intrinsic pathway The initial reaction is the conversion of inactive factor XII to active factor XIIa. Factor XII is activated in vitro by exposing blood to foreign surface (glass test tube). Activation in vivo occurs when blood is exposed to collagen fibers underlying the endothelium in the blood vessels.
  25. 25. 2nd Year Physiotherapy- November 2008 28
  26. 26. 29 Extrinsic pathway Requires contact with tissue factors external to blood. This occurs when there is trauma to the vascular wall and surrounding tissues. The extrinsic system is triggered by the release of tissue factor (thromboplastin from damaged tissue), that activates factor VII. The tissue thromboplastin and factor VII activate factor X.
  27. 27. Extrinsic Pathway
  28. 28. 31 Clot retraction Clot formation is fully developed in 3-6 min Contraction of platelets trapped within the clot shrinks the fibrin meshwork pulling the edges of the damaged vessel closer together. During clot retraction serum is squeezed from the clot.
  29. 29. • Release of fibrin stabilizing factor • Contractile protein of platelets • Activated and accelerated by thrombin and Ca ions.
  30. 30. WHY BLOOD DOES NOT CLOT IN CIRCULATION ? • Endothelial surface factor -smoothness -layer of glycocalyx -Negatively charged • Velocity of circulation • Natural anticoagulants • Activation of Fibrinolytic system • Liver removes activated clotting factors
  31. 31. METHOD OF STUDY • HEMOSTATIC FUNCTION TESTS -Bleeding time -Clotting time -Prothrombin time
  32. 32. BLEEDING TIME (B.T) Definition ; - time interval between the skin puncture and spontaneous , unassisted stoppage of bleeding. Method ; “Duke’s method” Other methods ; “ivy” Bleeding time Normal bleeding time ; 1 – 5 min. 35
  33. 33. CLOTTING TIME ( C.T )  Definition ; - time interval between entry of blood into glass capillary tube, or a syringe, and formation of fibrin threads.  Method ; Wright’s capillary glass tube  Other Methods ; Duke’s Drop method, Lee and White test- tube method  Normal Clotting Time ; 3 – 6 min.
  34. 34. PROTHROMBIN TIME (P.T) Normal P.T ; 15 – 20 sec. Clinical Significance ; bleeding tendency occurs below 20% (Normal plasma prothrombin = 30- 40 mg/dl) Low prothrombin suggest Vit. K def. and liver and biliary diseases. Prolonged suggests deficiency of factor II, V, VII, and X. 37
  35. 35. INR • A PT test may also be called an INR test. • INR (international normalized ratio) stands for a way of standardizing the results of prothrombin time tests. • Normal is 0.9 – 1.3 but therapeutic values ranges from 2.0 – 4.0
  36. 36. • An INR of 1.0 means that the patient PT is normal. • An INR greater than 1.0 means the clotting time is elevated. • INR of greater than 5 or 5.5 = unacceptable high risk of bleeding, whereas if the INR=0.5 then there is a high chance of having a clot. • Normal range for a healthy person is 0.9–1.3, and for people on warfarin therapy, 2.0–3.0, although the target INR may be higher in particular situations, such as for those with a mechanical heart valve.
  37. 37. DISORDERS OF COAGULATION • Defective blood clotting - deficiency of clotting factors (I, II, V, VIII, IX, X) - deficiency of Vit- K -von Willebrand disease - anticoagulant overdose • Defective capillary contractility - Purpura • Thrombosis
  38. 38. DEFICIENCY OF FACTORS
  39. 39. Hemophilia – B ( Christmas disease) Factor – IX deficiency
  40. 40. Hemophilia - C Factor – XI (Plasma thromboplastin anticedent) deficiency.
  41. 41. Hemophilia - D Factor – XII ( Hageman factor) deficiency 44
  42. 42. Hemophilia • Factor – VIII deficiency • Inheritance – Sex linked, -X-chromosome, females are carrier • Diagnosis - CT increased, BT- normal • Treatment - Fresh blood transfusion - Injecting factor – VIII and IX - Injecting thrombin or thromboplastin
  43. 43. Purpura • Purple coloured petechial hemorrhages and bruises in the skin. • Characterized by spontaneous hemorrhages beneath the skin, mucous membrane and internal organ. • Capillary abnormality • Types - Primary (Idiopathic) –congenital or heriditary , seen in children - Secondary (Symptomatic) - allergies, infections, drugs, cancer
  44. 44. • VON WILLEBRAND’S DISEASE • Deficiency of VWF & amount of Factor VIII • Factor VIII is bound to vWF while inactive in circulation; Factor VIII degrades rapidly when not bound to vWF • Lab Results - Prolonged BT, PTT
  45. 45. Name the conditions where bleeding time is prolonged and clotting time is normal ?  1. Low platelet count  2.Functional platelet defect ; i.Drugs : aspirin, large dose of penicilin ii.von Willebrand disease iii.others : uremia, cirrohosis, leukemia  3. Vessel wall defects ; i. Prolonged corticosteroid trt. ii. Allergic purpura iii. Infections : typhus, bacterial endocarditis iv. Deficiency of Vit – C v. Connective tissue diseases
  46. 46. Name the conditions where clotting time is prolonged and bleeding time is normal ?  1. Hereditary coagulation disorders i. Hemophilias ii. von Willebrand disease iii. Afibrinogenemia or dysfibrinogenemia  2. Acquired Coagulation disorders i. Vit – K def. ii. Liver disease iii. Intravascular clotting iv. Anticoagulant therapy  3. Newborns
  47. 47. ANTICOAGULANTS  Natural Anticoagulants  Heparin  Antithrombin or Heparin co-factors  Protein C
  48. 48. Heparin • Potent Anticoagulant • First isolated from liver • Polysaccharide, MW- 15000-18000 • Facilitates action of antithrombin-III • Inhibits active form of IX, X, XI, and XII • Origin - granules of basophils - mast cells contains IgE (Reagin), heparin, histamine, aid in defecnc mechanism • Destruction – Heparinase in liver • Uses - maintains fluidity of blood, - prevention of post-operative intravascular coagulation
  49. 49. Synthetic Anticoagulant  Vitamin K Antagonist i. Coumarin derivatives – Dicumarol ii. Warfarin iii. Phenindione iv. Nicoumalone  Removing Ca2+ from blood - Sodium citrate, sodium oxalate, sod. Edeate (EDTA)  Snake Venom - fibrinogenopenia  Cold - 5-100C
  50. 50. REFFERENCES • Barret, K.E, etal(2010), Ganong’s Review of Medical Physiology, 23rd edition, McGraw Company, USA • Raftery, A.T(2008), Applied Basic Science for Basic Surgical Training, 2nd edition, Elsevier, USA. • Guyton AC, Hall JE : Textbook of Medical Physiology, 11th Edition, Elsevier Saunders, 2006

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