HAEMOSTASIS.pptx

Mechanism of normal hemostasis

1. HEMOSTASIS Mithun Venugopal. A MSc MLT Hematology and TRANSFUSION MEDICINE

2. What is hemostasis? Haem – blood Stasis – halt/hold Host defense mechanism, that protects the integrity of vascular system after tissue injury. It is a process of forming a barrier to the blood loss at the injured site.

3. stages Primary haemostasis: Platelet plug formation. Secondary haemostasis: Activation of coagulation cascade, deposition and stabilization of fibrin. Fibrinolysis: Degradation of fibrin clot.

4. Fibrin is formed by a series of complex biochemical reactions from soluble plasma proteins called clotting factors associated with injured blood vessel and platelet plug. All phases are controlled by inhibitors.

5. Components Vascular endothelium Platelets Coagulation FACTORS Fibrinolytic proteins

6. BV Injury Platelet Activation Platelet Fusion Blood Vessel Constriction Coagulation Activation Stable Hemostatic Plug Thromibn,Fibrin Reduced Blood flow Tissue Factor Neural

7. Vascular endothelium

8. Surface of endothelium is negatively charged and repels circulating platelets and proteins which are also negatively charged. Substances synthesized by endothelial cells LIKE heparan sulfate AND thrombomodulin inhibits THE thrombin formation). normally,

9. In endothelial injury, Platelets and coagulation factors are exposed to sub endothelial tissue. Interaction of vessel wall component and plasma components. Results in the formation of hemostatic plug

10. NORMAL IN ENDOTHELIAL INJURY

11. Vascular Component Vasoconstriction: Constriction of blood vessel to minimize the blood flow. Caused by , - Some neurogenic factors - Regulatory molecule (serotonin, thromboxane) produced by platelet activation - Endothelin by endothelial cells. Increased vascular permeability : Endothelial contraction produce gaps through which plasma leaks out into tissue causing edema/swelling.

12. Tissue thromboplastin : Released during injury. Helps in the formation of fibrin for secondary hemostasis. Von- willebrands factor: Produced by endothelium. Secreted into the plasma and into the sub endothelium. It binds with the collagen fibres in the extracellular matrix and supports the binding of platelet.

13. vWF Resting Platelets Platelet Adhesion

14. Vessel Wall Exposed collagen Contraction V FW Tissue TPL Platelet adhesion Activation of Coagulation Platelet Aggregation Thrombin 1◦ Hemostatic Plug Definitive Hemostatic Plug

15. Platelet Components

16. Platelet granules : Alpha granules vWF Fibrinogen PF4 Beta thromboglobulin Dense granules (delta) ADP Serotonin

17. PLATELET PRODUCTION THROMBOPOIESIS/MEGAKARYOPOIESIS : Generation of platelets. From megakaryocyte in bonemarrow. Controlled by thrombopoietin. Normal life span: 7-14 days

18. Role of platelets Injury – platelet react – primary hemostatic platelet plug – bleeding stops. Phospholipids (Aggregated platelet) – reaction surface for the formation of fibrin. Secretion from platelet helps to heal the injured site.

19. Steps: When injured, the inactive platelet become active and form primary platelet plug by various mechanisms like; a) Adhesion b) Activation c) Aggregation d) Secretion

20. Adhesion First step of primary hemostatic plug formation. During injury, platelet escapes from blood vessel and attaches to sub endothelium. vWF (sub endothelium) – gp-1b (platelet) vWF forms a bridge connecting platelet to endothelium.

21. Attachment of many platelets over the surface forms a monolayer. Cover the injured site. Bernard soulier syndrome – lack of gp 1b vWD disease – lack of vWF

22. Activation Adhesion triggers a series of morphologic and functional changes known as activation. Changes: Metabolic or biochemical. Due to substances produced by platelet or injured endothelium. AgonistS – agents induces platelet activation. Each agonist binds to a specific platelet receptor. It causes a series of reactions inside the platelet. Results in the changes in platelet shape (pseudopods are formed).

23. Increases the surface area of platelet. Platelet to platelet adherence increases. Platelet fit together. Activation also results in the formation of gp -IIb or GP-IIIa for fibrinogen binding. Receptors are hidden in resting platelets. Activation changes the membrane surface which allows fibrin forming protein (coagulation factors) to bind to it – platelet procoagulant activity.

24. Aggregation Attachment of platelet to one another. Free flowing platelets are also attached to the platelets that are adhere to the collagen. 2 types, 1. primary aggregation: adhere loosely to one another, reversible. 2. secondary aggregation: takes longer period, begin when platelet start producing their own agonist. Fibrinogen and calcium required for aggregation (released by platelet). Fibrinogen forms bridge between adjacent platelets.

25. Secretion Discharge of platelets granule contents into surrounding area (ADP, ATP, serotonin, thrombospondin, etc.) The released substances are agonists that stimulate platelet membrane receptors. Also increases the internal calcium level.

26. Primary hemostatic plug Eventually platelet form a barrier that seals the injury – 1◦ hemostatic plug. Unstable and easily dislodged. Stabilized by 2◦ hemostasis. 2◦ hemostasis starts with fibrin formation around the platelet plug.

27. SECONDARY HEMOSTASIS Occurs when soluble plasma protein (coagulation factors) interact in a series of complex enzymatic reactions to convert soluble fibrinogen to insoluble fibrin. Reactions occurs in a cascade. Each factor first act as a substrate and then an enzyme. Final substrate is fibrinogen acted upon by the final enzyme thrombin to form fibrin.

28. COAGULATION FACTORS Designated as roman numbers. I – XIII according to the order of discovery and not by reaction sequence. Factor VI is no longer included in the cascade as it is an activated form of factor V. Activated factor – letter ‘a’ accompanied the roman number.

29. (labile factor)

30. Pathways Intrinsic pathway: Contact of CF with negatively charged surface. Extrinsic pathway: Contact of CF VII with tissue factor. Common pathway

31. FIBRINOLYSIS PLASMINOGEN PLASMIN ACTIVATORS Urokinase Streptokinase kallikrein FIBRIN FDP Anti plasmin macroglobulin INHIBITORS PAI 1 PAI 2 PAI 3

32. REFERENCE Sherlyn B Mckenzie

33. QUESTIONS???

34. THANK YOU…