Hemostsis & thrombosis

Hemostsis & thrombosis

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  Hemostsis & Thrombosis DrAlok Tripathi Department of Biotechnology
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  Hemostsis & Thrombosis:Definition • Hemostasis is result from well regulated process that maintain blood in a fluid clot free state in a normal vessel while inducing a rapid formation of localized hemostatic plug at the site of vascular injury. • haemostasis—the rapid arrest of blood loss upon vascular damage, in order to maintain a relatively constant blood volume. • The process by which blood is maintained in a fluid state and confined to the circulatory system Hemostasis • The formation of blood clot (Thrombus) in uninjured vessel. Or • Thrombotic occlusion of a vessel after a relatively minor injury. Thrombosis
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  Components of hemostasis Hemostasisis a complex process and actually comprises a number of distinct, but closely linked biochemical systems. The blood platelets are responsible for primary hemostasis and for providing the framework for subsequent coagulation and wound healing. Fibrinolysis is required for the removal of fibrin that is no longer needed and for the eventual remodeling of the injured area. All these systems are closely linked to inflammation, especially through contact activation of FXII. Platelets Coagulation Inflammation Wound healing HEMOSTASIS Fibrinolysis
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  Three phases ofhemostasis • Primary hemostasis ▫ formation of a platelet ‘plug’ • Secondary hemostasis ▫ consolidation of the platelet plug by fibrin • Fibrinolysis ▫ cleanup
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  Primary hemostasis activation inresponse to stimuli adherence to the margins of the lesion release of granule contents aggregation into a primary platelet plug
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  The platelet GpIb GpIIb/IIIa Dense granule Alpha granule Cell membrane Coagulation proteins
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  Fig. 1. Woundhealing is a complex process encompassing a number of overlapping phases, including inflammation, epithelialization, angiogenesis and matrix deposition. During inflammation, the formation of a blood clot re-establishes hemostasis and provides a provisional matrix for cell migration. Cytokines play an important role in the evolution of granulation tissue through recruitment of inflammatory leukocytes and stimulation of fibroblasts and epithelial cells. [Note: figure is adapted from reference 1.]
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  Normal Hemostasis: 1 GeneralSequence of Events are: Endothelial injury : it is also exposed highly thrmbogenic subendothelial extracellular matrix (ECM) which allow platelets to adhere and activated ie. a shape change Release of secretory granules Within a minute secretory product recruits several platelets to form hemostatic plug. Vasoconstriction : After a initial injury there is a brief period of arteriolar vasoconstriction due to Reflex neurogenic mechanism Local secretion of the factors such as endotheline
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  three main mechanismsunderline the haemostatic process The congregation and clumping of blood platelets at the site of vascular injury, thus effectively plugging the site of blood leakage. Localized constriction of the blood vessel, which minimizes further blood flow through the area. Induction of the blood coagulation cascade. This culminates in the conversion of a soluble serum protein, fibrinogen, into insoluble fibrin. Fibrin monomers then aggregate at the site of damage, thus forming a clot (thrombus), which seals it off. These mechanisms are effective in dealing with small vessel injuries, e.g. in capillaries and arterioles, although they are ineffective when the damage relates to large veins/arteries.
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  Normal Hemostasis:2 General Sequenceof Events are: Polymerized fibrin & platelet aggregates form a permanent plug to prevent any further hemorrhage Tissue Factors: a membrane bound procougulant factors is synthesized by the endothelium, also released at the site of injury. It act in conjugation with secreted platelet factor actor to activate the coagulation cascades in activation of thrombin In turn thrombin cleave fibrinogen into insoluble fibrine, creating a fibrin meshwork Thrombin also induced further platelet requirement & granules released.
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  Endothelium Modulate several aspect ofanti- cougulating properties Anti-platelet ,Anti- couagulent & fibrinolytic Exerts pro- couagulent functions It may activated by infectious agents, hemodynamic factors plasma mediators & CK
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  Antithrambic Properties • Anintact endothelium prevent platelets from meeting from highly thrmbogenic subendothelial ECM • Nonactivated platelet do not adhere endothelium an intrinsic property of endothelium. • If platelets are activated they are inhibited from adhering to surrounding uninjured endothelium by prostacyclin (PGI2) & Nitric oxide • Both mediators are potent vasodilators & Inhibitors of platelet aggregation. • Syntasis of PGI2 is stimulated by a no of factors eg CK, thrombin, thrombomoduline Antiplatelet effects
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  Vasoconstriction
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  Figure 51–8. Diagrammaticrepresentation of platelet activation. The external environment, the plasma membrane, and the inside of a platelet are depicted from top to bottom. Thrombin and collagen are the two most important platelet activators. ADP is considered a weak agonist; it causes aggregation but not granule release. (GP, glycoprotein; R1–R5, various receptors; AC, adenylyl cyclase; PLA2, phospholipase A2; PL, phospholipids; PLCβ, phospholipase Cβ; PIP2, phosphatidylinositol 4,5-bisphosphate; cAMP, cyclic AMP; PKC, protein kinase C; TxA2, thromboxane A2; IP3, inositol 1,4,5-trisphosphate; DAG, 1,2-diacylglycerol. The G proteins that are involved are not shown.)