Hemostsis & ThrombosisDr Alok TripathiDepartment of Biotechnology

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

Components of hemostasis

Hemostasis is 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

CoagulationInflammation

Wound healing

HEMOSTASIS

Fibrinolysis

Three phases of hemostasis•Primary hemostasis

▫formation of a platelet ‘plug’ •Secondary hemostasis

▫consolidation of the platelet plug by fibrin •Fibrinolysis

▫cleanup

Primary hemostasisactivation in response to stimuli adherence to the margins of the lesion release of granule contents aggregation into a primary platelet plug

The platelet

GpIb

GpIIb/IIIaDense granule

Alpha granule

Cell membrane

Coagulation proteins

Fig. 1. Wound healing 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.]

Normal Hemostasis: 1General Sequence of Events are:

three main mechanisms underline the haemostatic process

Normal Hemostasis:2 General Sequence of Events are:

Endothelium

Modulate several aspect of anti-cougulating properties

It may activated by infectious agents, hemodynamic factors plasma mediators &

CK

Anti-platelet ,Anti-couagulent & fibrinolytic

Exerts pro-couagulent functions

Antithrambic Properties•An intact 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

Vasoconstriction

Figure 51–8. Diagrammatic representation 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 considereda 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.)