Haemostasis Flashcards
what is haemostasis and what is it for?
βProtective process evolved in order to maintain a stable physiology
βcurtail blood loss
βrestore vascular integrity
βultimately preserve life
what does DIC stand for?
βdisseminated intravascular coagulation
The Horseshoe Crab
βLimulus Polyphemus
β βA primitive coagulation pathway can be initiated by endotoxinβ
what are the Four Key Components of haemostasis?
βEndothelium
βCoagulation
βPlatelets
βFibrinolysis
what does a blood clot consist of?
βFibrin mesh
βPlatelets
βRed blood cells
what are the simplified steps of haemostasis?
βTissue injury βVasoconstriction βPlatelet activation βHaemostatic plug βCoagulation βStable clot formation βClot dissolution
Primary haemostasis:
βVasoconstriction (immediate)
βPlatelet adhesion (within seconds)
βPlatelet aggregation and contraction (within minutes)
Secondary haemostasis:
βActivation of coagulation factors (within seconds) βFormation of fibrin (within minutes)
Fibrinolysis:
βActivation of fibrinolysis (within minutes)
βLysis of the plug (within hours)
what is the purpose of the vessel wall?
βNormal Endothelium:
β inhibits coagulation
β prevents platelet aggregation
Provides a barrier to reactive elements in the subendothelium
βcollagen fibronectin
β tissue factor
Haemostasis at rest
triggers and cofactors separated
what are the functions of Von Willebrand Factors?
βForms a bridge between damaged vessel wall (collagen) and platelets (primary haemostasis)
βStabilises and protects Factor VIII from rapid clearance
Loss of VWF function
βresults in a bleeding disorder
VWF synthesis and storage
Synthesis
βEndothelial cells contain Weibel Palade bodies
βMegakaryocytes
βPlatelet a granules
βPlasma VWF entirely derived from endothelial cells
Distribution of VWF
βConstitutive path (95%)
βRegulated path (5%)
βWeibel-Palade bodies (storage granules of endothelial cells)
Platelet activation
βResting
βPlatelet Activation
βAdhesion + spreading (increase SA)
what happens when a vessel wall is damaged?
βvarious signalling molecules are expressed / exposed, βincluding tissue factor and collagen
describe Initiation of coagulation
βThe TF leads to the production of a small local amount of thrombin, which is the initiation step of the coagulation process
describe adhesion
The exposed signalling molecules attract circulating platelets, which attach themselves to the exposed sub-endothelial tissue
describe secretion
These platelets become activated
β principally through the presence of the thrombin
β release further attractant chemicals
βwhich attract more platelets
describe aggregation
βThese new platelets bind to the adhered platelets and themselves become activated
describe contraction
βThrough the conformational changes inherent in activation
βthe loose platelet plug contracts to form a dense, adherent plug
what do activated platelets present?
βnegatively-charged phospholipid membrane at the site of the injury
βon which the process of coagulation (secondary haemostasis) can occur, if needed
what does the fibrin mesh do?
βFibrin mesh binds and stabilises platelet plug and other cells