Haemostasis Flashcards
What is Haemostasis?
It is the prevention of blood loss:
- Vascular constriction
- Formation of a platelet plug
- Formation of a blood clot
- Growth of fibrous tissue into the blood clot to close the hole permanently
Vascular Constriction
How does vascular constriction occur? • Trauma causes the smooth muscle in the wall of the blood vessel contract –reduces blood flow • Caused by – by nervous reflexes – pain nerve impulses. – Local myogenic spasm – Local autocoid (hormone-like) factors
Formation of the platelet plug
Platelets swell
• Assume irregular forms with numerous irradiating pseudopods
• Contractile proteins contract forcefully
• Cause release of granules (contain multiple active factors).
• Become sticky and adhere to collagen in tissues (adhesion)
• Also adheres to a protein called Von Willebrand‘s factor (leaks into the traumatized tissue from the plasma) – prevents platelets from being pulled off collagen by blood flow
Secrete large quantities of ADP
• Forms thromboxane A2 (helps maintain vasoconstriction).
• Thromboxane A2 and ADP activate nearby platelets - cause them to adhere to the original platelets.(activation)
• This activation continues to attract more and more additional platelets, forming the platelet plug. (aggregation)
• This is initially a loose plug, but it is sufficient to block blood loss if the opening is small.
– Important for closing minute ruptures that occur several thousand times daily.
• Fibrin threads are needed that attach tightly to the platelets to form an unyielding plug.
Formation of blood clots
Clotting takes place in 3 steps:
1. Rupture of the vessel or damage to the blood itself
• Causes cascade of chemical reactions involving >12
blood coagulation (clotting) factors
• Forms prothrombin activator (rate-limiting factor)
2. Prothrombin activator catalyzes the conversion
prothrombin into thrombin (requires Ca2+ions)
• Prothrombin is attached to platelets (via prothrombin
receptors) that are bound to damaged tissue.
3. Thrombin converts fibrinogen into fibrin fibers
• These enmesh platelets, blood cells, and plasma to
form the clot.
The role players are: Clotting factors
Factors I - Fibrinogen Factor II - Prothrombin Factor III - Tissue factor /Tissue thromboplastin Factor IV - Calcium Factor V - Proaccelerin Factor VII Factor VIII Factor IX Factor X Factor XI Factor XII Factor XIII
What is Prothrombin?
=Factor II
Unstable protein that can split into smaller compounds,
one of which is thrombin.
• Continually formed in the liver
• Continually being used for blood clotting
• Vitamin K required by the liver for normal formation of
prothrombin (and other clotting factors).
What is Thrombin?
Protein enzyme with weak proteolytic capabilities
• Acts on fibrinogen to remove 4 low-molecular
weight peptides from each molecule.
• Forms one molecule of fibrin monomer
• This monomer can polymerize with other fibrin monomers to form long fibrin fibers. This constitutes the reticulum of the blood clot
What is fibrinogen?
Occurs in the plasma.
• Formed in the liver
• Because it is large does not usually leak from the blood vessels into interstitial fluids. Therefore
Interstitial fluids normally do not coagulate.
• When permeability increases due to pathogens,
fibrinogen leaks into the tissue fluids in sufficient quantities to allow clotting.
Formation of prothrombin activator.
What stimulates the formation of prothrombin activator?
• Trauma to the vascular wall and adjacent tissues
• Trauma to the blood
• Contact of the blood with damaged endothelial cells or collagen
(or other tissue elements) outside the blood vessel.
How is it formed?
• Extrinsic pathway (in the vascular and tissue)
• Intrinsic pathway (in the blood)
• Both involve blood-clotting factors (denoted by Roman numerals)
that are activated (denoted by an “a”) eg Factor VIIIa
• Causes the successive cascading reactions of the clotting process
Extrinsic pathway
Activator here is the Tissue factor
- Factor VII comes together with tissue factor and produces an activated form of factor VII CALLED VIIa
- [VIIa + tissue factor + calcium+ phospholipids ] this complex joins with factor X and Factor X become Xa [activated]
Intrinsic pathway
IXa is in the VIII complex [VIII, IXa, calcium, phospholipids] this complex joins with X –>Xa
Activator is the exposure of blood to collagen, glass, or other things.
- Factor XII activated by that exposure above mentioned and becomes XIIa
- XIIa comes together with XI and that becomes XIa
- XIa comes together with IX and that becomes IXa
- The IXa joins factor X and that becomes Xa
Common pathway
This is where the Extrinsic and Intrinsic pathways meet
- X becomes Xa from joining with products from Extrinsic and intrinsic pathways.
- V complex [V, Xa, calcium, phospholipids] this complex joins with Prothrombin and converts it to Thrombin.
- Thrombin converts Fibrinogen to Fibrin —–XII—> Fibrin Polymer.
Dissolution of the blood clot
What happens to the blood clot after the bleeding has stopped?
- Become invaded by fibroblasts and form connective tissue throughout the clot.
• Usually for clots that form in a
small hole. Promoted by growth factor secreted by platelets. Complete organization into fibrous tissue within 1-2 weeks. - Dissolve.
When excess blood has leaked into the tissues and when tissue clots have occurred where they are not needed. Substances within the clot itself (usual plasmin) become activated and dissolve the clot
Why doesn’t blood coagulate all
the time?
• >50 substances affect blood coagulation
• Some promote coagulation = procoagulants
• Some Inhibit coagulation = anticoagulants
• Whether blood will coagulate depends on the balance
between the two groups of substances = the haemostatic balance
What happens normally?
• Anticoagulants predominate in the bloodstream
• Blood does not coagulate
What happens when a vessel is ruptured?
• Procoagulants become activated and override the
anticoagulants, allowing the clot to develop
Intravascular anticoagulants -How is clotting prevented?
How is clotting prevented?
• Smoothness of the endothelial cell surface
• Prevents contact activation of the intrinsic pathway
• Layer if glycocalyx
• repels clotting factors and platelet
Thrombomodulin
•Binds thrombin (i.e. removes thrombin)
Thrombomodulin-thrombin complex activates
protein C, which inactivates activated Factors V and
VIII (anticoagulant)
