B6 - basics of haemostasis Flashcards
(37 cards)
○ In the absence of injury
§ Intact endothelium prevents platelet adherence by production of Nitrous oxide and prostacyclin
§ Keeps blood flowing smoothly with laminar flow
Following vascular injury
there is reflex vasospasm of smooth muscle (transient)
§ Expose subendothelial matrix
○ Injury exposes important proteins in subendothelium that activate proteins that activate coagulation
§ VWF
§ Tissue factor
Circulating platelets bind to subendothelial matrix (at the site of vascular injury) through platelet surface receptor
(glycoproteins 1b/IX/V complex) via von-Willebrand factor (VWF)
surface receptor on platelets that binds to sub endothelial matrix
□ Glycoprotein 1B/IX/V complex
® Surface glycoprotein on the platelet allowing it to bind via von Willebrand factor
other interactions contributing to platelet adherence to sub endothelial matrix
GP1a/IIa, GPVI binding to collagen - less important than ib/IX/V complex
Activated platelets
change shape, release the contents of their granules (which contains substances such as ADP, TXA2, fibrinogen, VWF)
□ Leads to further platelet activation at the site through ADP
platelets are activated by
§ Platelets are activated by collagen, VWF, thrombin, ADP
fibrinogen receptor
Express glycoprotein IIb/IIIa in an active form on the platelet surface
Glycoprotein IIb/IIIa receptor
§ Express glycoprotein IIb/IIIa in an active form on the platelet surface (fibrinogen receptor)
□ Glycoprotein IIb/IIIa receptor is always on the platelet surface but only exists in an activated form when the platelet is activated
□ This activated form is the main binding process through which platelets bind fibrinogen
platelet shape change
□ In resting state, they are smooth disk shape
□ Become spikey cells when activated allowing for better cross binding
□ When clot matures they because flat and spread out
purpura
□ Immune thrombocytopaenia purpura
® Normal bone marrow production of platelets
® Platelets are rapidly consumed by antibody mediated mechanisms
® Surface bleeding, mucosal bleeding, bruising
- Clotting cascade (generation of fibrin clot)
○ Tissue factor is exposed in the subendothelial system
○ combines with factor VIIa (circulating factor in the blood) to form a small amount of FVIIa-TF complex
○ FVIIa-TF complex activates other clotting proteins leading to a small amount of thrombin production
○ Through feedback mechanisms large scale production of thrombin takes place on platelet surface
○ Thrombin converts fibrinogen to fibrin which forms the basis of the clot
○ Fibrin mesh at site of injury
initiation of clotting cascade
□ Initiation of clotting occurs when disruption of the endothelium exposes activated factor VII (VIIa) in blood to tissue factor on subendothelial cells (smooth muscle cells and fibroblasts)
□ FVIIa-TF complex activates other clotting proteins (esp. FX to FXa and FIX to FIXa)
□ Small amount of thrombin is formed
propagation of clotting
□ Thrombin (Factor IIa) activates platelets which release further coagulation proteins
□ Thrombin activates coagulation proteins required for it’s own production (feedback)
□ Large scale production of thrombin takes place on platelet surface
□ Thrombin catalyses fibrinogen to fibrin - forming structure of clot
□ FXIII because FXIIIa which allows for cross linking between fibrin stands
○ Clot stabilisation
§ Thrombin cleaves fibrinogen to fibrin
§ Fibrin strands provide the structural integrity to the thrombus
§ Factor XIII allows cross linking of fibrin monomers
§ Fibrinolysis is activated to localise the clot to site of injury and remove clot when healing has occurred
- Fibrinolysis (breakdown of the fibrin clot)
○ The process by which a clot is removed
○ Tissue plasminogen activator (tPA) activates plasminogen and converts it to active plasmin
○ Plasmin enzymatically attacks the fibrin molecule producing fibrin degradation products (FDP’s) that are cleared from the circulation by macrophages
summary of coagulation
○ Platelets bind to subendothelium collagen to initiate primary closure of the vessel wall defect
○ Tissue factor in subendothelium combines with FVII in blood to form the FVIIa-TF complex
○ FVIIa-TF complex activates other clotting proteins leading to thrombin production
○ Large scale production of thrombin takes place on the platelet surface
○ Thrombin converts fibrinogen to fibrin to form cross linked fibrin clot
○ Fibrinolysis is activated to localise the clot to the site of injury
biological amplification system
- Incredibly efficient: 1 mole XIa generates ~107 moles XIIa
- Clotting factors numbered I-XIII
- Binding of FVII to tissue factor (TF) initiates coagulation
§ Activates
□ FXI to XIa
□ FV to Va
□ FVIII to VIIIa
§ Massive but highly focussed burst of thrombin
□ Rapidly converts soluble fibrinogen to insoluble fibrin
□ Fibrin reinforces and stabilises the platelets ‘plug’
contact pathway/intrinsic pathways
plays a lesser role
eg. deficiencies of factor 12 cause no increases tendencies of bleeding
extrinsic/tissue pathway
main way of coagulation cascade activation in vivo
if PT is normal
but be a problem with APTT arm
If APTT is normal
must be a problem with factor 7
citrated blood
- citrate decalcifies the blood
- calcium is a cofactor for coagulation cascade to the blood stays liquid in the tube
- Centrifuge blood to take out platelets and cellular components
- Add activator and platelet substitute
- Add calcium
- Measure time to clot formation
