Clinical Haemostasis Flashcards
(42 cards)
What is haemostasis?
Process of minimising blood loss during injury, blood clotting.
5 systems keep blood in liquid state:
Vascular
Platelets
Coagulation Cascade
Inhibitors of coagulation
Fibrinolytic
Vascular System in Haemostasis
Upon damage, lumen of vessel narrows minimising flow of blood through, decreasing blood lost, bacteria cannot get in, blood pressure drops so platelets can anchor.
Vasoconstriction.
Adrenaline, ADP and thromboxanes regulate, when released by platelets (also serotonin)
Endothelial cells source of pro and anti-thrombotic compounds.
Anti-coagulant aspect of endothelial cells
Glycated muco polysaccharideshave heparin sulphate on surface, slows formation of blood clots.
Keep pro aspect of of coagulation in inactive form.
Pro-thormbotic aspect of endothelial cells
Piercing of tunica media releases pro thrombotic factors it contains, collagen, tissue factor, activate coagulation cascade.
Blood Platelets
-Precursor is mega karyocyte which sheds platelets that do not have a nucleus or some organelles.
-Release alpha (200 per/cell) and dense granules (10 per/cell)
[peptides, signal molecules that encourage formation of blood clots]
[3rd granule is lysosome which maintains cell environment]
-Canalicular System releases granules
What do platelets release?
Alpha and dense granules.
-ADP (mitochondria), adrenaline, serotonin, factor 5 and Von Willerbrand’s factor
Function of platelets?
-platelet plug (transiently attached)
-temporary physical barrier to prevent blood loss (primary homeostasis)
4 Phases of primary homeostasis, formation of platelet plug?
1) Platelet adhesion (to site of damage)
2) Platelet activation
3) Release of platelet granules
4) Platelet adhesion
(veins and arteriole’s high pressure can wash plugs away)
How are platelets adhesion activated?
Upon contact with Collagen, Charged surface, Bacterial endotoxin (exposed in damaged vessel)
Von Willebrand’s Factor Function?
Aids platelet adhesion.
-Large multimeric glycoprotein
produced by platelets and
endothelium.
-Binds to GPIb receptor on platelets
encouraging adhesion.
Platelet Shape Change
-Once bound to a substrate platelets become activated and change their morphology.
-Discoid shape to ameboid.
-Circular shape would leave gaps, ameboid has finger like projections maximising surface area.
-Here granules start migrating to canalicular system
Release of platelet granules?
- Ca2+ mediated fusion of the granules with the canalicular system. [ Ca2+ stored in mitochondria, also released to interstitial fluid for haemostasis]
-Promotes vasoconstriction
-Promoting platelet adhesion (Amplification of adhesion events)
Platelet aggregation?
-Activation of platelets results in platelet GPIIb receptors binding fibrinogen. This results in formation of inter-platelet bridge.
-ADP released from damaged cells and granules allows for self-propagation of platelet aggregation
-End point is primary haemostatic plug
Secondary Haemostasis
-For bigger wounds
-Proper blood coagulation beginning on top of platelet plug.
-Plasma proteins convert soluble fibrinogen to insoluble fibrin (inactive enzymes zymogens and cofactors (proteolytic)
-fibrinogen produced in liver (acute phase reactant)
(most plasma proteins are produced in the liver and that is why liver disease is associated with bleeding)
Coagulation Factors
Named now 1 to 13 roman numerals.
-4 is calcium
-3 is tissue factor
-1 is substate (fibrinogen)
Many are serine proteases (horse shoe crab contamination test)
-Factor 13, fibrin stabilising factor is transglutaminase, links peptides together,
Vitamin K
-Fat soluble requires lipases for absorption from pancreas, essential to haemostasis.
-breaks down clots too
-Uses carboxylation to activate several pro and anti coagulants (2,7,9,10)
-Once activated factors bind Ca2+
V.K carboxylase epoxidase uses V.K as cofactor for carboxylation.
Warfarin (anticoagulant)
-treats thrombo-embolic disease.
-inhibits Vitamin K carboxylase epoxidase
-rat poison
(dosing closely monitored genetic variation in enzyme metabolism, too high, spontaneous haemorrhaging)
International normalized ration 2-3 best above 3 emergency.
Intrinsic pathway of coagulation cascade
Surface contact (initiation) (charged environment)
F12- F12a
F11-F11a
F9-F9a (activates F10)
(a’s are active enzyme start as zymogen)
Extrinsic Pathway of coagulation cascade
Tissue damage (initiation)
Tissue factor (TF) and F7 complex. (activates F10)
Common Pathway of coagulation cascade
F10-F10a
Prothrombin to thrombin converts
F13-F13a and
Fibrinogen to fibrin.
Stable cut
Testing Intrinsic and Extrinsic Pathway for Coagulation?
Intrinsic=activated partial thromboplastin time. (kaolin, charged silicat activation)
Extrinsic=prothrombin time (add tissue factor)
Haemophilia A
- X linked recessive disorder (1/5000 males)
-F8 deficiency (cofactor for F9)
-intrinsic tenase complex formed with F9 activates F10.
Haemophilia B
1/30000 males, 15% of all cases.
- B caused by a deficiency in F9.
Female haemophilia
Very rare,
-Turner’s Syndrome
-Homozygous for F8 Deficiency
-Inappropriate lyonization
