Haemostasis Flashcards
General steps of haemostasis
1) Trauma/breach of vascular barrier triggers reflex vascular spasm -> slow down blood flow towards puncture site -> decreased blood loss
2) Primary haemostasis -> formation of platelet plug
3) Secondary haemostasis -> formation of blood clot
4) Clot dissolution
What is thrombopoiesis?
Formation of platelets
What does thrombopoietin (TPO) stimulate?
Thrombopoiesis
Which organs produce TPO?
Liver and kidney
What is a megakaryocyte?
Precursor for platelets
- can’t enter circulation directly -> turn into fragments first
What kind of feedback loop does thrombopoiesis utilise?
Neg feedback loop
How is TPO removed?
Via circulating platelets
What is the lifespan of platelets?
~ 10 days
Where are old platelets removed?
Spleen
How is a platelet plug formed?
1) Platelet adhesion to exposed collagen and subsequent activation (change morphology into ‘spiky’ form)
2) Release of granules containing platelet agonists -> attract more platelet toward puncture site -> encourage further aggregation
3) Platelet aggregates to form plug and release more platelet attracting substances
4) Intact endothelial cells releases NO and prostacyclins that inhibits unintentional platelet activation/aggregation
How does body inhibit uncontrolled platelet formation?
Intact endothelial cells releases NO and prostacyclins that inhibits unintentional platelet activation/aggregation
What is Von Willebrand’s factor (vWF)?
Plasma protein produced by platelets that mediate platelet adhesion by binding platelets to exposed collagen
How does vWF bind platelets to exposed collagen?
Via glycoprotein receptor found on surface of aggregated platelets
What does adhesion do to platelets?
Activates platelets -> morphological change; spikes -> greater surface area for attachment of platelet
How does aggregation of platelets occur?
Adhesion triggers release of granules containing platelet agonists -> aggregation
Eg of platelet agonists
ADP, thromboxane A2 (Tbx A2)
What does ADP do?
Attracts and activates more platelets
What does Tbx A2 do?
Promote aggregation and further vasoconstriction at puncture site
What does fibrinogen do?
Links platelets through glycoprotein receptors
Characteristic of fibrinogen links
Weak, temporary -> need further reinforcement via secondary haemostasis
Describe the process of secondary haemostasis
Formation of strong and insoluble fibrin mesh -> trap all the blood cells and clotting factors that try to escape from damaged vessel
What does thrombin do?
It cleaves and activate fibrinogen as well as factor 13 -> factor 13a
What is fibrinogen?
Insoluble protein where fibrin mesh originates from
What does fibrinogen do?
Crosslinks platelets tgt
How is a fibrin strand formed?
Fibrinogen (soluble) cleaves and activate into fibrin monomer (insoluble) which polymerise into fibrin strand
What is a fibrin mesh?
Many fibrin strands crosslinked tgt
What crosslinks fibrin strands?
Factor 13a (fibrin stabilising factor)
What is prothrombin?
The inactivated form of thrombin that is present in circulation
How is prothrombin activated into thrombin?
Factor 10 -> factor 10a which cleaves and activates prothrombin to form thrombin in the presence of Ca2+ and factor 5a
What are the diff pathways of the coagulation cascade?
Extrinsic
Intrinsic
Common pathway
How many common coagulation factors are there?
12
Which coagulation factors are involved in the extrinsic pathway (exclude the common pathway)?
Factor 7
What are the steps to the common pathway?
Factor 10 -> factor 10a which cleaves and activate prothrombin to thrombin in the presence of Ca2+ and factor 5a
Thrombin cleave and activate factor 13 -> factor 13a
Thrombin cleave and activate fibrinogen -> fibrin —> fibrin strand -> fibrin mesh (crosslinked by factor 13a)
What are the steps to the extrinsic pathway (exclude common)?
Damaged tissue releases tissue factor/thromboplastin -> bind to and activate factor 7 to form 7a -> cleave and activate factor 10 in the presence of Ca2+ to form factor 10a -> common pathway
Why is it called the extrinsic pathway?
Tissue factor comes from external sources
What are the steps to the intrinsic pathway?
Exposure to collagen fibres/foreign surface cause factor 12 to undergo conformational change in the presence of platelet phospholipids -> factor 12 activated to factor 12a
Factor 12a cleave and activate factor 11 -> factor 11a
Factor 11a cleaves and activate factor 9 -> factor 9a in the presence of Ca2+
Factor 9a cleaves and activates factor 10 -> factor 10a in the presence of Ca2+ and factor 8a -> common pathway
Why is it called the intrinsic pathway?
Factor 12 initiates the pathway and is a circulating plasma protein (endogenous part of circulatory sys)
Why is haemostatic dressing encouraged?
It’s a foreign surface -> initiate intrinsic pathway
What happens when Ca2+ is absent and it’s application?
Clotting pathway is impaired as many of the pathways req Ca2+
Application: prevent blood in test tube from clotting by adding agent to remove Ca2+
Which factors are not plasma proteins?
Factor 3 and Ca2+
Why does liver damage cause bleeding issues?
Most of the coagulation factors (except thromboplastin and Ca2+) are produced by the liver
Liver damage -> production of clotting factors impaired -> bleeding
Which factors req Vit K for production?
Factors 2, 7, 9 and 10