Flashcards in Haemostasis - Platelet Function Deck (22)
What is the main role of primary haemostasis?
Formation of the primary platelet plug
What is the main role of secondary haemostasis?
Stabilisation of the platelet plug
What is the main role of fibrinolysis?
Breakdown of fibrin to localise the clot to the site of injury and remove the clot when healing has occurred.
What are the 3 processes involved in haemostasis? And what is the main factor involved in each?
Primary haemostasis: platelets
Secondary haemostasis (AKA coagulation): thrombin
What is the role of haemostasis?
1. Stop blood loss at site of injury
2. Stop spontaneous blood clotting (i.e. Ensure blood remains liquid)
Outline the steps in primary haemostasis after endothelial injury.
1. Constriction of blood vessel - vasospasm decreases flow rate, initiated by chemical release from platelets and endothelial cells
2. Adhesion - binding of platelets to sub endothelial collagen (GP VI, GP Ia/IIa) and von Willebrand factor receptor (GP Ib/IX/V)
3. Platelet activation - change shape (form pseudopods), release granules (ADP, TXA2, fibrinogen and vWF), express fibrinogen receptor (GP IIb/IIIa)
4. Recruitment of more platelets
5. Aggregation of platelets and formation of plug
Abnormalities in which steps of primary haemostasis can lead to bleeding tendency?
1. Granule release
- normally released from platelets
- deficiency in granules impacts platelet function
- causes bleeding phenotype
2. Expression of fibrinogen receptors
- normally expressed by platelets and allow bridge formation between platelets
- abnormality in fibrinogen receptors results in Glanzmann thrombasthenia
What is ITP and what is the key indicator in the full blood count?
Immune thrombocytopenic Purpura
- indicated by low platelet count (1x10^9/L vs RR 150-450x10^9/L)
What is the initiator of the coagulation cascade?
Binding of tissue factor and circulating factor VIIa
(Tissue factor is sub endothelial and is exposed by vessel injury)
Outline the steps in coagulation.
1. Tissue factor binds to factor VIIa
2. Activates other factors (e.g. Factor X) which results in a small amount of thrombin (Factor IIa)
3. Thrombin activates platelets and other factors (e.g. Factor XII, Factor VIII, Factor V) that are required for its own production (i.e. positive feedback on thrombin production)
4. Large scale production of thrombin
5. Thrombin activates fibrin
5. Fibrin forms bridges between platelets to form a stable clot
Outline the steps in fibrinolysis
1. Tissue plasminogen activator (tPA) activates plasminogen and converts it to plasmin
2. Plasmin enzymatically degrades fibrin, producing fibrin degradation products that are slowly degraded
What prevents platelets from adhering to healthy endothelium?
Prostacyclin and nitric acid production
Which component of the blood is used for coagulation assays?
Plasma (contains clotting factors)
Outline the principles of all coagulation testing
- perform on citrated (Ca2+ chelated/removed) blood
- centrifuge to remove cellular elements
- add activator, platelet substitute (phospholipid), calcium to initiate clot formation
- measure time to clot formation
Define APTT. Which pathway does APTT evaluate?
Activated partial thromboplastin time
- evaluates intrinsic pathway (VIII, IX, XI, XII)
Define PT. Which pathway does it evaluate?
- evaluates extrinsic and common pathway (X, VII, V, II)
Define TT. What does it measure? What are the 2 types of the test?
- measures conversion of fibrinogen to fibrin
- 2 types: functional and immunological
- functional evaluates quantity and quality (commonly used)
- immunological evaluates quantity only
What is the most important screening test for bleeding disorders?
(Triggers, drug use, family history)
If PT and APTT are normal. Does this rule out bleeding disorder?
No, this doesn't rule out the possibility of a bleeding disorder. Clinical history is the best screening test and can tell us more than the lab screening.
What is Virchow's triangle made up of?
-Injury to epithelium
-Alteration to blood glow
Where does deep vein thrombosis usually occur?
In the calf, as blood becomes static in the veins