Haemostasis Flashcards
What is haemostasis?
Process involving stoppage of blood through blood vessels following trauma
What is primary haemostasis?
Formation of unstable platelet plutons at the site of damaged vessel wall
What is secondary haemostasis?
Coagulation, formation of stable fibrin clot
What is coagulation?
Stimulation of blood clotting process whereby blood transitions from a liquid to semi-solid state, forming a coherent mass
What is thrombosis?
Limit the extent of the response to the area to injury to prevent excessive or generalised blood clotting
Thrombosis is localised coagulation
What is fibrinolysis?
Initiating the process to enzymatically breakdown the fibrin in blood clots.
What is the structure of platelets?
Non-nucleated discoid granule containing cells
What cells do platelets derive from?
Megakaryocytic cytoplasmic fragmentation
Myeloid progenitor cells, formed in the bone marrow
What glycoprotein receptor do platelets directly bind onto within the collagen exposed damaged endothelium?
Glycoprotein-1a receptor
What receptor do platelets indirectly bind onto?
Von willebrand factor
What does Von Willebrand factor bind with?
Glycoprotein-1b
What results from platelet adhesion?
Structural changes from sacs to rounded discs with interlacing projections
What term describes the interlocking projections on platelets?
Spicules and filopodia
What is the function of spicules and filopodia?
Encourages platelet-platelet interaction
What proceeds platelet adhesion?
Initiates activation and release of clotting factors from storage granules (alpha dense granules), membrane invaginated to form canalicular system through which granules secrete contents, ADP
What platelet system is formed upon platelet adhesion and activation?
Canicular system
What storage granules release clotting factors?
Alpha and dense granules
What is also released upon platelet activation?
ADP
What is produced during platelet activation?
Thromboxane A2 (prostaglandin)
What is thromboxane A2?
Prostaglandin
What is thromboxane A2 synthesised from?
Arachidonic acid
What is the function of thromboxane A2?
Stimulates platelet aggregation, and the activation of new platelets (positive feedback lipids mediator)
Vasoconstrictor
How does thromboxane A2 cause platelet aggregation?
Binds to thromboxane a2 receptor, finalised by conformational change (ADP induced) in GP2B; gp3A to provide binding sites for fibrinogen.
Which glycoproteins undergo conformational change due to thromboxane A2?
GP2B
GP3A
What is fibrinogen?
Soluble blood protein, essential for linking platelets together to form untstable platelet plug
What is prostacyclin?
Potent vasodilator, suppresses platelet activation, and prevents inappropriate platelet aggregation. Stabilises clot
What is the mechanism of action of aspirin?
Aspirin inhibits the production of thromboxane A2 by irreversibly blocking the action of cycle-oxygenase (COX); thereby reducing platelet aggregation
How long does a single dose of aspirin persist?
7 days,
What is the mechanism of Acton of clopidrogel?
Irreversibly blocks the ADP receptor P2Y12 on platelet cell membrane; thus ADP induced conformation change cannot occur
What is von Willbrand factor?
Multimeric glycoprotein synthesised by endothelial cells and megakaryocytic, mediates the adhesion of platelets binding onto glycoprotein-1b receptor.
What is secondary haemostasis?
Secondary haemostasis is responsible for the formation of a stable clot through coagulation mechanisms. The primary platelet plug is insufficient for larger vessel injury (structurally weak)- Fibrin formation stabilises the platelet plug, adding integrity.
What is the function of thrombin?
Proteolytic enzyme cleaves fibrinogen to an insoluble protein, fibrin; forms fibrin mesh fibre
Where are the majority of clotting factors synthesised in?
Liver
Whereis factor V synthesised?
megakaryocytes
Where is VWF made?
Megakaryocytes + endothelial cells
Which clotting factors are dependent on vitamin K?
Factors II (Prothrombin)
VII (7)
IX (9)
X (10)
Why is vitamin K essential for the four clotting factors?
For their glutamic acid resides to be carboxylated into activation
What is the term for inactive enzyme (proenzyme)?
Zymogen