7 - Haemostasis Basics Flashcards
5 main components of haemostasis
Platelets Von Willebrand Factor Tissue Factor Clotting Proteins Anticoagulant proteins
Primary haemostasis
Platelets and vasoconstriction form platelet plug
Thrombocytopenia
Below 150x109 per litre
Thrombocytosis
Over 450x109 per litre
What are platelets released from
Megakaryocyte (can release 1000+ platelets)
What is the function of granules
Secrete proteins needed for a plug
4 steps of primary haemostasis
Vessel Injury
Platelet release reaction
Platelet aggregation
Vasoconstriction
What is the role of Von Willebrand Factor
Assists the platelets to attach to an injured site by binding to collagen and each other
What is released in the platelet release reaction and what is their function
Adenosine Phosphate - causes platelets to aggregate
Serotonin - Vasoconstriction
Thromboxin A2 - Vasoconstriction and platelet aggregation
Extrinsic pathway
When blood vessels are injured
1) TF reacts with F7 -> F7a
2) 7a converts F10 -> 10a
Intrinsic pathway
When clots form without tissue injury
1) F12 -> 12a
2) 12a activates 11 -> 11a
3) 11a activates 9 -> 9a
4) 9a and factor 8 convert 10 to 10a
Common Pathway
1) 10a turns prothrombin to thrombin
2) thrombin turns fibrinogen to fibrin
What is the amplification stage
The small amount of thrombin produced from the extrinsic pathway activates factors 5,7,8,11 and 13
What is the role of antithrombin
Thrombin produces antithombin which converts plasminogen to plasmin (destroys cross links in fibrin formed by factor 13) and stops X to Xa
Test for the extrinsic pathway
Prothrombin Time
Test for intrinsic pathway
Activated Partial Prothrombin Time
What are the normal values for bleeding time
3-10minutes
What is the normal range for INR
0.8-1.2
Haemophillia A
Deficiency of factor 8
Haemophilia B
Deficiency of factor 9
What holds plasminogen in it’s inactive form
alpha-2 antiplasmin
D-dimer
Product of fibrin breakdown
Low levels indicate no thrombosis
What structures to platelets contain to stop bleeding
Proteins on surface allow them to stick
Granules secrete proteins
Contain proteins to allow them to change shape
How do platelets change their shape when activated
First like a plate
activated by contact with materials such as collagen (due to break in blood vessel wall)
Extend long filaments which interlock and erythrocytes can be trapped
How long is platelet lifespan
8-14 days
removed by reticuloendothelial system
Structure of platelet
Lipid bilayer + microtubular system
9 glycoproteins
Cell membrane receptors - GpIIb/IIIa, gbIb
What does a dense granule contain
ADP and calcium
What do alpha granules contain
P selectin PDGF Factor V VWF Fibrinogen
How is vWF bound to platelets and what does it do
Vessel injury
Platelets adhere to collagen + vWF via gb1b
gPIIb/IIIa exposed via vwf binding forms a second binding site for vwf
Fibrinogen bound to promote platelet aggregation
GpIb deficiency
Bernard Soulier Syndrome
GpIIb/IIIa deficiency
Glanzmann’s
Treatment for vWF disease
DDAVP
Tranexamic acid
vWF containing concentrate
Types of VWF disease
Type 1 - mild/moderate deficiency
Type 2 - present but defective
Type 3 - total absence
Where is tissue factor and what is its function
Present on subendothelial tissue
Expressed by cells which are not normally exposed to flowing blood
Physical injury exposes TF to flowing blood
Initiates clotting via factor 7
Role of vWF
vWF binds to GpIb, subsequent activation via G-protein –> shape change –> disc to sphere –> pseudopods–> complex of GpIb, IIbIIIa, vWF, fibrinogen
vWF agonists
collagen ADP thrombin adrenaline TXA2
What does factor 10 need to turn prothrombin to thrombin
calcium
factor 5a
What is the INR
Practical form of prothrombin time
What INR do you aim for in patients taking warfarin
2-3
Function of tissue plasminogen activator
Released from normal endothelial cells
Catalyses plasminogen to plasmin
When is TPA released
when the wound has healed
no longer need a clot
What other molecules affect plasmin
- urokinase plasminogen activator, kallikrein, and factor XIIa
What is the function of antithrombin
Inhibits thrombin, 9,10, 11
Member of serine protease inhibitors
Binds to heparan sulfate on vascular endothelium
Function of vitamin C
Activated by thrombin
Serine protease
Inactivates 5 and 8
Function vitamin S
cofactor for protein C (apc)
What are vitamin C and S dependent on
Vitamin K
