Haematology 3 - Coagulation Flashcards
(50 cards)
Recall 4 endogenous anti-coagulants
Anti-thrombin
TFPI
Protein C
Protein S
Recall the 2 possible mechanisms of platelet activation
- vWF binds Gp1b -> binds and activates platelets
- Endothelial Gp1a binds directly to platelet and activates
What role does the vascular endothelium play in coagulation?
Endothelial damage → pro-coag exposure → platelet aggregation
Recalll 3 procoagulant factors and 1 anticoagulant factor that are synthesised in vascular endothelium
PGI2
vWF
Plasminogen activators
Thrombomodulin
What is the lifespan of platelets and what is the clinical significance of this?
10 days (anti-platelet drugs halt activity for 10 days)
if on aspirin and need surgery → stop 7-10 days before
What is platelet production controlled by?
thrombopoietic factors (e.g. thrombopoietin, IL-6, IL-12)
can be given therapeutically to stimulate plt production
Via which receptors to platelets adhere to each other, and what is needed for this to happen?
adhesion direct (GlpIa) or indirect (vWF/GlpIb)
→ release ADP and thromboxane → platelet aggregation via GlpIIb/IIIa
Recall one inducer and one inhibitor of platelet aggregation, and the enzyme required for the synthesis of both
Thromboxane A2 increases aggregation
PGI2 inhibits platelet aggregation
COX enzyme
How do NSAIDs and aspirin affect coagulation?
Aspirin irreversibly inhibits COX enzyme which is necessary for thromboxane A2 production
NSAIDs reversibly block COX
What is the rate-limiting step in fibrin formation?
Factor Xa
MOST IMPORTANT = generation of THROMBIN → fibrinogen to FIBRIN which is the final step in the coagulation cascade
What are PT and APTT indicators of?
PT = INR = extrinsic pathway
APTT = intrinsic pathway
Summarise the steps in coagulation
1) Initiation phase
endothelial damage → TF + F7a activation → F9+F10 activation
F10a binds F5a on cell surface
2) Amplification
10a/5a complex: small amounts prothrombin → thrombin
thrombin: activates F8/5/11 and platelets locally
- F11a: F9 → F9a
- activated plt: bind 5a/8a and 9a
3) Propagation
F8a/F9a complex actiates F10 on surface of activated platelets
F10a + F5a: prothrombin → thrombin (thrombin burst) → stable fibrin clot
Which clotting factors are vitamin K dependent and where are they made?
2, 7, 9, 10 -
prod in liver
(also Protein C, S and Z)
How does vitamin K activate clotting factors?
biological activation = vitamin K is co-enzyme for gamma-carboxylation of clotting factors
Recall 3 causes of vitamin K deficiency
- Bacteria help produce vitamin K → antibiotics can harm gut flora → ↓ vitamin K absorption
- Vitamin K is fat soluble so need bile to absorb vitamin K (i.e. bile duct obstruction → deficiency)
- Most common cause of vitamin K deficiency = WARFARIN
Recall the factors that promote fibrinolysis
Tissue plasminogen activator (tPA) + urokinase (plasminogen → plasmin)
Factor IXa, Xa, TPA and urokinase all implicated
red = inhibitory, blue = stimulatory
What are tPA and urokinase inhibited by ?
plasminogen activator inhibitor 1 & 2
What is the role of plasmin?
Breaks down fibrin in fibriolysis
What is plasmin in inhibited by?
Alpha-2 antiplasmin
Alpha-2 macroglobulin
What is the enzyme that inhibits fibrin breakdown?
Thrombin-activatable fibrinolysis inhibitor (TAFI)
How does antithrombin work?
bind thrombin 1:1 → excreted in urine
ATIII most active
AT deficiency = MOST THROMBOGENIC
What is the mechanism of action of heparin?
Heparin = AT-III potentiator (monitor levels with F Xa assay)
What is the role of proteins C and S?
To stop thrombin, F5a and F8a need to be inactivated
Thrombin activates thrombomodulin -> opens receptor -> TM binds Protein C (EPCR)
→ activated protein C (APC)
APC + protein S → fully activate protein C ⇒ inactivates F5a and F8a
What are the roles of tissue factor and TFPI
Tissue factor activates factor Xa
TFPI neutralises tissue factor
