Haematology 3: Haemostasis And Bleeding Disorders Flashcards
List 4 Pro-coagulant factors in the body?
Platelets
vWF
Endothelium
Coagulation cascade
List 4 Anti-coagulant factors in the body ?
AT (antithrombin)
Protein S + Protein C
TFPI (Tissue factor pathway inhibitor)
Fibrinolysis
List 2 thrombopoietic factors ?
Thrombopoietin
IL-6
IL-12
Which Surface glycoprotein do platelets use to bind to vWF ?
GpIb
Which glycoprotein do platelets use to bind directly to collagen ?
GpIa
Which glycoproteins do platelets use to bind to other platelets when aggregating ?
GpIIb/IIIa
Which 2 mediators do platelets release when they bind to subendothelial structures (vWF or collagen) to cause platelet aggregation ?
ADP
Thromboxane A2
How does Aspirin inhibit platelet aggregation?
aspiring irreversibly Inhibits Cyclo-oxygenase (COX)
This prevents Arachidonic acid being converted to endoperoxides
This prevents formation of thromboxane A2
Less Thromboxane A2 means less platelet aggregation
List 2 drug targets for inhibiting platelet aggregation ?
Thromboxane A2 production - Aspirin
ADP receptors - Clopidogrel
Which pathway is more important for coagulation in the human body ?
A) Intrinsic pathway
B) Extrinsic pathway
C) Contact activation pathway
B) extrinsic pathway
Describe the sequence of events in the Initiation phase of the Clotting cascade ?
1) Damage to endothelium causes TF to be exposed
2) Factor VII binds to TF and becomes activated to FVIIa
3) FVIIa/TF complex activate FIX and FX to FIXa and FXa
4) FXa binds to FVa
Describe the sequence of events in the activation phase of the clotting cascade ?
1) FXa/FVa complex converts prothrombin to thrombin
2) Thrombin activates FVIII, FXI and recruits more FVa
3) FXIa activates FIX to FIXa
4) Activated platelet binds FVa, FVIIIa and FIXa
Describe the sequence of events in the propagation phase of the clotting cascade ?
1) FVIIIa/ FIXa complex on platelets activates FXa on the surface of the platelet.
2) FXa and FVa cause a “thrombin burst” where loads of Prothrombin is converted to Thrombin
3) Thrombin converts fibrinogen to fibrin
4) Fibrin is cross linked to form a stable fibrin clot
Which 4 clotting factors are vitamin K dependent ?
10
9
7
2
Think 1972
What is the role of tPA (tissue plasminogen activator) ?
- Converts plasminogen to plasmin
- Plasmin cleaves The fibrin clot
tPA is produced by the endothelium
Which of these molecules does not promote Plasminogen conversion to Plasmin ?
A) tPA B) Urokinase C) FXIIa D) FXIa E) PAI 1
E) PAI1
Plasminogen activator inhibitor inhibits Plasminogen conversion to Plasmin by inhibiting Urokinase and tPA
What does TAFI do ?
TAFI (thrombin Activated Fibrinolysis inhibitor) is a Thrombin dependent inhibitor of Fibrin breakdown
Deficiency of which component is the most Thrombogenic ?
A) TAFI B) FVIIIa C) AT3 D) vWF E) Protein S
C) AT3
Deficiency of Antithrombin (AT) is very rare but is the most thrombogenic
What is the role of Protein C and protein S ?
Inhibit FVIIIa and FVa
What is the role of Thrombomodulin ?
Thrombomodulin is an endothelial receptor for Protein C
It first needs to be activated by Thrombin.
EPCR is another receptor which helps Thrombomodulin bind to protein C
When Thrombomodulin binds to Thrombin and Protein C the complex is called APC (activated protein C)
What is the role of APC (activated protein C) ?
APC inactivates FVa and FVIIIa
Requires protein S as cofactor
What is different in the interaction between APC and FVa in people with Factor V Leiden ?
People with Factor V Leiden have APC resistance.
This means activated factor V is not inactivated by APC.
What is the physiological role of TFPI as an anticoagulant ?
TFPI neutralises the TF/FVIIa complex.
TFPI is produced as a result of TF/FVIIa complex formation in order to stop activation by the extrinsic pathway. (TF/FVIIa is only required for a very short time to activate FX and FIX)
What disease is associated with large platelets ?
grey platelet syndrome
