Haemostasis 2 Flashcards
What is another name for procoagulant?
Thrombogenic
What is another name for anticoagulant?
Antithrombogenic
Which factors are referred to by their common name?
Factors 1 to 4
Fibrinogen
Prothrombin
Tissue factor
Calcium
Which factor no longer exists
Factor 6 -> it was named incorrectly
Which factors have not yet been assigned Roman numerals?
(2)
Prekallikrein
Kininogen
Which factors have more than one factor
Factors V and VIII are also referred to as the labile factors
This is because their coagulant activity is not durable in stored blood
What are the vitamin K dependent factors
II
VII
IX
X
Why are factors II, VII. IX and X referred to as vitamin K Dependent Factor?
(2)
During their biosynthesis in the liver, a series of post translational enzymatic reaction include a step that required vitamin K to function as a cofactor to a carboxylase enzyme
Vitamin K serves as an essential cofactor for a carboxylase that catalyses carboxylation of glutamic acid (Gla) residues on vitamin K-dependent proteins
What is haemophilia C?
Complete lack of factor XI
What are the symptoms of haemophilia C
exhibit mild haemorrhagic disorder
What happens if a patient has trace quantities of factor XI?
They can have withstand major trauma without unusual bleeding
What is Haemophilia A
Complete lack of factor 8
What is Haemophilia B
Complete lack of factor 9
What is the main pitfall of the the coagulation cascade theory of the intrinsic and extrinsic pathways?
(4)
Doesn’t explain why Haemophilia A or B results in an inability to clot blood
Loss of factor 8 or 9 are from the intrinsic pathway
Therefore clotting should form from the extrinsic pathway
This means the theory may only provide a reasonable model of in vitro coagulation test e.g. aPTT and PT
Current evidence proposes what theory
(2)
The intrinsic pathways is not a parallel pathway to the extrinsic
Instead the intrinsic pathway augments thrombin generated primarily by the extrinsic pathway
What factors are involved in the extrinsic pathway
(4)
Tissue factor
VII
X
Calcium
Where is tissue factor produced
Released by damaged endothelial cells
What is the role of tissue factor?
(2)
It is a co-factor with factor VII
It helps convert X to Xa
What factors are involved in the intrinsic pathway?
(9)
XII
XI
IX
VIII
X
Prekallikrein (PK)
Kininogens (HK)
Calcium
Platelet phospholipids
How is PK converted to kallikrein
Activated platelets present a negatively charged surface which activates PK to kallikrein
What does kallikrein do?
This protease activates Factors XII to XIIa
What does factor XIIa do?
Converts XI to XIa which converts IX to IXa which converts X to Xa = cascade
This needs Ca++ as a co-factor
What is calcium needed for?
It mediates the binding of the coagulation factors to the negatively-charged phospholipids surfaces expressed by platelets via the negatively charged residues on Factor Xa and Factor IXa
It is also required at other points in the coagulation cascade
Where are negatively-charged phospholipids found
Found on the surface of activate platelets
Who proposed the cell based model of coagulation
D. Monroe
M. Hoffman
What is notable about the cell based model of coagulation?
The cascade is a biochemical model
Not a true reflection of what happens in the body
What are the three differences between the cascade and cell based model of coagulation?
Give three characteristics of the cascade
Cascade
- extrinsic and intrinsic pathways work independently, meet at common end-point
- Both can generate large amount of thrombin to form clot
- Coag factors control the rate of coagulation, cells are only phospho-lipid surface
What are the differences between the coagulation cascade and the cell based model?
(Give five characteristics of the cell based model)
Cell Based
- Extrinsic pathway initiates the process
- Generates small amount of the Thrombin Spark
- Followed by Intrinsic Pathway, works on platelets to produce the Thrombin Burst
- No role of factor XII
- Cells (platelets and endothelium) control the coagulation
What are the five steps to the cell based model of coagulation?
Initiation (TF Cell)
Amplification (platelet)
Propagation (active platelet)
Stabilisation of clot
Inhibition of further coagulation
How is the cell based model initiated?
(5)
It occurs by expression of Tissue Factor
Tissue binds factor VIIa to activate factor IX and factor X
This activation of factor IX by TF-VIIa complex serves as the bridge between classical extrinsic and intrinsic pathways.
Factor Xa then binds to factor II to form thrombin (factor IIa)
Thrombin generation through the reaction is not robust and can be effectively terminated by TF pathway inhibitor.
How is the cell based model amplified (amplification step)?
(2)
Since the amount of thrombin generated is not sufficient, therefore numerous positive feedback loops are present that bind thrombin with platelets
Thrombin that is generated in the initiation phase further activates factor V and factor VIII, which serves as a cofactor in prothrombinase complex and accelerates the activation of FII by FXa by FIXa, respectively
What is the propagation step in the cell based model?
(2)
The accumulated enzyme complexes (tenase complex and prothrombinase complex) on platelet surface support robust amount of thrombin generation and platelet activation
This ensures continuous generation of thrombin and subsequently fibrin to form a sufficiently large clot
What is the stabilisation step of the cell based model?
(2)
Thrombin generation leads to activation of factor XIII (fibrin stabilising factor) which covalently links fibrin polymers and provides strength and stability to fibrin incorporated in platelet plug
In addition, thrombin activates thrombin activatable fibrinolysis activatable fibrinolysis inhibitor (TAF) that protects the clot from fibrinolysis
What is anticoagulation
The inactivation of the pro-coagulant pathway
