Chapter 4: Coagulation factors Flashcards
(20 cards)
What is the coagulation cascade?
The coagulation cascade is a series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot
Fill in: Each reaction step (of the coagulation cascade) involves an …. (an activated coagulation factor), a …. (an inactive proenzyme form of a coagulation factor), and a …. (a reaction accelerator).
enzyme, substrate and cofactor respectively
Components (enzyme/substrate/cofactor) are assembled on a negatively/positively charged phospholipid surface
Negatively
Assembly of reaction complexes also depends on a certain ion… which one? And how does it work?
Calcium, it binds to y(gamma)-carboxylated glutamic acid residues that are present in factors II, VII, IX and X
The coagulation cascade can be divided into two pathways (in the laboratory). What are these two?
Extrinsic and intrinsic pathways
How is the intrinsic and extrinsic pathway triggered in the laboratory?
Intrinsic: phospholipids, calcium and negative-charged substance (e.g. glass beads)
Extrinsic: phospholipids, calcium and a source of tissue factor
How is clotting triggered in vivo?
In vivo, tissue factor is the major initiator of coagulation, which is amplified by feedback loops involving thrombin.
What happens at the end of the coagulation cascade?
Thrombin converts fibrinogen to a fibrin clot
Will you please look at fig 4.7 :)
Yhesyes (and i’ll look at 4.8 while i’m at it tooo)
What does the proghrombin time (PT) assay do?
It assesses the function of the proteins in the extrinsic pathway (factors VII, X, V, II (prothrombin, and fibrinogen)
The time for a fibrin to clot is measured
What does the partial thromboplastin time (PTT) assay do?
It screens the function of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II and fibrinogen)
The time for a fibrin to clot is measured
Are PT and PTT a great way to evaluate coagulation factor function in patients?
Although they are great utility in evaulating the coagulation factors, they do not recapitulate the events that lead to coagulation in vivo
Thrombin has many qualities. What does it do?
for a visualizer see fig 4.9
- Conversion of fibrinogen into crosslinked fibrin.
- Platelet activation.
- Proinflammatory effects.
- Anti-coagulant effects.
The coagulation cascade sets another cascade in motion that limits the size of the clot. What is this cascade?
Fibrinolytic cascade
How is studied which factor is important in the cascade?
They evaluatie the symptoms (mild/severe bleeding e.g.) in patients with a factor … deficiency
Fibronolysis is largely accomplished through enzymatic activity. Which enzyme? And what does it do?
Plasmin (which breaks down fibrin and interferes with its polymerization)
An elevated level of breakdown products of fibrinogen (often called fibrin split products), most notably fibrin-derived D-dimers, are a useful clinical marker. What does it mark?
Several thrombotic states
What is the precursor of plasmin? How is it activated?
plasminogen, by factor XII-dependent pathway / plasminogen activators / t-PA
To conclude, how is the coagulation restricted to sites of vascular injury?
• limiting enzymatic activation to phospholipid surfaces provided by activated platelets or endothelium,
• circulating inhibitors of coagulation factors, such as anti-
thrombin III, whose activity is augmented by heparin-like
molecules expressed on endothelial cells
• expression of thrombomodulin on normal endothelial cells,
which bind thrombin and convert it into an anti-coagulant,
• activation of fibrinolytic pathways (e.g., by association of
tissue plasminogen activator with fibrin).
Will you also take a look at fig 4.10
OKok
