Coagulation Cascade Flashcards
what type of enzymes are most of the enzymes in the coagulation cascade?
serine proteases
they hydrolyze peptide bonds using a serine residue at their active center
what are the coagulation factors in the coagulation cascade?
II, VII, IX, X, XI, XII, and XIII
II = thrombin
what do cofactors do in the coagulation cascade?
they amplify the coagulation cascade
what are the cofactors in the coagulation cascade?
TF = tissue factor
TFV
TFVIII
usually just called “factors” too
what happens during the coagulation cascade?
the coagulation cascade is a series of factors which activate each other in a cascade fashion
the whole point of the cascade is to turn fibrinogen into fibrin, so we can seal up the platelet plug we just made
summary: TF help turn fibrinogen into fibrin
does your body usually use the extrinsic or intrinsic pathway to make fibrin?
the two pathways are big-time co-dependent
In vivo, we need to have both intrinsic and extrinsic pathways working correctly to make fibrin
what is the main activator of the intrinsic pathway in vivo?
thrombin
what is factor XII important for?
important in forming clots in test tubes
doesn’t play much of a role in vivo
what happens to people with deficiencies of high molecular weight kininogen, prekallikrein, and factor XII?
nothing!
they don’t have bleeding disorders!
these factors are not crucial for activation of the intrinsic pathway in vivo
what is the activator of the extrinsic pathway?
tissue factor
what is tissue factor?
membrane protein that is found:
- on cells that are normally not in contact with blood (like smooth muscle cells in the subendothelium and fibroblasts surrounding blood vessels). Vascular injury exposes this TF to the blood and initiates the coagulation cascade
- in microparticles
- on endothelial cells, and on monocytes, when there’s inflammation (but not under normal resting conditions – otherwise we’d be coagulating all over the place)
what are micorparticles?
tissue factor is found in microparticles
they are little fragments of cell membrane found in normal blood
these microparticles have receptors for P-selectin
P-selectin is a cell adhesion molecule that lives in platelets and endothelial cells
When it’s activated, it flips to the outside of the cell membrane, and the microparticles stick to it, and tissue factor accumulates in the region of the forming clot.
what does TF do?
TF binds to activated factor VII, and then this TF-VIIa complex kicks off the coagulation cascade via the extrinsic pathway
What factors are involved in the extrinsic pathway?
tissue factor and factor VII
What factors are involved in the intrinsic pathway?
factors XI, IX, and VIII
also involves factor XII, fibrinogen, prekallekarin and high molecular weight kininogen, although we don’t care too much about those because deficiencies in these don’t result in disease
what factors are involved in the final common pathway?
factors X, V, II (thrombin) and I (fibrinogen)
can be activated by either the intrinsic or extrinsic pathway
At what point in the coagulation cascade do both pathways converge?
At the activation of factor X
what are the steps that happen when a vessel is injured?
- first thing that happens is that tissue factor is exposed to the bloodstream, and the extrinsic pathway is activated
- TF binds to factor VIIa and then that TF-VIIa complex converts factor X to Xa
- Xa converts II to IIa
- IIa converts fibrinogen to fibrin
what happens when you make Xa via the extrinsic pathway?
as soon as we make a little bit of Xa using the extrinsic pathway, something called Tissue Factor Pathway Inhibitor (TFPI) shuts down the entire extrinsic pathway. Totally kills it
what happens after the extrinsic pathway has been shut down?
the small bit of thrombin that was generated on the way to making fibrin is able to activate the intrinsic pathway
thrombin converts XI to XIa
then the process continues down the intrinsic and final common pathways which results in the formation of fibrin
factors V and VIII really amplify the intrinsic and final common pathways, respectively
what does factor VIII do?
VIII –> VIIIa
VIIIa amplifies IXa
IXa activates X –> Xa
what does factor V do?
amplifies the final common pathway
V –> Va
Va amplifies Xa
Xa activates II –> IIa
what does thrombin do?
- activates fibrinogen (I) –> fibrin (Ia) reaction
2. it activates factor XIII, which crosslinks the fibrin molecules that have been incorporated into the platelet plug
At what event in the coagulation cascade do both intrinsic and extrinsic pathways combine to form the common pathway?
Conversion of factor X à Xa
