The coagulation cascade burns us precious!!!

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i61164

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About three lines into the following explanation, my brain just shuts down.


The coagulation cascade can be summarised as follows:

Tissue Factor pathway: the main role of the tissue factor pathway is to generate a "thrombin burst," thrombin being the single most important constituent of the coagulation cascade in terms of its feedback activation roles. FVIIa circulates in a higher amount than any other activated coagulation factor and following damage to the blood vessel endothelium Tissue Factor (TF) is released, this then forms a complex with FVIIa (TF-FVIIa) this activates FIX and FX. FVII itself is activated by thrombin, FXIa, plasmin, FXII and FXa. The activation of FXa by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). FXa and its co-factor FVa form the prothrombinase complex which activates prothrombin to thrombin. Thrombin then activates other components of the coagulation cascade, including FV and FVII (which activates FXI which in turn activates FIX), and activates and releases FVIII from being bound to vWF. FVIIIa is the co-factor of FIXa and together they form the "tenase" complex which activates FX and so the cycle continues.
Contact Activation pathway: There is formation of the primary complex on collagen by high molecular weight kininogen (HMWK), prekallikrein and FXII (Hageman factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the tenase complex which activates FX to FXa. The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK and prekallikrein do not have a bleeding disorder.
Thrombin Thrombin has a large array of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a haemostatic plug. In addition, it activates Factors VIII and V and their inhibitor protein C (in the presence of thrombomodulin), and it activates Factor XIII, which forms covalent bonds that crosslink the fibrin polymers that form from activated monomers.
Following activation by the contact factor or tissue factor pathways the coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex, until it is down regulated by the anticoagulant pathways.

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About three lines into the following explanation, my brain just shuts down.


The coagulation cascade can be summarised as follows:

Tissue Factor pathway: the main role of the tissue factor pathway is to generate a "thrombin burst," thrombin being the single most important constituent of the coagulation cascade in terms of its feedback activation roles.

FVIIa circulates in a higher amount than any other activated coagulation factor and following damage to the blood vessel endothelium Tissue Factor (TF) is released, this then forms a complex with FVIIa (TF-FVIIa) this activates FIX and FX.
FVIIA + TF(following damage Tissue Factor released) = TF-FVIIa
TF-FVIIa = activation of FIX and FX

FVII itself is activated by thrombin, FXIa, plasmin, FXII and FXa. The activation of FXa by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI).

FXa and its co-factor FVa form the prothrombinase complex which activates prothrombin to thrombin.
FXa + FVa = prothrombinase complex (activates prothrombin to thrombin)

Thrombin then activates other components of the coagulation cascade, including FV and FVII (which activates FXI which in turn activates FIX), and activates and releases FVIII from being bound to vWF.

Thrombin activates the above steps


FVIIIa is the co-factor of FIXa and together they form the "tenase" complex which activates FX and so the cycle continues.
FVIIIa + FIXa = tenase" complex = activation of FX


Contact Activation pathway: There is formation of the primary complex on collagen by high molecular weight kininogen (HMWK), prekallikrein and FXII (Hageman factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into FXIa.

Factor XIa activates FIX

FIXwith its co-factor FVIIIa form the tenase complex which activates FX to FXa.

The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK and prekallikrein do not have a bleeding disorder.


Thrombin has a large array of functions.
Its primary role is the conversion of fibrinogen to fibrin,
fibrin - building block of a haemostatic plug.
it activates Factors VIII and V and their inhibitor protein C (in the presence of thrombomodulin),
activates Factor XIII, which forms covalent bonds that crosslink the fibrin polymers that form from activated monomers.
Following activation by the contact factor or tissue factor pathways the coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex,
continues until it is down regulated by the anticoagulant pathways.

Tried my best to break it down a little... I'm not in med school by any means... if I completely messed this up..I apologize...
 
Draw A Flowchart !
 
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About three lines into the following explanation, my brain just shuts down.


The coagulation cascade can be summarised as follows:

Tissue Factor pathway: the main role of the tissue factor pathway is to generate a "thrombin burst," thrombin being the single most important constituent of the coagulation cascade in terms of its feedback activation roles. FVIIa circulates in a higher amount than any other activated coagulation factor and following damage to the blood vessel endothelium Tissue Factor (TF) is released, this then forms a complex with FVIIa (TF-FVIIa) this activates FIX and FX. FVII itself is activated by thrombin, FXIa, plasmin, FXII and FXa. The activation of FXa by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). FXa and its co-factor FVa form the prothrombinase complex which activates prothrombin to thrombin. Thrombin then activates other components of the coagulation cascade, including FV and FVII (which activates FXI which in turn activates FIX), and activates and releases FVIII from being bound to vWF. FVIIIa is the co-factor of FIXa and together they form the "tenase" complex which activates FX and so the cycle continues.
Contact Activation pathway: There is formation of the primary complex on collagen by high molecular weight kininogen (HMWK), prekallikrein and FXII (Hageman factor). Prekallikrein is converted to kallikrein and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the tenase complex which activates FX to FXa. The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of FXII, HMWK and prekallikrein do not have a bleeding disorder.
Thrombin Thrombin has a large array of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a haemostatic plug. In addition, it activates Factors VIII and V and their inhibitor protein C (in the presence of thrombomodulin), and it activates Factor XIII, which forms covalent bonds that crosslink the fibrin polymers that form from activated monomers.
Following activation by the contact factor or tissue factor pathways the coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex, until it is down regulated by the anticoagulant pathways.

Yeah, a flowchart is your best bet. Forget the F -blah blah notation. Go with numbers. Factor 12 becomes 12a after being exposed to vascular changes. 12a has enzymatic activity, and converts factor 11 to 11a, and so on. It's not too bad once you put about 10 minutes into thinking about it.

Here's a simplified flowchart that might help?
http://www.aafp.org/afp/20010801/419_f1.gif

Good luck!
 
omg u evil evil person! now i can't rest till i get those pathways in my head!
 
Ugh, it's almost as bad as complement!

At least complement goes in numerical order. The coagulation pathway just makes no sense--probably the product of some PhD's narcissism.
 
just be glad you didn't have to come up with that.



Wait until phys next semester, it's more understandable, just memorize it now. (Then they re-explain it in path). Then there's an awesome guy who teaches it -- Hartmut Weiler. There are also hilarious coops from 2008 from the lecture. I don't get coops, but I got copies of those.
 
I took immunology in undergrad and she made us memporize that thing.
 
Wait until phys next semester, it's more understandable, just memorize it now. (Then they re-explain it in path).

I am learning this for the 3rd time: now in path, previously in undergrad and med 1 phys.

And every time I pick it up again, it seems like I've never seen it before. :rolleyes:
 
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