Somethings I never quite understood about anticoagulation...

[quietmedic]

Hey all. Something I never totally understood about anticoagulation.

There are so many different pathways that we can play with (vitamin K, antithrombin III, direct thrombin, platelet adhesion, etc...)

I never quite understood...why we choose one over the other? And more so never understood...if we suppress just one, let's say coumadin for Vitamin K factor suppression, why wouldn't the other pathways compensate, defeating our efforts? Doesn't the body naturally compensate for deficiencies? Wouldn't we have to suppress all at the same time in order to effect a change in coagulation?

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[HoldTheCoffee]

How exactly would the body compensate if synthesis of the coagulation factors is being inhibited by your medication?

 

[KLPM]

Hey all. Something I never totally understood about anticoagulation.

There are so many different pathways that we can play with (vitamin K, antithrombin III, direct thrombin, platelet adhesion, etc...)

I never quite understood...why we choose one over the other? And more so never understood...if we suppress just one, let's say coumadin for Vitamin K factor suppression, why wouldn't the other pathways compensate, defeating our efforts? Doesn't the body naturally compensate for deficiencies? Wouldn't we have to suppress all at the same time in order to effect a change in coagulation?

Because coagulation is much more complicated than the intrinsic/extrinsic pathways. It involves complex interaction of many contact surfaces.

http://www.hematologiacr.org/articulos/The cell based model of coagulation.pdf

 

[quietmedic]

How exactly would the body compensate if synthesis of the coagulation factors is being inhibited by your medication?

Well, multiple factors in multiple pathways...wouldn't another just take over? If you inhibit intrinsic, then extrinsif will jump in, an vice versa...if you inhibit common, then platelet aggregation could take up the slack...etc...

 

[HoldTheCoffee]

Well, multiple factors in multiple pathways...wouldn't another just take over? If you inhibit intrinsic, then extrinsif will jump in, an vice versa...if you inhibit common, then platelet aggregation could take up the slack...etc...

This sounds like a teological explanation, I'm not sure if I can think of any straightforward mechanisms/feedback loops in which the extrinsic pathway or intrinsic pathway or platelet aggregation etc., would "know" to pick up the slack. It's been a while since I studied the clotting cascade though.

Because coagulation is much more complicated than the intrinsic/extrinsic pathways. It involves complex interaction of many contact surfaces.

http://www.hematologiacr.org/articulos/The cell based model of coagulation.pdf

That might be the case, but that doesn't mean that there aren't critical steps in the coagulation pathway. Case in point, patients with hemophilia A have a predisposition to bleeding. For those patients, their major deficiency is in just one clotting factor in the intrinsic pathway. So at least for them, even if there is some compensatory activity in the extrinsic pathway, it clearly isn't enough to make up for the deficit. On the other hand, warfarin disrupts the synthesis of multiple clotting factors, including factors II and X which lie in the common pathway downstream of both the extrinsic and intrinsic pathways.

I dunno, makes sense to me why warfarin seems to do the trick for many patients but I definitely welcome further discussion.

 

[KLPM]

That might be the case, but that doesn't mean that there aren't critical steps in the coagulation pathway. Case in point, patients with hemophilia A have a predisposition to bleeding. For those patients, their major deficiency is in just one clotting factor in the intrinsic pathway. So at least for them, even if there is some compensatory activity in the extrinsic pathway, it clearly isn't enough to make up for the deficit. On the other hand, warfarin disrupts the synthesis of multiple clotting factors, including factors II and X which lie in the common pathway downstream of both the extrinsic and intrinsic pathways.

I am going to be honest I am not 100% sure what you are trying to say.

The article I posted about the "Cell-based model of coagulation" basically explains that:

1. The idea of "intrinstic" and "extrinsic" pathways is really a laboratory-based one and not representative of how coagulation really occurs in the body.

2. The "intrinsic" and "extrinsic" pathways are not separate redundancies but rather actually work in unison to generate factor Xa onto the relevant contact surfaces.

I know that medical students like myself often ask the question "how come in this condition when 1 coagulation factor is blocked the other paths don't take over". Well based on this model the answer is really because this "other path" is not really another path. They are really part of the same process.

Correct me if I am (very likely) wrong.

 

[HoldTheCoffee]

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