Here’s an important table to compare heparin versus warfarin.
Heparin, number one, large.
Warfarin, small lipid.
What does that mean to you?
Passes through the blood-placenta barrier.
Next, administration heparin, parenteral only, IV or subcutaneous.
Warfarin aka Coumadin, oral.
Site of action, heparin blood, warfarin why the liver?
The vitamin K-dependent factor is epoxide reductase.
Vitamin K epoxide-O is the abbreviation and then you have the letter C complex.
The onset of action is rapid with heparin, hence, it’s a bridge therapy
because you’re worried about heparin and protein CNS wanting got quickly.
So to prevent any type of necrosis, if possible, you start the heparin first.
Warfarin will take time for it to inhibit that enzyme.
The mechanism of action, heparin inhibits antithrombin III.
Warfarin, we talked about vitamin K-dependent factor and, specifically, epoxide reductase.
As for the duration of action, well, heparin will be acute whereas warfarin will be chronic.
Inhibition of your—well the teratogen that we talked about, in vitro.
Well, what’s amazing is this, heparin not only is it large and doesn’t cross the blood-brain barrier
but in terms of inhibition, coagulation in vitro heparin it will show it to you.
Warfarin, not so much because heparin work so quickly, antithrombin III.
Treatment of acute overdose protamine sufate,
whereas with warfarin you should be thinking about replenishing those vitamin K-dependent factors.
So maybe fresh frozen plasma or something called prothrombin complex concentrates or PCC.
How many letters in PCC?
One, two, three.
Now there are different types of PCC, you can have a 4 element or a 3 element.
Now what does that even mean?
Keep this mind, if I say prothrombin to you what branch of the coagulation pathway were you thinking?
If you’re thinking about extrinsic and you’re thinking warfarin,
you should be thinking about the vitamin K-dependent factors.
What are the four major prothrombotic agents?
II, VII, IX, and X.
You can have clinically PCC, prothrombin complex concentrate, but not as much factor VII in it.
So now I have left is II, IX and X.
That’s the one that you wanna know.
In other words what I’m trying to tell you is, you have a patient who is in a state of hemorrhage,
right? Too much anticoagulation.
You wanna replenish you coags, you give FFP or PCC.
Keep that in mind.
Monitoring, we talked about heparin will PTT.
Warfarin will be WEPT, W-E-P-T, W-E-P-T.
How many seconds for PT?
11 to 15 seconds.
You add a T, you add more time.
That time for PTT is 25 to 40 seconds.
You can use which one of these tests as well as a liver function test please.
PT, the site of action of warfarin is delivered.
And we talked about placenta crossing warfarin will wage war upon the fetus.
It’s a teratogen, do not use it.
Heparin can still be used during pregnancy.
Now we’ll take a look at thrombolytics.
Here’s your patient walking to the door.
The patient comes in and has chest pain, tachycardia, diaphoresis.
The pain is radiating up to the jaw, substernal, left side shoulder.
Take a look at the labs and you find an increase in troponin I
and upon let’s say ECG leads II, III in AVF and you find an ST elevation.
And at this point you’re thinking most likely transmural type of infarction
taking place of the right coronary artery, obviously, have a myocardial infarction.
At this point your objective as a clinician is to make sure that you bust this clot as quickly as possible.
Welcome to thrombolytics.
Now, you may either convert directly or indirectly.
The enzyme here of course would not be fibrin nor gonna be thrombin.
You bring it to discussion the conversion of plasminogen into plasmin
and this plasmin is then going to break up this clot very, very quickly, isn’t it?
Now, what’s really fascinating about this is the fact that you would find an increase in PT, PTT
when you’re using a thrombolytic.
There’s every possibility that you may also bring about reperfusion injury, do you remember that?
But the discussion reperfusion injury is all about risks and benefits and if you know the time is salvation,
in other words 3 hours,
if you’re able to get in there and bust that clot
the amount of damage that you’re going to cause to the heart and to the tissue
would be rather minimal, correct? Reperfusion injury.
Now with all that said, you use a thrombolytic, you create or activate your plasmin,
however, what’s never going to decrease when you use a thrombolytic,
obviously, is a no change in platelet count.
But you may have an increase in PT, PTT though because the coagulation factors are busy.
The clinical use here would be obviously myocardial infarction,
however, the toxicity becomes important.
You may result to massive, massive type of bleeding.
Now, what you really wanna be careful of is, as far as you’re concerned,
remember you’re not in practice yet,
you when you become let’s say a neurosurgeon,
then you do what you want in terms of your patient knowing what the consequences are.
However, at this point the standard is contraindicated in patients with active bleeding up to a,
contraindicated in patients with history of intracranial bleeding,
contraindicated in recent surgery or if there’s a known bleeding diatheses.
For example, your patient has DIC or obviously severe hypertension.
Now if there is toxicity that you’re worried about with providing thrombolytic
and you have too much, too much bleeding then I’m gonna show you in a diagram upcoming
the mechanics of aminocaproic acid which is then going to be inhibitor of fibrinolysis.
So there’s some important antidotes, aren’t there, that we talked about does for with heparin.
What is it called?
Protein or protamine sulfate, number one.
With warfarin you wanna replenish the coagulation factors.
Fresh frozen plasma or prothrombin complex concentrates.
If it’s TPA, then we’re gonna talk about tissue plasminogen activators
either direct or indirect and you’re thinking about aminocaproic acid.
Let’s take a look at that diagram.
Let me set this up for you.
The objective of this entire diagram is to make sure that you bust this clot.
I want you to take a look at where we are down at the bottom here.
Do you see the word fibrin, please?
Well, can you picture a clot with fibrin?
Can you picture that for me?
Remember that fibrin it was acted upon by thrombin and it was in between the glycoprotein IIb/IIIa
and you formed a stable inside of a clot.
That’s what you’re dissolving.
Are we clear?
In order to dissolve this clot then you need to activate, whom?
Now you go to the top, take a look at plasminogen.
So our objective is to take this clot that had fibrin
is to activate plasminogen into plasmin and look what plasmin’s doing.
Right there, smacked in the middle.
Do you see that?
That plasmin is taking the fibrin which is the clot form right now and dissolving it.
Now, what do we call this clinically?
How do we know if we are breaking down clot?
How do you know?
You’re looking at a lab test in your hand or on a screen,
how do you know that you know that the clot is being broken down?
You’re looking for D-dimers.
So what are D-dimers specifically?
You must know the D-dimers are not fibrinogen but fibrin split products.
So you can expect whenever plasmin when it’s activated and it’s breaking down your fibrin,
no doubt, you would expect to find D-dimers.
Now, what are different ways in which you can use a thrombolytic or what are the thrombolytics?
They will activate plasminogen.
On your left you’ll notice we have activators, either direct or indirect.
These activators include, while you’re focusing upon the suffix A-S-E.
I don’t wanna say it out loud because it sounds like ace.
I don’t wanna do that because it’s going to confuse you, right?
Because whenever you think about ACE inhibitors, obviously,
you’re talking about enalapril and so on so forth but I want you to be able to identify A-S-E
and when you do so, then this is going to be your plasminogen activators.
This include alteplase tPA, tissue plasminogen, or reteplase or streptokinase or tenecteplase.
I said earlier in the previous discussion contraindications.
If you find that your patient has previous surgery,
is in a state of bleeding, that is an intracranial bleeding,
then these drugs will be contraindicated.
Is that clear?
Let’s say that there is toxicity with too much bleeding and I told you that there would be an antidote
and that antidote would be one in which it would inhibit fibrinolysis
by inhibiting the conversion of plasminogen into plasmin.
Take a look over to the right and I need you to focus on aminocaproic acid.
So that would be your antidote as far as if you have a patient who’s suffering from TPA toxicity.
By TPA, I’m referring to tissue plasminogen activator. These are your thrombolytics.