Speaker 1 (00:07):

It's time for another warm up. Let's get going, which glomerular disease should be suspected most in a
patient with each of the following findings. So first we have immunofluorescence shows a granular
pattern of immune complex deposition and light microscopy shows diffuse capillary thickening. So that
can be your OUS. Glom nephritis, uh, could also be diffuse proliferative glom nephritis. Next, we have
immunofluorescent shows that same granular pattern of immune complex deposition, but this time the
light microscopy shows hypercellular line. So this is acute post strep Cocal, uh, G low nephritis, and
those are inflammatory cells in the glumly. Next we have immunofluorescence shows a linear pattern of
immune complex deposition. So these are the anti GBM, uh, antibodies and good pasture syndrome.
Next we have em, shows sub endothelial humps and tram track appearance. That's gonna be your
member proliferative, glim nephritis. Next we have nephritis, deafness and cataracts. That's gonna be
your output syndrome. Next. We have Crescent formation in the glary eye. So this is gonna be seen in
the rapidly progressive glom nephritis, or, uh, also refer to as Crescent glim nephritis. Next, we have
segmental sclerosis, Andy on light microscopy. This is gonna be your, uh, focal segmental glom, low
sclerosis.

Speaker 1 (01:34):
Next we have anti GBM antibodies on immuno, uh, fluorescence. Uh, those are gonna be seen on the
good pasture syndrome. Again, Kim steel Wilson lesions are seen with diabetic nephropathy Pura on the
back of arms and legs, abdominal pain, IGA and nephropathy asking me the, uh, HEOC shown Uhura
spiking of the GMER basement membrane due to electron dense sub epithelial deposits. That's gonna
be your OUS glom nephritis, right? That brings us, uh, to the end of our warmup. Let's get to that
lecture. Now

Speaker 2 (02:09):
In this video, we're gonna talk about anticoagulant drugs. Nope, nothing funny about that. Let's get right
to it. Let's start with heparin. We said heparin is a co-factor for the activation of antithrombin, which
inactivates, thrombin and factor 10 a now antithrombin can work without heparin, but heparin makes it
something like a thousand times more active. So heparin supercharges antithrombin and heparin has a
very short halflife heparin can be used almost any time. You need anticoagulation, pulmonary embolism,
acute stroke, acute coronary syndrome, or MI D V T. And it can be used during pregnancy if you need
anticoagulation, because it does not cross the placenta. Now, how do we measure the effectiveness of
heparin? What lab do we monitor to make sure the blood is adequately anticoagulated or to make sure
it isn't too anticoagulated? Well, we monitor the PTT now for side effects. Any of these anticoagulant
drugs can lead to bleeding, obviously.

Speaker 2 (03:07):
So that can be a problem. Uh, heparin can cause bone loss, decreased bone formation in osteoporosis.
Uh, there's also a phenomenon known as heparin induced thrombocytopenia or H I T. Now if you have a
patient who's on heparin and the platelet count starts to drop either suddenly or gradually, and then
they eventually become thrombocytopenic. This is very, very suspicious for heparin induced
thrombocytopenia. Basically the way it works is that heparin binds to platelet factor four, and then you
get auto antibodies to that complex. And this auto-antibody complex can then go around and activate
platelets so that that's aggregate. Then they get removed from circulation and destroyed. Now it doesn't
happen all that often, and it doesn't happen to everybody less than 5% of patients on heparin will have
this. But the result is that these patients have thrombocytopenia, but at the same time, they're actually
in a hypercoagulable state.

Speaker 2 (03:55):
Now that's kind of counterintuitive. Uh, you might think that if the platelets are low, they're gonna be O
coagulable. But remember, these platelets are being activated and they're aggregating. So these
patients are forming platelet plugs and they're at risk for thrombosis. So what do you do for heparin? Do
thrombocytopenia. Well, you need to stop the heparin right away. That's the first thing. But remember
you have the patient on heparin for a reason. So you still want them to be anticoagulated. So now you
have to do something else because the patient's no longer at anticoagulate when you stop the heparin.
That brings us to the direct thrombin inhibitors, which are used to anticoagulate patients with H I T or
anytime you would normally use heparin, but it's contraindicated for some reason. Now there's one
group of thrombin inhibitors like drugs, like Lepar Rudin and Brudin and Des rutin.

Speaker 2 (04:38):
These are all derivatives of a peptide called her Rudin, which was originally found in the saliva of
leeches. Leaches sucked blood, right? So they need to be able to keep the blood flowing. So leaches
actually secrete a little anticoagulant in their saliva. It's actually pretty cool though. I'm not sure what
pharmaceutical genius was sitting around thinking. I need to come up with a new anticoagulate. I know
Lee bit, but anyway, her Rudin to inhibits thrombin, it's doing the same thing as antithrombin, but this
act, it acts actually at the same point in the coagulation cascade heparin doves, but it works through a
totally different mechanism. So Lepar rutin Brudin and Des rootin are all derivatives of Herin. Now there
are other direct thrombin inhibitors that aren't derivatives of. Herin including our turban and there's a
newer one called dabigatran. Now, anyway, if you have a patient with heparin induced
thrombocytopenia, you need to stop the heparin.

Speaker 2 (05:29):
Then you're gonna need to start a different anticoagulant. And some of these direct thrombin inhibitors
are approved for that use for treating heparin induced thrombocytopenia. Now you don't need to really
worry about which of these direct thrombin inhibitors are approved for which indications, but just know
if you have, have H I T you're gonna wanna switch to a direct Throid inhibitor. Initially, you wanna put
'em on warfarin because they're gonna need to be anticoagulate for an extended period of time because
of this for at least a month heparin. And a lot of these Throid inhibitors are IV drugs. They're not really
used for long term anticoagulation, but warfarin is an oral drug. So it can be used as an outpatient. So
you start your thrombin inhibitor. You wait for the platelets to come back up. Then once the platelets
get above a hundred, 150,000, you start warfarin.

Speaker 2 (06:09):
Then you can stop the thrombin inhibitor. Then also there are some low molecular weight heparin such
as the drug anox, which you may know better under the brand named lox. There's also da Parin and
several others. Now these are smaller than heparin. They have a lower molecular weight, and they act
mainly by stimulating antithrombin to inactivate factor 10 a rather than by inactivating thrombin. They
have a longer halflife than regular heparin. And they're usually given as subcutaneous injections twice a
day, sometimes just once a day, depending on what you're trying to do, are you trying to treat a DVT,
then you have to give it twice a day. If you're trying to prevent a D V T, which we call DVT prophylaxis,
you can use an Oxy Parin just once a day. So the dosing is a lot easier with these, and also you don't
have to monitor them.

Speaker 2 (06:53):
The lo molecular weight heparin dosing is weight based. So it doesn't have to be monitored with regular
heparin, which we call unfractionated heparin. It's often given IV, and you have to check the PTT six
hours after you started it, and then adjust the heparin dose and check again in another six hours. So it's
very high maintenance with these low molecular weight heparins. Not only do you only give it once or
twice a day, but your dose is based on the patient's weight. So you calculate your, then you don't have
to check any labs, but if for some reason you do wanna monitor it, you don't use the PTT. Instead, you
would check an anti factor, 10 a activity. Now, one last thing about these low molecular weight heparins
very important clinically is that they're not interchangeable. They have very different kinetics, uh, very
different dosing regimen, very different approved indications.

Speaker 2 (07:40):
And I can't imagine you're gonna be tested on that, but it will be important for you on the wards. And
there's also a drug called Fonda per that also works by activating antithrombin and inhibiting factor 10 a,
uh, so it's kind of like the lo Lac weight heparins, but it's technically not a heparin derivative. And then
there's yet another group of drug it's called the direct factor. 10 a inhibitors that I wanna mention very
briefly. These include drugs like RI uh rivaroxaban and a apixaban. And there are several more of these
drugs, uh, but anticoagulants are booming business. There's tons of these drugs coming out all the time.
When I was in med school 15 years ago, that was heparin. That was warfarin. And they had just started
developing the very first, low molecular weight heparin. And that was it. That was all we had.

Speaker 2 (08:19):
Now we've got about 10, low molecular heparins plus two or three entirely new classes of
anticoagulants. And each one of those classes has half a dozen different drugs in the class. But anyway,
rivaroxaban and AP apixaban are oral anticoagulants that work by inhibiting factor 10, a kind of like an
Oxy Parin they're sometimes used in AIB. They're also used to prevent post-op DV in patients who have
had knee or hip replacement. And if you look at the names of these, you see the letters X a right in the
middle, and that's gonna help you remember that these are factor 10, a inhibitors. The next drug to
discuss is warfarin or the brand name is cumin, which is the name you're gonna hear a lot. So it's one
brand name. You definitely wanna know, even though they're not gonna use that name on your test,
they'll say warfarin, but warfarin is definitely a high yield drug.

Speaker 2 (09:01):
Four stars, warfarin inhibits an enzyme called epoxide red reductase, which is responsible for recycling
vitamin K and vitamin K is used in the synthesis and gamma Caryl of vitamin K dependent cloting factors.
So warfarin prevents your liver from being able to manufacture these specific clotting factors. Now,
we've already talked about the vitamin K dependent cloting factors being factors 2 7, 9, and 10, and also
protein C and protein S so warfarin inhibits those factors, and that's gonna affect the PT the
prothrombin time. Now we use warfarin for chronic anticoagulation for a wide variety conditions. Atrial
fibrillation is a big one because the blood becomes stagnant in the left atrium. When the atrium isn't
contracting normally, and those AFib patients are at an increased risk of embolic stroke. We also use
warfarin for DVT prophylaxis or D V T treatment, and also PE treatment. Although I always tell patients
that the warfarin isn't really gonna dissolve the clot that's already there.
Speaker 2 (09:54):
Your body's gonna absorb that clot on its own over several weeks to months, we're just giving the
warfarin to prevent the clot from extending and warfarin is contraindicated in pregnant women,
because it does cross the placenta and it's agen specifically warfarin can cause bone and cartilage
problems in the EPIs and possibly some nasal hypoplasia incomplete development of the nose. So what
anticoagulant is safe in pregnancy heparin, or one of the low molecular weight heparins. Now heparin
and warfarin are two of the most commonly used classic anticoagulants. Like I said, they've been around
a long time. So let's take just a moment to review some basic differences between them. Heparin is an
IV or subcutaneous drug. It's an injectable drug warfarin and oral drugs. That's one reason we use
warfarin chronically instead of using heparin heparin has that short halflife. So you usually have to give it
continuously, like I said, you can check the PTT a few hours after a dose change and see whether you
achieve the desired effect.

Speaker 2 (10:49):
So it has these very rapid onset of action warfarin. On the other hand has a long half life, and it has a
very slow onset of action. It's only affecting the synthesis of new cloting factors. It doesn't do anything
to the cloting factors that are already out there in circulation. So you start warfarin and then you have to
wait two or three days before you're gonna see that INR start to change. And even then it's gonna take a
good five days before the INR is stabilized. So getting a patient on an appropriate therapeutic dose of
warfarin can take several days. And I said this in the previous video, but you just to reiterate, when you
first start warfarin, the first factors affected are actually protein, C and protein S especially protein C. So
when you first start warfarin, the patient's gonna become transiently hypercoagulable and that can lead
to some skin necrosis.

Speaker 2 (11:31):
And that's a bad thing. So when you start warfarin, the patient generally needs to be on either heparin
or an Oxy Parin to counteract transient hypercoagulability. And then once the INR is in the therapeutic
range, which is usually an INR of two to three, then you can stop the heparin or stop the inin and
continue the warfarin by itself. The other difference between heparin and warfarin that I wanna
highlight is the treatment of an acute overdose. So the reversal agent for heparin overdose is protamine
sulfate. So if somebody accidentally got too much heparin and you needed to reverse it quickly, you
would give protamine sulfate. Now you have to use it very carefully, because why are you putting the
patient on heparin to anticoagulate them? When you give protamine sulfate, it bind to the heparin and
it reverses the anticoag and that could lead to cloting, which is what you were trying to avoid in the first
place.

Speaker 2 (12:16):
And then for overdose of warfarin, you give oral or IV vitamin K. Now we don't give subcutaneous
vitamin K because it's not as effective. And actually IV vitamin K doesn't work any faster than oral
vitamin K does. And there's a small risk of anaphylaxis with the IV root. So I would recommend
<affirmative> oral vitamin K. It always seems like IV is gonna be faster than oral, but in this case, it really
isn't. The other thing about giving vitamin K is that it takes days to really do anything, to reverse the
effects of warfarin, right? You gotta wait for your liver to start making those cloting factors again. But
what if you have a patient who's bleeding to death right now, and you need to reverse the warfarin
quickly? Well, in addition to getting vitamin K, you can give prothrombin complex concentrate or PCC,
which is basically an infusion of the vitamin K dependent coagulation factors.
Speaker 2 (13:03):
Now, if PCC isn't available, you could give fresh frozen plasma, but PCC is considered first line for active
bleeding, due to warfarin and overdose. So for heparin overdose, you give protamine sulfate for, for an
overdose. You can get vitamin K and PCC. I don't always use warfarin, but when I do, I monitor the PT
and I and R stay anticoagulated. My friends. Then finally, let's quickly cover the thrombolytics
streptokinase uric kinases TPA, or autoplays, there's several of these different thrombolytic drugs too.
And these are your clot busting drugs. Why are they called clot busting drugs? Well, these thrombolytic
drugs activate plasma. And we talked about how plasma Mengen is converted to plasma, and then
plasma licenses, the fibro and clot. So plasma, degrades fi these thrombolytic drugs activate plasma. So
they bust up the clots by breaking down fi they're thrombo. They li thrombus, they li clots.

Speaker 2 (13:58):
Now, what do we use these? Well, we use them in early St. Elevation MI, but only if you're somewhere
out in the boonies and there's no cath lab for the most part, acute St. Elevation MI are gonna get
angioplasty and stenting and open up that vessel. But if that's not available, for whatever reason, you
can give TPA, that's gonna slice the thrombus, help refuge the heart. They also get used in treating an
acute stroke, but again, very early on when we talked about stroke, I mentioned that there are a whole
bunch of very specific exclusion criteria. Relatively few patients who come in with an acute stroke are
actually gonna be candidates for TPA. Then for side effects, if you break up clots, you're more likely to
bleed. So these are contraindicated in patients with active leading. And like I said, there are lots of
exclusionary criteria before you give thrombolytics.

Speaker 2 (14:41):
So you pull the drug out and then you go through this checklist of like 20 different things. They have this,
they have that. If they've been experiencing this, if any, one of those things is present, like maybe they
had surgery yesterday, you cannot give one of these drugs because the risk of complications outweighs
the benefit of the drug. So these are contraindicated in patients with active bleeding patients with any
history of intracranial bleeding, recent surgery, any known bleeding disorder, like maybe hemophilia or
severe hypertension. And then the reversal agent for these drugs is aminocaproic acid. Definitely that.
So that's it for the anticoagulant drugs. Now it's time for the intersection quiz.

Speaker 2 (15:18):
All right. First question. What lab test is used to monitor adequate anticoagulation in a patient taking
heparin and then a patient taking warfarin. So for heparin, it's the PTT, the partial thrombo plast time.
And then for warfarin, it's the PT, uh, the, the prothrombin time. And with that, the INR next, what are
the treatments for overdose of heparin and for warfarin, for heparin, you treat an overdose with
protamine sulfate. Then you treat warfarin overdoses with vitamin K and either PCC or fresh frozen
plasma. If there's active bleeding. And the last question, what's the treatment for heparin induced
thrombocytopenia. So the first thing, stop the heparin, and then you have to start a different
anticoagulant like LEPA Rudin or Gerban, uh, because these patients are now hypercoagulable due to all
that platelet activation. So they need to be on a different anticoagulant. And we've also got a few rapid
fire facts for you. The preferred anticoagulation for immediate anticoagulation is either gonna be
heparin or maybe low molecular weight heparin. Then the preferred anticoagulant for long term
anticoagulation is warfarin. And then the preferred anticoagulation during pregnancy is either heparin
or a low molecular weight heparin, but definitely not warfarin. That's it for now. I'll see you next time.