00:01
So when it comes to vascular diseases, how
are we gonna clinch that diagnosis and figure out
what's going on with our patients?
Just as we've said with every
single portion of this lecture,
it's very important to be a diligent detective
and really do a thorough history and chart review.
00:18
So, it's gonna be important to
look in our chart or ask our question
to our patients, 'have you had any kind of
aortic manipulation within the past 2 to 8 weeks?
If so, we're really thinking about
cholesterol emboli.
00:30
How about a patient coming in with mental
status changes and neurological abnormalities?
or a history of having a diarrheal prodrome?
If that’s the case, I'm really gonna be thinking more
about thrombotic microangiopathies like TTP or HUS.
00:44
And how about a patient who's coming in with
malignant hypertension, uncontrolled hypertension
with blood pressures as high as 180/120.
00:53
I'm really going to be thinking about a renal
associated TMA for malignant hypertension.
00:58
Physical exam can also be very helpful for
us when it comes to diagnosing our patients.
01:03
So somebody coming in with cholesterol
emboli may have things like livedo reticularis
again as seen in this photo here.
01:11
They could also have something
called blue toe syndrome.
01:15
So sometimes, when you're doing aortic manipulation
or manipulation of any of those large arteries,
you can have a massive amount of
cholesterol emboli that will embolize distally
and it can actually cause ischemia
to the entire extremity as seen here
With thrombotic microangiopathies, our patients
oftentimes can manifest with purpura and petechiae,
and that makes sense because
they have thrombocytopenia
And of course, with malignant hypertension, our patient
will be coming in with very high blood pressures,
typically with end-organ damage
and blood pressures greater than 180/120
Laboratory evaluation is also important.
01:57
In cholesterol emboli syndrome, we can see things
like low complements because complement is activated.
02:02
We have recruitment of inflammatory cells into
those vessels where the ischemia is happening.
02:08
We can also if we have the right time, we can see that
peripheral eosinophilia which can be very helpful.
02:14
And then when we look at the
urine analysis, it's typically bland
but if we're lucky enough, we can actually
see a cholesterol crystal in there as well.
02:22
Again, I want to underscore the
importance here because looking at that urine,
if I don't see muddy brown
cast as I would see in ATN,
this is very helpful again to distinguish
between the entity of radiocontrast exposure
from ATN and renal atheroembolic
disease from cholesterol emboli.
02:41
So, for a laboratory evaluation forTMA, we can
see things like thrombocytopenia - low platelets.
02:48
We can see schistocytes
on the peripheral smear.
02:51
So remember what is happening,
we have those platelet thrombi,
we have problems with the red blood
cells kind of going through in being lysed
so you have intravascular
hemolysis as shown here,
and our urine analysis
may have red blood cells.
03:05
So when it comes to treatment of our patients who
has the TMAs, it's really gonna depend on the cause.
03:11
So for renal atheroembolic disease,
or cholesterol emboli syndrome,
it's unfortunate because we don't have
a lot of therapies that can help to mitigate
the response of what's going on other
than just treating our patient supportively.
03:22
That means that what I want to do is I need to
ensure that nothing else happens to that patient
in order to progress their disease.
03:29
So I want to avoid things like nephrotoxic exposures
and make sure my patient's blood pressure is controlled.
03:37
If my patient has vasculitis then I'm really
going to target that underlying cause or condition
And then treat them specifically with immune-mediated
therapy that targets that particular condition.
03:50
For thrombotic microangiopathies again, it’s gonna be
very dependent on the condition that's manifesting.
03:56
If my patient has TTP, I'm
going to do plasma exchange
where I can actually remove those autoantibodies
that are affecting that ADAMTS13 activity
so that von Willebrand factor can be cleaved.
04:12
For Shiga-toxin associated HUS, that's the one
remember we talked about with the diarrheal prodrome.
04:18
Unfortunately there's nothing that we
can do other than provide supportive care
but that's gonna be critical in that
population again to make sure that my patient
has adequate volume status and make sure
that they don't have nephrotoxic exposures.
04:30
For complement-mediated TMA, this is
probably one of the most exciting topics
If those patients do in fact have a genetic
mutation or an autoantibody that they've acquired
that again is causing this
constitutive activity at c3 convertase,
we actually have a therapy available
now which is a monoclonal antibody to C5
and can actually prevent formation
of that membrane attack complex.
04:53
So it's pretty exciting although
I have to say, it's very costly.
04:57
And then finally for the drug induced TMA, we simply
remove the offending agent or the offending drug.