00:01
Thrombolytics are a different drug category
that we use in coagulation cascades.
00:07
Now, thrombolytics are different from anticoagulants in that
they are active against clots that have already formed.
00:14
So thrombolytics are a completely different class of drugs.
They catalyze conversion of plasminogen to plasmin,
and plasminogen to plasmin causes breakdown of fibrin.
So the fibrin blood clot is actually broken down.
00:29
It is used often in acute stroke after you've confirmed
that there is no hemorrhage on the CT scan.
00:36
We also use it in acute MI but that's more replaced by
catheterization. Adverse events of course are bleeding
and intracerebral hemorrhage. Now, I'm going to give you
a clinical pearl that won't be useful on your exam
but it's going to be useful in the real world. When you
have a person who has an acute intracerebral hemorrhage,
they will tell you somebody hit me in the back of the head
with a baseball bat. They are so emphatic about how swiftly
the headache came on and how severe it is that it's quite
shocking. And I had a patient when I was a medical student
who was put on a thrombolytic and they ended up developing
an intracerebral hemorrhage. She told me it was as if
somebody came and hit her on the back of the head.
We were quick, we consulted neurosurgery, we put a Burr hole in,
drilled a hole in her skull and took of the pressure and
we preserved brain function and she lived.
01:30
Had we not done that quickly within at least an hour of
treating the patient that patient would have died.
01:39
So, clinical pearl, intracerebral hemorrhage from these
drugs, treat it very quickly with neurosurgery consult.
01:48
Streptokinase is the prototypical drug and generally on exams
we'll talk about streptokinase but we also talk about other
ones in the real world. It does not show an affinity for
fibrin-bound plasminogen. There are tPA analogues
which are replacing streptokinase and they show affinity for
fibrin bound plasminogen. Alteplase is the prototypical drug
with the tPA analogues. Tenecteplase is a recombinant variant of human tPA that has a longer duration of action and has now become
probably the most commonly used thrombolytic out there.
02:24
Reteplase is another recombinant variant of human tPA which has a
faster onset and longer duration, and may end up replacing
the other drugs. Let's talk about procoagulants.
02:35
Let's talk about drugs that are given to patients who are
bleeding excessively and we need to fix it.
02:41
We'll start of first with vitamin K. So if you remember when
we were talking about warfarin, I was telling you that warfarin
inhibits vitamin K dependant clotting. Well, if you give
more vitamin K, you are going to reverse that effect.
02:55
Remember that vitamin K is fat soluble. So A, D, E, and K are
fat soluble vitamins. Remember that most vitamin products
will contain vitamin K even though they don't list it on the
bottle, and that's because it's hard to extract vitamin K
from vitamin A, D, and E.
03:12
So vitamin K is activated through the liver.
03:16
Replacement factors also include fresh plasma,
purified human clotting factors. And they can be factor VIII
concentrates for patients who have hemophilia A
and factor IX concentrates for patients who have hemophilia B.
03:31
Octaplex and Beriplex are mixture of factors. Factor II, VII,
IX, X, protein C. These are used in mixed coagulation deficiencies
and in patients who have overdosed on the novel
anticoagulant drugs, like rivaroxaban and apixaban.
03:51
There is a brand new class of drugs that you need to know
about. They are called the monoclonal antibodies.
03:56
They are going to completely change medicine. One of the first
ones that are out in terms of coagulation is idarucizumab,
or Praxbind. These monoclonal antibodies are completely changing the way
that medicine is being practiced in every single field.
Hematology has Praxbind. It binds directly to the agent
that is causing the anticoagulant defect. It is very very effective
and has minimal side effects. Other procoagulants include the
vasopressin agonists. Desmopressin is used commonly as a V2
agonist. It increases the concentration of von Willebrand's
factor and the factor VIII. And it's also used to prepare
hemophilia A patients or von Willebrand's patient for surgery.
04:43
Antiplasmin agents are also procoagulants. Procoagulant Amicar,
or aminocaproic acid and these other agents are orally taken.
04:52
can be administered either orally or intravenously.
04:55
They inhibit fibrinolysis by inhibiting plasminogen activation.
They increase the concentration of von Willebrand's factor
and the factor VIII. They are used to treat hemophilia.
They are used for prophylaxis in those high risk patients,
and they are used in post-op bleeding. And the most common
place where you are going to see them as a student
or as a physician is in post-op bleeding cases. In terms of
exams, it's important to know aminocaproic acid
as the prototypical drug and that's the one
that we are going to be using on questions.