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0:00
Good morning, you all.
I'm Daniele Focosi.
I'm a hematologist and
transfusion physician at
the Pisa University
Hospital in Italy.
I'm going to talk to
you about the future of
plasma-derived medicinal
products or PDMP,
as we will shorten in
the rest of this talk.
0:21
I have no conflict
of interests to
disclose concerning the
topic of this talk.
0:29
I'm going to introduce
you to the table of
contents during
this one hour talk.
At first, we will
discuss the types of
PDMP and their main indications.
Then I will focus on the
Italian case study for
what concerns PDMP
usage and collections.
Then I will focus on
a special type of
PDMP which is COVID-19
convalescent plasma,
which is a topic of
utmost interests in
the last three years.
Finally, I will discuss
the perspectives for
the intravenous
immunoglobulins or
IVIG in the setting of COVID-19,
especially for the
immune-compromised patients.
1:20
At first, let's have a look at
the different types of PDMP.
The most used type is
definitively albumin,
which represents the main
protein in human serum.
Albumin has a half-life
as short as 12-16 hours,
and these are
commercially available
at two different concentrations.
The first one is
the isooncotic
formulation at 5%,
and the second formulation is
at 20-25% concentration,
so it is hyper-oncotic.
The main indications for
usage of albumins are
evacuative paracentesis,
high-volume therapeutic
plasmapheresis,
bacterial peritonitis, and as
a minor indications
albumin can also
be used in patients
with severe burns,
hemorrhagic shock,
major surgery,
protein-losing enteropathies,
and nephrotic syndrome.
The second most commonly use
PDMP, is immunoglobulins.
It is mostly used as an
intravenous formulation,
but it is increasingly used
as a subcutaneous formulation,
as we will see later.
There are three main
concentrations of immunoglobulins,
5, 10, and 50 g/l.
In commercially available
immunoglobulins
mostly consist of IgG
subclasses of immunoglobulin,
meaning that they are poorly
representative of IgA,
and IgM subclasses.
The main indications for
immunoglobulins are
primary and secondary
hypogammaglobulinemias as a
replacement therapy and at
high doses, the other
major indication
is instead autoimmune diseases.
The most common
autoimmune diseases are
ITP, Immune
Thrombocytopenic Purpura,
Guillain-Barre syndrome,
chronic inflammatory
demyelinating polyneuropathies
and Kawasaki syndrome.
These are the
official indications.
But most of the usage actually
stems from plenty
of off-label uses,
which is generating
scarcity of the product.
We are having in these
years a pipeline of
small molecules that will
hopefully reduce the demand
for immunoglobulins.
The main class is
the blockers of the
neonatal Fc receptor,
which basically
reduce the clearance
of the immunoglobulins
that are reinfused.
Then we have the third
major class of PDMP,
which are the clotting factors.
They are mainly used as
a replacement therapy in
patients with coagulopathies.
We have different types
of clotting factors.
The main two are Factor VIII
and Factor IX concentrates,
which are used for
hemophilia A and
hemophilia B respectively.
Factor VIII concentrates can
also include Von
Willebrand factor,
which is another very
important protein
for the stability
of coagulation.
Another side indication is
Von Willebrand disorder,
which is a different type
of inherited coagulant.
As you can see,
there are plenty of
different plasma derived
clotting factors
already available in the market.
But they are suffering
mounting competition from
recombinant clotting factors.
This basically means
that we can forecast a
reduction in the demand
for plasma-derived
clotting factors
from both recombinant
clotting factors
and upcoming gene therapies
for what concerns hemophilia.
But plasma-derived clotting
factors is not limited to
Factor VIII and IX
because we also
have prothrombin
complex concentrates,
which are also available
for different indications,
and we've quite a varied
formulation on the market.
Then we have other minor plasma
derived clotting factors,
such as antithrombin III,
and activated protein
C concentrates.
These do not represent
the majority of usage,
but can be somewhat
lifesaving so there
are often drugs
which can be very useful
in daily practice.
