00:01
What are the causes of DVT? Well, the… probably
the most famous pathologist in the 19th century
was Rudolf Virchow here in Germany. Virchow
noted that three conditions were needed in
order for blood clots to form inside a blood
vessel, particularly the vein. First of all,
there had to be decreased flow—stasis—such
as happens, for example, from standing a long
time; the blood tends to pool in the legs.
The second is hypercoagulability. That is,
the blood has to have a tendency to clot that's
above normal. And finally, there needs to
be an injury to the endothelium—to the inner
lining of the vein—so that a blood clot
can start to form there and propagate and
get larger and eventually, of course, in a
significant percentage of people, break off
and embolize to the lung.
00:59
So circulatory stasis is alterations in normal
blood flow with decreased flow, with a tendency
of the blood flow to stay in one place. Endothelial
injury or dysfunction: That can be due to
trauma. It can be due to surgery, with vessel
piercings or damage. And, of course, it can
also be due to toxic substances—for example,
things contained in cigarette smoke. Finally,
hypercoagulability is an increase in the constitution
of the blood so that it increases its propensity
to clot. This is seen, for example, very,
very strongly in patients with cancer. When
patients have cancer the coagulation system
is markedly activated.
01:51
Here are a number of different kinds of ways
that you can have hypercoagulability. Many
of these are inherited. Cancer, of course,
is not an inherited one, but there are a number
of inherited ones. First of all, there can
be nat… the lack of a naturally occurring
inhibitor of blood clotting: protein C or
protein S. These prevent us from having constant
clotting going on in our blood system all
the time. If you're born with a decreased
amount of protein C or protein S, you will
have an increased tendency to clot. There
are also naturally occurring abnormal coagulation
factors. One of the most famous ones is called
factor V Leiden, discovered by medical scientists
in Leiden, Netherlands. Or there is a… an
abnormal prothrombin, and each of these are
factors in the clotting cascade, which is
a whole series of chemical reactions that
leads to a blood clot. And if one of… or
more of them are abnormal, it markedly increases
the tendency of spontaneous clotting.
02:56
The frequency of recurring DVT and pulmonary
embolism increases by a factor of two in patients
with inherited hypercoagulability states.
To say it another way, if you had one of these
abnormalities in the clotting system, you
will have 2 chances in 100 of developing recurring DVT/PE,
which is much higher than what… the 1 in
1,000 in the natural population. But most
patients with these abnormalities never experience
an intravascular thrombotic event, so it doesn't
make sense to try and find out everybody in
the society and treat them with blood thinners,
because you'd have many more hemorrhages than
you'd prevent DVT. So what we do is, when
a patient develops DVT or pulmonary embolism,
we check for a factor, because if they do
have that factor, we know they have an increased
risk of having the DVT / pulmonary embolism
repeat, and consequently, those patients go
on blood thinners for life. But most patients
with these abnormalities will not have a problem.