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Hello, my name is Paul Kim,
and I'm an assistant professor
at McMaster University in Canada.
This seminar will
focus on the
"Advances in Fibrinolysis", mostly
discussing the basic science
aspects of fibrinolysis research.
I will also discuss clinical
application of these findings
and thrombolytic therapy.
0:21
Coagulation and fibrinolysis exist
as a fine hemostatic balance.
The left side represents
the coagulation cascade,
which is shown by
the conversion of prothrombin
to thrombin.
Thrombin, the central
enzyme in coagulation
cleaves soluble fibrinogen
into insoluble fibrin clot.
The right-hand side represents
the fibrinolytic cascade,
which is shown by the conversion
of plasminogen to plasmin.
Plasmin, the essential
enzyme in fibrinolysis
digests insoluble fiber
in clots to soluble
fibrin degradation products, or FDPs.
0:58
The loss of this balance leads to
various pathological outcomes;
uncontrolled up regulation of
the coagulation cascade leads
to thrombotic diseases such
as deep vein thrombosis,
heart attacks, and ischemic strokes.
1:13
Alternatively,
uncontrolled up regulation
of the fibrinolytic cascade leads to
bleeding episodes or hemorrhaging.
1:21
Therefore, the positive
feedback systems
inherent to both the coagulation
and fibrinolytic systems
are regulated by
inhibitory mechanisms.
Thrombin generation is
down-regulated by the activation
of protein C to form activated
protein C. Plasmin generation is
down-regulated by the
activation of
thrombin activatable fibrinolysis inhibitor,
or TAFI, to generate TAFI a.
Central to activation
of protein C and TAFI
is the thrombin
thrombomodulin complex.
Thrombomodulin, a trans-membrane
protein expressed on the surface
of endothelial cells, bind with
thrombin, which then act to alter
the substrate specificity of
thrombin from a pro-coagulant state
to an anti-coagulant state.
