The Assumption That Fibrinolysis and tPA Can Be Equated is Mistaken

Abstract

Case Summary
A 57-year-old gentleman was referred by GP
to our Acute Fibrinolysis is the body’s defense
system against obstructive blood clots, which
are responsible for conditions like heart attack
and stroke. This important endogenous function
is mediated not by one, but by two activators
called tissue plasminogen activator (tPA) and
urokinase plasminogen activator (uPA). Since
tPA was approved in 1987 and it binds to the
fibrin clot and induces fibrin-specific fibrinolysis.
By contrast, uPA was known since non-specifc
plasminogen activator which has no fibrin
affinity. Not surprisingly, tPA has invariably
dominated fibrinolytic therapy.
For example, in review articles dealing with
fibrinolysis, it is taken for granted that tPA is the
activator responsible so that it is often not even
mentioned. This is a well established concept
and a Google search of publications in which
Fibrinolysis is in the title, lists more than 350,000
citations in which tPA is assumed to be the
activator.
At the same time, two independent gene deletion
studies showed that, when the tPA gene was
deleted in animals, little change in the animals’
fibrinolytic effect took place. Since, when the
uPA gene was deleted, significant inhibition of
fibrinolysis occurred. When both of the activator
genes were deleted, fibrinolysis was arrested,
and extensive fibrin deposition was found in the
animals. It was concluded that both activators
were needed for normal function but that uPA
rather than tPA was the dominant activator [1,2],
contrary to the prevailing belief. However, these
findings had little influence on the prevailing idea
that tPA was responsible for fibrinolysis.