The coagulation cascade leads, via
thrombin activation, to the formation of
fibrin (from its precursor
fibrinogen) and platelet
thrombus. Several drugs are able to interfere with some of the enzymatic factors involved in
thrombin activation, but
thrombin inhibitors (
heparin,
hirudin and
hirulog [
bivalirudin]) are of particular interest because they disrupt the coagulation cascade by acting upon one of its final steps. Among the
thrombin inhibitors, oral
antithrombins (
ximelagatran) appear to hold great promise for the control of thrombogenicity in a number of clinical contexts. Oral
antithrombins do not require the participation of cofactors to exert their action, and in contrast to
thrombin inhibitors administered parenterally, they bind specifically to the active site of
thrombin without interfering with other portions of the molecule. Their specificity makes these drugs safe and obviates the need to monitor coagulability. Moreover, they show a low rate of interaction with other drugs or with foods, and the response to fixed doses is predictable. A number of clinical studies have investigated
antithrombins for prophylaxis prior to
orthopedic surgery, in the prevention of
cerebrovascular accidents associated with
atrial fibrillation, and in the control of
coronary artery disease. These studies have shown that
antithrombins are superior to other habitually used treatment options. Surprisingly, their use in long-term studies has not been associated with an increased rate of
bleeding events. Their interesting molecular characteristics and considerable therapeutic efficacy and safety suggest that oral
antithrombins will in the near future become a valuable therapeutic option.