Thromboembolism is a common cause of death and disability.
Heparin or
warfarin, the current standard management for
thromboembolism may cause serious
bleeding complications.
Thrombin is the key
enzyme of coagulation.
Hirudin, the most potent natural
thrombin-specific inhibitor, was first isolated from leech salivary fluid. Synthetic
thrombin-specific inhibitors are rationally designed based on the knowledge on the structures of the activate site of
thrombin.
Thrombin-specific inhibitors are the current best choice for the treatment of
heparin-induced
thrombocytopenia (HIT). Recombinant
hirudins (such as
desirudin) were also approved for the prevention of
thrombosis after hip or knee surgery.
Bivalirudin (
hirulog-1 or
Angiomax), in adjunct to
aspirin, was approved for prevention of
thrombosis in patients with
unstable angina following angioplasty.
Argatroban has been used for the treatment of HIT, peripheral and cerebral thrombotic diseases. The benefit of using
thrombin-specific inhibitors alone in acute
myocardial infarction or
unstable angina remains uncertain. Some of
thrombin-specific inhibitors which are small molecules are orally active. The major concern for the use of
thrombin-specific inhibitors is
bleeding complication. The efficacy, safety, stability and oral bioavailability may be considerably improved through structural optimization. A growing line of evidence suggests that
statins, the most commonly prescribed
cholesterol lowering drug, may inhibit
thrombin generation.
Statins do not cause
bleeding and have an outstanding safety profile. The findings suggest that further development of
thrombin-specific inhibitors and exploration of the potential applications of non-specific
thrombin inhibitors, including
statins, may improve the prevention and management of thromboembotic events.