This study describes the present knowledge regarding the clinical application of
argatroban, a direct competitive
thrombin inhibitor for
heparin-intolerant patients, including those with congenital and acquired
antithrombin III deficiencies, those with
heparin-induced
thrombocytopenia, and those with high levels of polymorphonuclear
granulocyte elastase. These patients are often associated with intracircuit clot formation with
heparin anticoagulation during
extracorporeal circulation. Therefore,
argatroban may be chosen as one of the alternate
anticoagulants. Because the
anticoagulant effect of
argatroban is reflected in the prolongation of activated
thromboplastin time, monitoring is easy, similar to that for
heparin. Because
argatroban has a fast acting
anticoagulant effect without any cofactors such as
antithrombin III, this
drug is a favorable
anticoagulant for
heparin-intolerant patients with
antithrombin III deficiencies requiring
extracorporeal circulation. In adverse reactions to
heparin,
heparin acts as an
antigen after complexing with
platelet factor 4, which leads to life-threatening
heparin-induced
thrombocytopenia. As
argatroban prevents
heparin-induced platelet aggregation, it is effective for use as a therapeutic
anticoagulant. In other clinical applications,
heparin decreases
antithrombin activity and causes intracircuit clot formation during
extracorporeal circulation when the polymorphonuclear
granulocyte elastase level is very high. The
antithrombin activity shows less decrease when
argatroban is substituted for
heparin. These findings indicate that
argatroban is a useful alternative
anticoagulant in these
heparin-intolerant patients.