title: Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors.
abstract: Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.
authors.affiliation: Department of Pathology GRJ235, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Van Cott
authors.affiliation: Department of Pharmacy, University of California Davis Medical Center, Sacramento, California.
authors.forename: A Joshua
authors.initials: AJ
authors.lastname: Roberts
authors.affiliation: Department of Pharmacy, University of California Davis Medical Center, Sacramento, California.
authors.forename: William E
authors.initials: WE
authors.lastname: Dager
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D016903:Drug Monitoring / Q000379:methods*; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D007263:Infusions, Parenteral; D010314:Partial Thromboplastin Time / Q000379:methods; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D019095:Point-of-Care Systems; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013918:Thrombin Time / Q000379:methods
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban; C074619:bivalirudin