Argatroban
Encyclopedia
Argatroban is an anticoagulant
that is a small molecule direct thrombin inhibitor
. In 2000, argatroban was licensed by the Food and Drug Administration
(FDA) for prophylaxis or treatment of thrombosis
in patients with heparin-induced thrombocytopenia
(HIT). In 2002, it was approved for use during percutaneous coronary interventions
in patients who have HIT or are at risk for developing it.
Argatroban is given intravenously and drug plasma concentrations reach steady state in 1-3 hours. Argatroban is metabolized in the liver
and has a half-life
of about 50 minutes. It is monitored by PTT
. Because of its hepatic metabolism, it may be used in patients with renal dysfunction. (This is in contrast to lepirudin
, a direct thrombin inhibitor that is primarily renally cleared).
is chosen as the long term anticoagulant, this poses particular challenges due to the falsely elevated prothrombin time
and INR caused by argatroban. The combination of argatroban and warfarin may raise the INR to greater than 5.0 without a significant increased risk of bleeding complications. One solution to this problem is to measure the chromogenic factor X level. A level < 40-45% typically indicates that the INR will be therapeutic (2-3) when the argatroban is discontinued.
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
that is a small molecule direct thrombin inhibitor
Direct thrombin inhibitor
Direct thrombin inhibitors are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin. Some are in clinical use, while others are undergoing clinical development...
. In 2000, argatroban was licensed by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) for prophylaxis or treatment of thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
in patients with heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia is the development of thrombocytopenia , due to the administration of various forms of heparin, an anticoagulant...
(HIT). In 2002, it was approved for use during percutaneous coronary interventions
Angioplasty
Angioplasty is the technique of mechanically widening a narrowed or obstructed blood vessel, the latter typically being a result of atherosclerosis. An empty and collapsed balloon on a guide wire, known as a balloon catheter, is passed into the narrowed locations and then inflated to a fixed size...
in patients who have HIT or are at risk for developing it.
Argatroban is given intravenously and drug plasma concentrations reach steady state in 1-3 hours. Argatroban is metabolized in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and has a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of about 50 minutes. It is monitored by PTT
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...
. Because of its hepatic metabolism, it may be used in patients with renal dysfunction. (This is in contrast to lepirudin
Lepirudin
Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor.Brand name: Refludan, Generic: Lepirudin rDNA for injection.Lepirudin is a recombinant hirudin derived from yeast cells. It is almost identical to...
, a direct thrombin inhibitor that is primarily renally cleared).
Transitioning to warfarin in individuals with heparin induced thrombocytopenia
Argatroban is used as an anticoagulant in individuals with thrombosis and heparin induced thrombocytopenia. Often these individuals require long term anticoagulation. If warfarinWarfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
is chosen as the long term anticoagulant, this poses particular challenges due to the falsely elevated prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
and INR caused by argatroban. The combination of argatroban and warfarin may raise the INR to greater than 5.0 without a significant increased risk of bleeding complications. One solution to this problem is to measure the chromogenic factor X level. A level < 40-45% typically indicates that the INR will be therapeutic (2-3) when the argatroban is discontinued.