Prolonged halflife of argatroban in patients with renal. Effects of argatroban as an anticoagulant for haemodialysis in patients with antithrombin iii deficiency. Antibodies that cause hit have been detected in up to 12% of patients with end stage renal disease. Heparin induced thrombocytopenia hit treatment page 1. Original article efficacy of argatroban in the treatment. A prospective comparison of three argatroban treatment regimens. After argatroban is discontinued, a repeat inr should be obtained 4 to 6. Note that argatroban is a nonformulary drug at uw medicine. A prospective comparison of three argatroban treatment. The dosing presented below is a guide to aid in the initiation of bivalirudin infusion.
Hit can be divided into two types, type i and type ii, with type i being a transient decrease in platelet count without clinical consequence. Argatroban for heparininduced thrombocytopenia in hepatorenal failure and cvvhd. The investigation focused on predictors for the maintenance doses of argatroban with efficacy and safety of argatroban being secondary outcomes. Argatroban inhibits thrombin with an inhibition constant ki of 0. Argatroban is a synthetic monovalent direct thrombin inhibitor indicated for prophylaxis and treatment of thrombosis in patients with hit. Effect of renal function on argatroban therapy in heparin. Angiotensinamideatenolol 1217 argatroban administration. Argatroban suggested guidelines for use university of washington medical center dept of pharmacy for physician use only this is not intended as a nursemanaged protocol september 2008 background.
Argatroban anticoagulant therapy in patients with heparin. Argatroban anticoagulation for renal replacement therapy. Heparin induced thrombocytopenia hit treatment page 1 of 7 disclaimer. Four consecutive patients with proven heparininduced thrombocytopenia hit, acute renal failure requiring continuous renal replacement therapy, and various levels of transient hepatic impairment. Stop all heparin including catheter flushes, enoxaparin or dalteparin, and warfarin obtain baselines labs if none in past 24 hours cbc, ptt, ptinr, basic metabolic profile, lfts. Our patient had apparently normal hepatic function at the initiation of dialysis, but the dosage of argatroban recommended by the manufacturer. Argatroban injection is indicated as an anticoagulant in adult patients with or at risk for hit undergoing percutaneous coronary intervention pci. Argatroban blocks the activity of certain clotting substances in the blood. Several different agents are currently available to provide effective anticoagulation in patients who have immunemediated hit. Following cessation of argatroban therapy in patients with normal renal and hepatic function, full reversal of anticoagulation occurs within 2 to 4 hours.
Argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparininduced thrombocytopenia hit. Argatroban for anticoagulation in continuous renal. Argatroban monohydrate drug bnf content published by. The secondary goal of the study will be to assess the adequacy of anticoagulation during hemodialysis. We recommend argatroban therapy for intensive care patients with hit, especially those with renal failure. Argatroban is highly selective for thrombin and has little or no effect on related serine proteases trypsin, factor xa, plasmin, and kallikrein. However, in all patients with suspected liver dysfunction due to recent elevation of liver transaminase levels and combined renal failure, a decrease in the initial dosage and careful titration of the infusion are mandatory. We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparininduced thrombocytopenia n 56 or history of heparininduced thrombocytopenia n 9. In general, with doses of argatroban up to 2 mcgkgmin, argatroban may be discontinued once the inr is greater than 4 while the patient is receiving combination therapy. Medical and surgical patients n 30 with acute or histories of heparininduced thrombocytopenia type ii and acute renal failure with necessity for crrt. In patients with acute dvt and severe renal failure, we suggest ufh over lmwh grade 2c if lmwh is used in patients with severe renal insufficiency for therapeutic anticoagulation, we suggest using 50% of the recommended dose grade. Argatroban is a synthetic, nonpeptide small molecular weight 500 da larginine derivative that reversibly inhibits thrombin by means of univalent binding to the active site exosite 3. Anticoagulants in renal impairment bc renal agency.
Two intensive care units medical and surgical of a university hospital. Argatroban therapy in heparininduced thrombocytopenia. Effects of argatroban as an anticoagulant for intermittent. We prospectively evaluated 3 treatment regimens of argatroban, a direct thrombin inhibitor, for providing adequate, safe anticoagulation in patients with endstage renal disease esrd during hemodialysis. Acova argatroban dosing, indications, interactions. From the international classification of diseases10th revision code, preexisting comorbidities included hypertension, dyslipidemia, diabetes mellitus, heart failure, chronic obstructive pulmonary diseases, chronic renal failure, and previous stroke. In patients with renal impairment o argatroban is not renally eliminated, and does not require initial dosage adjustments clinical conditions which may warrant dosing as low as 0. This algorithm has been developed for md anderson using a multidisciplinary approach considering circumstances particular to md andersons specific patient population, services. Renal impairment will not result in altered or delayed elimination. Argatroban renal dysfunction renal replacement therapy dialysis heparininduced thrombocytopenia. Argatroban is hepatically cleared and may be the preferred direct thrombin inhibitor in the presence of significant renal impairment, but conversely has prolonged effects in hepatic failure. Successful use of argatroban as a heparin substitute.
At therapeutic concentrations, argatroban has little or no effect on related serine proteases trypsin, factor xa, plasmin, and kallikrein. The effect of renal disease on the pharmacokinetics of argatroban was studied in 6 subjects with normal renal function mean clcr 95 16 mlmin and in 18 subjects with mild mean clcr 64 10 mlmin. Further cases of excessive anticoagulation have been reported in patients with multiple organ failure,3 and. Argatroban suggested guidelines for use university of. Heparininduced thrombocytopenia hit is a recognized complication of heparin and requires urgent detection and treatment. Argatroban is used to treat or prevent blood clots in adults who have thrombocytopenia low levels of platelets in the. For many years, argatroban has been used in japan and in the united states and is approved by the fda for anticoagulation in patients with heparininduced thrombocytopenia hit type ii. By continuing to browse this site you are agreeing to our use of cookies. Argatroban is a a small molecule, synthetic direct thrombin inhibitor. No dosage adjustment is necessary in patients with renal dysfunction.
Argatroban anticoagulation in intensive care patients. Clinical management of argatroban in patients with heparin. Argatroban is predominantly metabolized in the liver. Argatroban 125 mg in 125 ml aqueous sodium chloride solution 1 mgml is intended for administration to adult patients discontinue all parenteral anticoagulants before administering argatroban injection adjust dosing in patients with hit who have moderate or severe hepatic impairment heparininduced thrombocytopenia.
The aim of this study was to collect data in france in patients with heparininduced thrombocytopenia who required parenteral anticoagulation and for whom other nonheparin anticoagulant therapies were contraindicated including patients with renal failure, crossreactivity to danaparoid or at high hemorrhagic risk. Exclusion criteria also included malfunction of cardiovascular and respiratory sys tem, hepatic dysfunction, and infectious disease. Its short elimination halflife of 3551 min and major route of hepatic metabolism 70% are important aspects in patients with renal failure. Continuous infusion of argatroban at the arterial site can achieve. Clinical management of argatroban in patients with heparin induced thrombocytopenia type ii the safety and scientific validity of this study is the. Use of argatroban for hemodialysis and continuous veno. To report a case of significant hepatic and renal failure with the use of argatroban in a patient with heparininduced thrombocytopenia hit requiring continuous venoveno hemodialysis cvvhd. Heparin is one of the most frequently prescribed medications, with 12 million patients receiving heparin annually in the united states for thromboprophylaxis or treatment in a variety of clinical settings. Pdf argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparininduced thrombocytopenia hit find, read and cite. Therefore, in patients with renal failure, careful attention should be paid to the onset of bleeding tendency due to overdose of argatroban. Argatroban is a synthetic monovalent direct thrombin inhibitor, the molecular structure of which contains an arginine residue. Pdf argatroban and renal replacement therapy in patients with.
Argatroban is considered to be an alternative anticoagulant of choice in patients with heparininduced thrombocytopenia hit and renal impairment. Argatroban is a white, odorless crystalline powder that is freely soluble in glacial acetic acid, slightly soluble in ethanol, and insoluble in acetone, ethyl acetate, and ether argatroban injection is a sterile clear, colorless to pale yellow, slightly viscous solution in a singleuse amber vial containing 250 mg2. Argatroban anticoagulation in patients with heparin. Argatroban for heparininduced thrombocytopenia in hepato. Argatroban met all the requirements for the ideal anticoagulant in this case and. Efficacy of argatroban in critically ill patients with. Argatroban has specific molecular properties that allow this agent to have less risk of systemic anticoagulant effects.
Chronic renal failure was also identified by the receipt of hemodialysis within 4 days of. Background we prospectively evaluated 3 treatment regimens of argatroban, a direct thrombin inhibitor, for providing adequate, safe anticoagulation in patients with endstage renal disease esrd during hemodialysis. Pharmacokineticspharmacodynamics of argatroban injection. Argatroban argatroban for injection product monograph page 9 of 30 tachycardia ventricular 4 5 4 acute renal failure 3 5 7 nausea 3 6 2 pneumonia 2 5 15 respiratory insufficiency 1 6 0 cardiac failure 0 5 0 adverse events resulting from repeated or chronic administration. High risk of bleeding coagulopathy severe liver disease severe kidney disease adjusting argatroban dose based on aptt. It is a small molecule with a shorter halflife compared with lepirudin or fondaparinux and has selective reversible binding to the thrombin catalytic site hursting et al. Argatroban, a direct thrombin inhibitor, was evaluated for anticoagulation in continuous renal replacement therapy crrt in critically ill patients with. In a recent case series of critically ill hit patients with liver dysfunc tion and acute renal failure requiring continuous renal replacement therapy, the steadystate argatroban dose associated. Heparininduced thrombocytopenia in haemodialysis treated with. A prospective comparison of three argatroban treatment regimens during hemodialysis in endstage renal disease. Argatroban, a direct thrombin inhibitor, was evaluated for anticoagulation in continuous renal replacement therapy crrt in critically ill patients with heparininduced thrombocytopenia type ii and acute renal failure. Argatroban was able to provide effective anticoagulation without crossreacting with heparindependent antibodies, offered a relatively predictable doseresponse, proved to be easily monitored, and did not require dose adjustment for renal disease.
It is widely believed that no dosage adjustment is required in patients with renal insuf. Heparininduced thrombocytopenia and hemodialysis longdom. Argatroban anticoagulation in renal dysfunction karger publishers. Renal failure requiring renal replacement therapy rrt is a frequent complication in patients in whom hit develops after cardiovascular surgery. Haemodialysis had little or no effect on clearance. Lepirudin, which is renally excreted, requires dose adjustments in patients with renal insufficiency and should be avoided in patients with acute renal failure or those undergoing hemodialysis. Argatrobanrenal dysfunctionrenal replacement therapydialysis heparininduced thrombocytopeniaantithrombin deficiency. Argatroban dosing in intensive care patients with acute. Argatroban is a direct thrombin inhibitor approved for the treatment of heparininduced thrombocytopenia hit type ii. The investigation focused on predictors for the maintenance doses of argatroban with ef. Argatroban side effects, dosage, interactions drugs. The discontinuation of heparin and administration of argatroban resolved inefficiency of dialysis resulting from repeated coagulation of the circuit and catheter. Argatroban is capable of inhibiting the action of both free and clotassociated thrombin.
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