Argatroban as a substitute of heparin during cardiopulmonary. Guidelines for the use of argatroban in hit anticoagulation. Use of argatroban for anticoagulation during cardiopulmonary. Acova argatroban dosing, indications, interactions. Argatroban as an alternative to heparin for vascular and cardiovascular surgery in.
The fda approved argatroban in june 2000 for treatment of thrombosis in patients with heparininduced thrombocytopenia hit, and for use in percutaneous coronary intervention pci in patients with hit. Fifteen patients underwent offpumpsurgical procedures with the argatroban dose adjusted to maintain an activatedclotting time act range between 200 and 300 s. Argatroban for anticoagulation during cardiopulmonary. The convenience of using the act and hitt to monitor the anticoagulation effect of argatroban was a significant advantage, as was the fact that its clearance is predominantly through the. Heparin is generally needed as an anticoagulant for cardiopulmonary bypass cpb in openheart surgery. It has a relatively short half life of 4050 minutes and is eliminated by hepatic metabolism and biliary secretion. When hit is diagnosed or suspected, heparins should be discontinued, and an alternative, fastacting, parenteral, nonheparin anticoagulation such as argatroban should be initiated. Argatroban therapy in heparininduced thrombocytopenia. It is used as an alternative anticoagulant in patients with heparininduced thrombocytopenia hit. Monitoring of anticoagulation with bivalirudin is more challenging. Two hours after the start of the argatroban infusion, an aptt level was obtained and dose adjustments were made to achieve a steadystate aptt value that was 1. Argatroban for an alternative anticoagulant in hit during ecmo.
Limited and inconsistent data exist about dosing of argatroban in intensive care. Pharmacokinetic and pharmacodynamic basis for effective. Argatroban anticoagulation for renal replacement therapy. This compound, previously known as hirulog, is a semisynthetic. The estimated clearance of argatroban in pediatric patients was 2. Anticoagulation during cardiopulmonary bypass society of. Reduced argatroban doses after coronary artery bypass graft. Priming dose of bivalirudin 50 mg in cpb circuit, bivalirudin, 11. The search terms combinations of argatroban and cardiovascular procedures and cardiopulmonary bypass were used. Sep 05, 2019 argatroban injection must be diluted 100fold prior to infusion. At therapeutic concentrations, argatroban has little or no effect on related serine proteases trypsin, factor xa, plasmin, and kallikrein. Argatroban side effects, dosage, interactions drugs. Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia hit or hit suspect is typically monitored using the activated partial thromboplastin time aptt.
Aug 30, 2019 in this case, in order to predict the inr on warfarin alone, temporarily reduce the dose of argatroban to a dose of 2 mcgkgmin. Cardiopulmonary bypass with bivalirudin in type ii heparin. The results of a retrospective analysis indicate that actual body weightadjusted argatroban dosing is safe and effective in obese patients and that adjustment of the initial dose is unnecessary in obesity. 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. Argatroban is a synthetic direct thrombin inhibitor and the chemical name is 15aminoiminomethylamino1oxo21,2,3,4tetrahydro3methyl8quinolinylsulfonylaminopentyl4methyl2piperidinecarboxylic acid, monohydrate. Argatroban as an alternative to heparin for vascular and. During cpb, the dose of argatroban was adjusted to maintain the activated. Body weight was significant predictor of argatroban clearance. Initial bivalirudin dosing was similar to the previous case, but in an attempt to shorten the recovery period, a lower target act of 400 to 500. There are a few reported cases in the literature of its use as an anticoagulant in patients with hit undergoing cardiopulmonary bypass for cardiac surgery.
Overall and within each group, the most frequent indications for heparin included coronary artery bypass graft surgery 16 argatroban treated patients, 11 control patients, unspecified surgery 12 argatroban treated patients, 7 control patients, and line or filter patency 17 argatroban treated patients, 5 control patients. Argatroban 125 mg in 125 ml aqueous sodium chloride solution 1 mgml is intended for administration to adult patients 2. Anticoagulation during cardiopulmonary bypass amsect. Worrall, md the heart institute of spokane, spokane, washington whereas heparin is the most widely used intravenous. Cardiopulmonary bypass using argatroban as an anticoagulant. The molecular formula of argatroban is c 23 h 36 n 6 o 5 sh 2 o. Argatroban as a substitute of heparin during cardiopulmonary bypass. We report a case where the challenges in dosing argatroban led to failure to provide adequate anticoagulation during cpb, as evidenced by clot formation in the oxygenator, and extensive bleeding in the postoperative period.
Monitoring of argatroban and lepirudin anticoagulation in. Bivalirudin angiomax, a direct thrombin inhibitor, has been recently used with success as an antithrombotic agent during the treatment of acute coronary syndromes 2, 3. Use of bivalirudin as an anticoagulant during cardiopulmonary. Argatroban injection should not be mixed with other drugs prior to dilution. The use of argatroban for cardiopulmonary bypass remains off label and the subject of a few case reports. In this case, argatroban was titrated to achieve a target aptt of 60 to 100s, and act was maintained for 400s or more during cardio pulmonary bypass as in the normal heart surgery. Use of argatroban in combination with nafamostat mesilate in. The initial dose of argatroban was 2 mcgkgmin, not to exceed 10 mcgkgmin.
Argatroban suggested guidelines for use university of. Administration of heparin to patients with heparininduced thrombocytopenia hit type ii can result in thromboembolic events, severe bleeding, and death. Simulations were performed to derive a dosing regimen for pediatric patients. Pdf bivalirudin is a shortacting direct thrombin inhibitor that has been used in. In addition, the relationship between the varying doses of argatroban and act values was studied by analyzing a set of data collected from our experience. Surgeons retrieved a 2mm clot from the left pulmonary artery and replaced the bt shunt.
Acova argatroban dosing, indications, interactions, adverse. No bleeding events attributed to problems of anticoagulation were observed. Challenges encountered with argatroban anticoagulation during cardiopulmonary bypass article pdf available in journal of anaesthesiology clinical pharmacology 281. The use of argatroban as an anticoagulant for cardiopulmonary. Indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparininduced thrombocytopenia. The recommended initial dose of argatroban for adult patients without hepatic impairment is 2 mcgkgmin, administered as a continuous infusion see table 1.
Three intraoperative thrombioccurred in two patients when the act was dose of argatroban has to be reduced to 0. Alcoholinduced dilated cardio myopathy decompensated by subsegmental pulmonary embolism was the final clinical diagnosis. Although aptt correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. Dec 17, 2018 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. To characterize dosing requirements, aptts, factors affecting dosage, and clinical outcomes in patients administered argatroban after coronary artery bypass graft cabg surgery. Its use as an anticoagulant for cardiopulmonary bypass remains offlabel. Standard argatroban infusion is 250mg in normal saline 250ml, yielding a concentration of 1 mgml or mcgml. The development of cardiopulmonary bypass cpb in the 1960s so. Before administering argatroban, discontinue heparin therapy and obtain a baseline aptt.
Argatroban anticoagulation for cardiac surgery with cardiopulmonary bypass in an infant with double outlet right ventricle and a history of heparininduced thrombocytopenia congenit heart dis 2008. This case exemplifies the successful use of argatroban for anticoagulation during emergent cardiac surgery where heparin was contraindicated. Argatroban and bivalirudin for perioperative anticoagulation in. May 25, 2017 argatroban 125 mg in 125 ml aqueous sodium chloride solution 1 mgml is intended for administration to adult patients 2. Repeat the inr on argatroban and warfarin 4 to 6 hours after reduction of the argatroban dose and follow the process outlined above for administering argatroban at doses up to 2 mcgkgmin. Successful use of argatroban as a heparin substitute during. The aim of this retrospective study was to evaluate the safety of argatroban dosage in critically ill patients, operationalized as number of thromboembolic events i. Note that argatroban is a nonformulary drug at uw medicine. Argatroban in sodium chloride injection is a sterile, nonpyrogenic, clear, colorless to pale yellow solution. The anticoagulant effect of heparin is dependent on the level of antithrombin iii at iii. Argatroban injection is a sterile clear, colorless to pale yellow, slightly viscous solution in a singleuse amber vial containing 250 mg2. Heparininduced thrombocytopenia in a highrisk cardiac surgical patient jeff t. Results of a consensus meeting on the use of argatroban in patients.
Successful use of argatroban as a heparin substitute during cardiopulmonary bypass. Because of the strong correlation between argatroban dosing require. Bleeding rates were lower, but not significantly, in patients receiving argatroban 10% for heparin vs. Reduced argatroban doses after coronary artery bypass. 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 for anticoagulation in continuous renal. We report the case of a patient with a heparin allergy requiring cardiopulmonary bypass. Particularly in critical patients with impaired liver function, the elimination. Anticoagulation, argatroban, cardiopulmonary bypass, heparin induced. Heparin is the most common agent used, but in selective circumstances, alternate form of anticoagulation may be considered. Argatroban dosing nomogram hold argatroban for min. Argatroban is capable of inhibiting the action of both free and clotassociated thrombin. Argatroban is highly selective for thrombin with an inhibitory constant k. Argatroban is a a small molecule, synthetic direct thrombin inhibitor.
Data for argatroban dosing and aptt values are presented in table 1. Argatroban therapy for heparininduced thrombocytopenia in. Follis f, filippone g, montalbano g, floriano m, lobianco e, dancona g et al. Cardiopulmonary bypass using argatroban as an anticoagulant for a 6. Anticoagulation with bivalirudin during cardiopulmonary. The argatroban infusion rate and resultant acts during the case are shown in figure 1. However, our patient suffered a venous thrombosis in the early postoperative period. Heparininduced thrombocytopenia hit is a serious, prothrombotic, immunemediated adverse reaction triggered by heparin therapy. Argatroban fda prescribing information, side effects and uses. Safety and economic considerations of argatroban use in. Challenges encountered with argatroban anticoagulation. Fourteen dogs were divided into 3 groups in which partial venoarterial bypass was carried out. While the case report and teg data were interesting, based on our experience at virginia commonwealth university health system, we believe that bivalirudin angiomax.
Successful use of argatroban as a heparin substitute. One of the asymmetric carbons has an r configuration. Dosing of argatroban during cpb is complex due to lack of complete. Challenges encountered with argatroban anticoagulation during. Request pdf argatroban for anticoagulation during cardiopulmonary bypass in an infant heparin induced thrombocytopenia hit is a rare, but potentially lifethreatening complication of heparin. Anticoagulation, argatroban, cardio pulmonary bypass, heparin induced thrombocytopenia, heparin alternative. Argatroban therapy in heparininduced thrombocytopenia with. Heparinless cardiopulmonary bypass with argatroban in dogs. Nov 01, 2018 argatroban consists of a mixture of r and s stereoisomers at a ratio of approximately 65. Argatroban, a direct thrombin inhibitor that binds avidly and reversibly to the catalytic site of thrombin. The argatroban infusion was turned off 69 minutes before the termination of. Bivalirudin for cardiopulmonary bypass in the setting of.
Use of argatroban as an alternative to heparin during cardiopulmonary bypass cpb in patients with heparininduced thrombocytopenia has gained some attention in the past two decades. Argatroban side effects, dosage, interactions drugs everyday health search. The act monitoring was adequate and there were no unexpected complications. However, the use of heparin may cause problems in patients with a reduced antithrombin iii atiii level or with protamine allergy. Heparin induced thrombocytopenia adult inpatient clinical.
Argatroban for anticoagulation during cardiopulmonary bypass. Dosing recommendation for cardiopulmonary bypass cpb. Argatroban, a direct thrombin inhibitor that binds. Argatroban is an anticoagulant thrombin inhibitor that helps prevent the formation of blood clots. The use of argatroban as an anticoagulant for cardiopulmonary bypass in cardiac.
Use of argatroban in combination with nafamostat mesilate. Argatroban, a selective and competitive antithrombin agent synthesized in japan, was assessed for use as an alternative anticoagulant for partial venoarterial bypass with an oxygenator, by determining serial changes in hemostatic molecular markers. After argatroban is discontinued, a repeat inr should be obtained 4 to 6 hours after stopping the infusion. Overall and within each group, the most frequent indications for heparin included coronary artery bypass graft surgery 16 argatrobantreated patients, 11 control patients, unspecified surgery 12 argatrobantreated patients, 7 control patients, and line or filter patency 17 argatrobantreated patients, 5. Argatroban for offpump coronary artery bypass surgery. Guidelines for using bivalirudin during cardiopulmonary. Argatroban as an alternative to heparin for vascular and cardiovascular surgery in patients with a history of hit. Bivalirudin for cardiopulmonary bypass in the setting of heparin. Pdf challenges encountered with argatroban anticoagulation. The argatroban infusion was turned off 69 minutes before the termination of bypass because of elevated acts. Argatroban is not for use in patients with moderate to severe hepatic insufficiency. Management and monitoring of anticoagulation at the beginning of crrt, all patients received argatroban at a dose of 100 gkg as a bolus injection followed by a continuous infusion of 1 gkgmin.
It is not a substitute for appropriate clinical evaluation and does not supersede clinical judgment. Mejak b, giacomuzzi c, shen i, boshkov l, ungerleider r. Dosing of argatroban during cpb is complex due to lack of complete understanding of its pharmacokinetic profile and the various elements during cpb that may alter. Argatroban anticoagulation for renal replacement therapy in. Despite the pharmacological treatment optimization, the patient remained in poor clinical and haemodynamic conditions leading to right femoralfemoral venoarterial ecmo implementation on day 2.
Adult argatroban drip protocol this protocol reflects current evidence based clinical practice. Mitsubishi tokyo chemical corporation, tokyo, japan is a unique synthetic direct thrombin inhibitor developed in japan. Uptodate, electronic clinical resource tool for physicians and patients that provides information on adult primary care and internal medicine, allergy and immunology, cardiovascular medicine, emergency medicine, endocrinology and diabetes, family medicine, gastroenterology and hepatology, hematology, infectious diseases, nephrology and. Concomitant use of argatroban with antiplatelet agents, thrombolytics, and other anticoagulants may increase the risk of. Argatroban for anticoagulation during cardiac surgery. Guidelines for using bivalirudin during cardiopulmonary bypass surgery during cardiopulmonary bypass procedures, systemic anticoagulation to prevent thrombosis in the patient as well as the circuit is utilized. Standard infusion rate change after starting at 2mcgkgmin 2.
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