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Bivalirudin for Prevention of Prosthetic Valve Thrombosis in Heparin Allergy n Palacios-Rubio, M.D., Leonel Cano, M.D., Isidre Vilacosta, M.D., Ph.D., F.E.S.C., Julia and David Vivas, M.D., Ph.D. Instituto Cardiovascular, Hospital Clı´nico San Carlos, C/Prof. Martı´n Lagos, s/n, Madrid, Spain ABSTRACT A 68-year-old male was admitted for implantation of an implantable cardioverter defibrillator (ICD). He had a prosthetic mechanical valve for which he was receiving anticoagulation with warfarin, but had developed an allergy to heparin. Therefore, we decided to use bivalirudin for anticoagulation, which permitted him to undergo the procedure without complications. doi: 10.1111/jocs.12186 (J Card Surg
In patients on oral anticoagulation therapy that require implantation of devices such as pacemakers, current guidelines recommend bridging to shorter action agents such as heparin.1 In patients with heparin allergy, hirudin agents may minimize both bleeding and thrombotic risks. PATIENT PROFILE A 68-year-old male with a prosthetic mechanical mitral valve (St. Jude Medical, nr. 29, mitral) was receiving oral anticoagulation with warfarin with a target international normalized ratio (INR) of 2.5 to 3.5. In 1997 he had a myocardial infarction, with subsequent ischemic episodes and heart failure that required percutaneous angioplasty, coronary bypass surgery, and mitral valve replacement. Thereafter, he experienced several transient ischemic attacks and strokes. During one of these hospital admissions he suffered an allergic reaction to heparin. The patient had a left ventricular ejection fraction of 15%, and bursts of ventricular tachycardia. Therefore, he was referred for implantation of an implantable cardioverter defibrillator (ICD). His high risk of thromboembolism mandated the use of short half-life drugs such as unfractionated heparin (UFH) or low-molecularweight heparins (LMWH). However, this was not possible due to his history of hypersensitivity to heparins including fondaparinux. Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Juli an Palacios-Rubio, M.D., Instituto Cardiovascular, Hospital Clı´nico San Carlos, C/Prof. Martı´n Lagos, s/n, Madrid, Spain. Fax: þ34 91 3303291; e-mail: [email protected]
Bivalirudin, a synthetic 20-amino acid analogue of hirudin, has a plasma half-life of 25 minutes, the shortest half-life of all the parenteral direct thrombin inhibitors. These features made it especially useful for this patient. Warfarin was last administered 39 hours prior to ICD implantation. Fifteen hours later (INR 2.3), an infusion of 0.75 mg/kg/hour of bivalirudin was started. Its activity was assessed using activated clotting time (ACT). ACT was measured with a portable microcoagulation system (Hemochron JR Signature Plus, ITC, Edison, NJ, USA) that reports ACT as CeliteTM-equivalent seconds. Three hours after starting bivalirudin, ACT was 394 seconds, and seven hours later ACT was 367 seconds. Since these values were similar to those reported in previous studies,2 and higher than the minimum 225 seconds indicated in the product information sheet, a dose adjustment was not performed and the infusion was continued. The following day, 22 hours after bivalirudin was started, the patient underwent the ICD implantation. Drug infusion was suspended 30 minutes before the procedure. The procedure was successful and 32 hours after implantation bivalirudin was restarted at a rate of 0.70 mg/kg/hour. This dosage achieved an ACT of 193 seconds one hour later, so the infusion rate was increased to 0.84 mg/kg/hour raising the ACT to 307 seconds. Oral anticoagulation was reintroduced the following afternoon. No significant side effects, other than mild dizziness, were reported by the patient. ACT values ranged between 192 and 352 seconds throughout this period. Three days after restarting warfarin, when the INR value was 3.2, bivalirudin was stopped and the patient was discharged.
J CARD SURG 2013;28:520–521
PALACIOS-RUBIO, ET AL. BIVALIRUDIN IN HEPARIN ALLERGY
DISCUSSION Unusual immediate-type allergic reactions to UFH and LMWH have been reported,3 as well as the more common delayed-type hypersensitivity.4 In such cases, fondaparinux has been used,5 but this patient had previously developed a pruriginous rash after use of this drug. Hirudins have been used with success in similar settings due to their different molecular structure that prevents cross-reactivity. An in vitro study assessing bivalirudin effectiveness to prevent mechanical valve thrombosis did not find differences in clot formation between UFH and bivalirudin infusion.2 The safe use of bivalirudin for cardiopulmonary bypass (CPB) in heart surgery has already been established.6 Some case reports of off-label use of bivalirudin during on-pump coronary artery bypass and valve replacement surgery prompted two clinical trials (CHOOSE-ON and EVOLUTION-ON) that showed the safety and feasability of bivalirudin use instead of heparin for the duration of CPB.7,8 Nevertheless, there is scarce literature about bivalirudin use in prosthetic valves in settings outside of CPB or for longer time periods. There is a case report about the use of bivalirudin as standalone anticoagulant for three days in a patient with an aortic mechanical valve suffering from heparin-induced thrombocytopenia9 but this regimen has not been previously reported for use in patients with mechanical mitral valves. REFERENCES 1. Douketis JD, Spyropoulos AC, Spencer FA, et al: Perioperative management of antithrombotic therapy: Antithrom-
botic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e326S– e350S. Maegdefessel L, Linde T, Michel T, et al: Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves. Results of an in vitro study. Thromb Haemost 2009;101:1163–1169. Warkentin TE, Greinacher A: Heparin-induced anaphylactic and anaphylactoid reactions: Two distinct but overlapping syndromes. Expert Opin Drug Saf 2009;8:129–144. Schindewolf M, Schwaner S, Wolter M, et al: Incidence and causes of heparin-induced skin lesions. CMAJ 2009;181:477–481. Schindewolf M, Scheuermann J, Kroll H, et al: Low allergenic potential with fondaparinux: Results of a prospective investigation. Mayo Clin Proc 2010;85:913– 919. Grubb KJ, Salehi P, Chedrawy EG: Bivalirudin: Alternative anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. Recent Pat Cardiovasc Drug Discov 2010;5:20–24. Koster A, Dyke CM, Aldea G, et al: Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: Results of the CHOOSE-ON trial. Ann Thorac Surg 2007;83:572–577. Dyke CM, Smedira NG, Koster A, et al: A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: The EVOLUTION-ON study. J Thorac Cardiovasc Surg. 2006;131:533–539. Klein M, Tomer A, Swartz A, et al: Bivalirudin for anticoagulation in mechanical aortic valve replacement and heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis 2006;17:331–333.