Anticoagulation with bivalirudin during cardiopulmonary bypass in cardiac surgery

Heparin is the standard agent used for systemic anticoagulation during cardiopulmonary bypass in cardiac operations. Alternatives are needed when patients with heparin-induced thrombocytopenia type II are encountered. We present a patient with a clinical picture of heparin-induced thrombocytopenia type II who was effectively anticoagulated with bivalirudin, a direct thrombin inhibitor, during cardiopulmonary bypass for a cardiac operation.     

An assay to monitor bivalirudin levels on cardiopulmonary bypass

Anticoagulation therapy for cardiopulmonary bypass in patients with recently diagnosed heparin-induced thrombocytopenia can be particularly challenging. Although heparin is the standard of care, in these situations anticoagulation is achieved with alternative agents such as direct thrombin inhibitors. Therapeutic concentrations are difficult to assess with direct thrombin inhibitors, and their use is riddled with bleeding and thrombotic complications. We report the successful use of a specific chromogenic antifactor IIa assay in a patient with heparin-induced thrombocytopenia who received anticoagulation therapy with bivalirudin during cardiopulmonary bypass for coronary artery bypass graft surgery.     

Bivalirudin anticoagulation for a patient with hypercoagulable immune syndromes undergoing mitral valve surgery

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.     

Update in hematology: heparin-induced thrombocytopenia and bivalirudin

Heparin-induced thrombocytopenia (HIT) is important because it is common, and it significantly increases mortality after cardiac surgery. Although thrombocytopenia after cardiac surgery is common, it predicts serious adverse outcome when it is severe. Despite the high prevalence of heparin/platelet factor 4 antibodies in cardiac surgical patients, they typically do not indicate a higher perioperative risk. Recent evidence suggests, however, that when these antibodies are in the immunoglobulin M class, there is an increased risk of nonthrombotic adverse outcomes after cardiac surgery. According to the guidelines from the American College of Chest Physicians, patients with HIT require parenteral anticoagulation with a direct thrombin inhibitor such as lepirudin, argatroban, or bivalirudin. The transition to oral anticoagulation must be undertaken cautiously and only after the platelet count has recovered. Patients with a remote history of HIT can have cardiac surgery safely with unfractionated heparin. Patients with clinically active HIT who require cardiac surgery before the resolution of the HIT preferably should be anticoagulated with bivalirudin, dosed according to body weight and the goal-activated coagulation time. Given that bivalirudin is an established alternative to heparin as a thrombin inhibitor for cardiac surgery, it is likely that future trials will investigate which anticoagulant confers better outcomes after cardiac surgery, as is the case in percutaneous coronary intervention.     

Delayed thrombin generation with hirudin anticoagulation during prolonged cardiopulmonary bypass

Patients with heparin-induced thrombocytopenia requiring urgent cardiac surgery present a unique challenge that must be addressed by the use of nonheparin alternatives for anticoagulation during cardiopulmonary bypass. Although isolated cases have been presented involving the use of antithrombin III independent thrombin inhibitor hirudin in this situation, its ability to completely inhibit thrombin activity has not been demonstrated. In this report we describe the efficacy of this drug in inhibiting thrombin during a case requiring prolonged cardiopulmonary bypass.     

Bivalirudin utilization in cardiac surgery: shifting anticoagulation from indirect to direct thrombin inhibition

Purpose

Bivalirudin use for anticoagulating patients undergoing cardiac surgery, particularly those with or at risk for heparin-induced thrombocytopenia, has expanded over the past several years. The purpose of this review is to provide a summary of the following: the differences between indirect and direct thrombin inhibition, unfractionated heparin’s limitations (i.e., heparin-induced thrombocytopenia), bivalirudin’s pharmacology, recent cardiac surgery trials comparing bivalirudin and unfractionated heparin as anticoagulants, the growing role of bivalirudin-mediated anticoagulation for various surgical procedures, and the potential of bivalirudin-mediated vascular graft patency.

Source

A systematic search of the English literature was performed using PubMed from the United States National Library of Medicine. Pertinent articles from 1992-2010 were obtained from this search, and their reference lists were used to retrieve additional relevant articles.

Principal findings

In small studies in the cardiac surgery arena, bivalirudin has demonstrated a similar safety and efficacy profile compared with unfractionated heparin. Bivalirudin’s role as an anticoagulant in various cardiac surgical procedures (i.e., heart transplant) and vascular surgical procedures is growing and reviewed. Additionally, the molecular basis for the potential for bivalirudin-mediated improvement in vascular graft patency after coronary artery bypass graft procedures is discussed.

Conclusion

Although bivalirudin is not approved for cardiac surgery in the United States, it can be used in this setting in Canada as an anticoagulant in patients with heparin-induced thrombocytopenia provided the cardiac anesthesiologist is knowledgeable about potential complications from its use and knows how to manage or mitigate their incidence appropriately. During cardiopulmonary bypass, bivalirudin anticoagulation protocols must be thoroughly followed to attain optimal clinical outcomes. Additionally, further studies with bivalirudin are needed to determine the best monitoring modality and dosing regimen.     

Bivalirudin anticoagulation for cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia

PURPOSE: To describe the perioperative management in a heparin-induced thrombocytopenia (HIT) positive patient who had prosthetic valve endocarditis and an aortic root abscess. The patient underwent high-risk cardiac re-operation with the use of the alternative anticoagulant, bivalirudin. CLINICAL FEATURES: A 62-yr-old patient who underwent stentless tissue aortic valve replacement with a Toronto-SPV valve in 1998, was admitted to hospital with symptoms of stroke. A heparin infusion was started and further investigation revealed positive blood cultures. The patient developed HIT which was confirmed by laboratory tests. Echocardiographic examination performed one month later showed vegetations on the aortic tissue valve and a small aortic root abscess. The patient still tested positively for the presence of HIT antibodies and was treated conservatively with antibiotics. A repeat echocardiographic examination showed progression of the aortic root abscess and it was decided to proceed with urgent redo aortic valve surgery. Anticoagulation for cardiopulmonary bypass (CPB) was achieved with the use of a direct thrombin inhibitor (DTI), bivalirudin. Following an uneventful wean from CPB, hemostasis was achieved within 40 min. The postoperative course was uncomplicated and the patient was discharged from hospital on the seventh postoperative day. CONCLUSION: Bivalirudin is a DTI, which can be used as an alternative anticoagulant for CPB in HIT positive patients. This case report showed a favourable outcome with bivalirudin for urgent complex redo cardiac surgery requiring CPB.     

Deep hypothermic circulatory arrest and bivalirudin use in a patient with heparin-induced thrombocytopenia and antiphospholipid syndrome

BACKGROUND: Patients with heparin-induced thrombocytopenia II (HIT II) need an alternative nonheparin-based method of anticoagulation for cardiopulmonary bypass (CPB) to prevent thrombosis and thrombosis related complications. METHODS: Bivalirudin was used during CPB and deep hypothermic circulatory arrest (DHCA) for resection of multiple right atrial masses in a patient with HIT II and antiphospholipid antibodies syndrome (APS). Anticoagulation was monitored with the activated clotting time (ACT) and a target ACT of 450 seconds or greater was maintained. RESULTS: Surgical removal of multiple right atrial masses was successful and there was no evidence of thromboembolic events. Clot was noticed in the cardiotomy and venous reservoir after CPB was discontinued and the system flushed. The postoperative course was uneventful. CONCLUSIONS: Anticoagulation was successfully managed with bivalirudin, a new short-acting, and direct thrombin inhibitor. Further studies are necessary to evaluate the safety of bivalirudin during DHCA.     

Management strategies for heparin-induced thrombocytopenia in heart-transplant candidates: case report and review of the literature.

Management of anticoagulation in patients with heparin-induced thrombocytopenia (HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac transplantation, represents a difficult clinical problem and no clear management strategy exists. The cases of 2 patients with HIT who underwent cardiac transplantation using differing anticoagulation strategies are presented with a discussion of potential advantages and pitfalls of each approach used.     

Argatroban for anticoagulation during cardiopulmonary bypass in an infant

Heparin induced thrombocytopenia (HIT) is a rare, but potentially life-threatening complication of heparin therapy. In patients with HIT, alternative means of anticoagulation are necessary. The authors present an infant with HIT who required anticoagulation during cardiopulmonary bypass for tricuspid valve excision in the treatment of bacterial endocarditis. The direct thrombin inhibitor, argatroban, was successfully used. Previous reports regarding the use of argatroban and other nonheparin anticoagulants for anticoagulation are reviewed and suggestions regarding argatroban dosing in infants are presented.     

Anticoagulant monitoring techniques in a heparin-induced thrombocytopenia patient undergoing cardiopulmonary bypass using bivalirudin anticoagulant

Heparin is widely used as the anticoagulant of choice for cardiopulmonary bypass. However, some patients exposed to heparin therapies develop heparin-induced thrombocytopenia (HIT). Severe complications of HIT-induced thrombosis may lead to end-organ dysfunction and death. Bivalirudin, a hirudin analog, is an alternative anticoagulant that may be used in the patient with HIT without inducing thrombotic disorders. This case report provides a look at the successful use of bivalirudin as the sole anticoagulant in a patient diagnosed with HIT undergoing minimally invasive cardiothoracic surgery requiring cardiopulmonary bypass for severe mitral insufficiency. An 80-year-old male presented to the operating room for a minimally invasive mitral valve repair. Past medical history included mitral valve prolapse, atrial fibrillation, hypertension, and congestive heart failure. Preoperative evaluation noted the existence of HIT with heparin exposure 2 months prior. The decision was made to use bivalirudin as the sole anticoagulant for the operative procedure. Anticoagulation evaluation was performed with both high-does thrombin time (HiTT) and Celite activated clotting time tubes for comparison using a Hemochron device. Cardiopulmonary bypass was initiated, and the patient's mitral valve was repaired using a 34-mm annuloplasty ring. The patient was successfully weaned from bypass. No complications or evidence of HIT exacerbation were noted in the postoperative course.     

Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia

Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.     

Anticoagulation management and cardiac surgery in patients with heparin-induced thrombocytopenia

Unfractionated heparin (UFH) is the gold standard for anticoagulation during cardiopulmonary bypass (CPB). Of patients undergoing CPB operations, 25% to 50% develop heparin-dependent antibodies during the postoperative period, typically between day 5 and 10, if UFH is continued during the postoperative course. In 1% to 3% of all patients undergoing CPB operation with UFH anticoagulation, these antibodies activate platelets causing a prothrombotic disorder, known as heparin-induced thrombocytopenia (HIT), which can lead to life-threatening thromboembolic complications. If urgent cardiac operation with the use of CPB in patients with positive antibody titer is required, different anticoagulatory approaches are available, such as lepirudin, bivalirudin, and danaparoid or UFH in combination with platelet antagonists, such as epoprostenol or tirofiban. In patients with previous HIT but no detectable antibodies, UFH alone can be used only during CPB, but alternative anticoagulation has to be used pre- and postoperatively.     

Successful use of Argatroban as a heparin substitute during cardiopulmonary bypass: heparin-induced thrombocytopenia in a high-risk cardiac surgical patient

Whereas heparin is the most widely used intravenous anticoagulant in the US for the treatment of thromboembolic disease and is a seminal adjunct to many clinical procedures, its use can cause serious adverse events. Heparin-induced thrombocytopenia (HIT) has emerged as one of the most frequently seen complications of heparin therapy and can be a life-threatening immunohematological challenge for patients requiring cardiopulmonary bypass (CPB) with obligatory heparin exposure. Unfortunately, lack of convenient monitoring techniques and the presence of HIT and other comorbidities in the complex patient frequently limits or precludes the use of most alternatives to heparin anticoagulation during CPB. This case report describes the successful use of the celite activated clotting time and high-dose thrombin time, while using the direct thrombin inhibitor Argatroban as an alternative to heparin anticoagulation during CPB in a high-risk patient presenting with type II HIT, end-stage renal failure, and ischemic cardiomyopathy with ventricular fibrillatory arrest.     

Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced thrombocytopenia and cardiopulmonary bypass

Heparin-induced thrombocytopenia (HIT) is described as an allergy-like adverse reaction to heparin. It is a potentially severe complication of heparin therapy that can result in serious or life-threatening venous or arterial thromboembolic events. In the United States, lepirudin (Aventis Pharma AG, Strasbourg, France) is an approved therapy for anticoagulation in patients with HIT requiring anticoagulation. Lepirudin is a recombinant form of hirudin, a leech enzyme that is a highly specific direct inhibitor of thrombin. Lepirudin monitoring during surgery can be managed with ecarin clotting time (ECT) (Cardiovascular Diagnostics, Inc., Raleigh, NC), which has recently been approved as a humanitarian device exemption (HDE) for use in the United States in the management of HIT with cardiopulmonary bypass. This case report describes a patient with HIT who was managed successfully with lepirudin and ECT during coronary artery bypass grafting.     

Cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia II and impaired renal function using heparin and the platelet GP IIb/IIIa inhibitor tirofiban as anticoagulant

In a patient with heparin-induced thrombocytopenia II and impaired renal function, anticoagulation during cardiopulmonary bypass was successfully performed by the use of unfractionated heparin and the platelet glycoprotein IIb/IIIa inhibitor tirofiban. Postoperative antithrombotic therapy with recombinant hirudin was immediately initiated. This regimen for anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia II appears to be particularly appropriate for patients with impaired renal function or for hospitals without special experience with other alternative anticoagulation strategies.     

L’argatroban,nouvel antithrombotique pour la thrombopénie induite par l’héparine en chirurgie cardiaque de l’adulte : utilisation en chirurgie cardiaque et en réanimation

ObjectivesAlthough heparin-induced thrombocytopemia (HIT) is uncommon, its thromboembolic complications are potentially life-threatening. The low-molecular weight heparins are less responsible of HIT than unfractionated heparin (UFH) but this latter is still indicated in some circumstances such as cardiac surgery. Argatroban, a selective thrombin inhibitor, recently available, has been indicated in HIT treatment. This review presents the main pharmacological characteristics, its indications and uses in the context of cardiac surgery and in intensive care medicine.MethodsReview of the literature in Medline database over the past 15 years using the following keywords: argatroban, cardiac surgery, circulatory assistance, cardiopulmonary bypass.ResultsDespite its short-acting pharmacokinetic, argatroban cannot be recommended during cardiopulmonary bypass. On the contrary, argatroban is indicated in many circumstances in postoperative period of various cardiac surgeries (on-pump, off-pump, circulatory assistance). Nevertheless, after cardiac surgery, doses have to be adapted according to coagulation laboratory testing (ACT), particularly in patients presenting acute organ failure (kidney injury, heart failure, liver failure). This compound has no antagonist and is excluded during severe hepatic failure. The continuous intravenous administration is a drawback.ConclusionArgatroban is a new direct competitive thrombin inhibitor well evaluated as treatment of HIT after cardiac surgery. In HIT management, argatroban is an interesting alternative to lepirudin that is not anymore available and danaparoid because of supply disturbances.     

Anticoagulation for patients with heparin-induced thrombocytopenia using recombinant hirudin during cardiopulmonary bypass

Heparin-induced thrombocytopenia (HIT) is a common complication of heparin therapy. There are three types of HIT. In the majority of patients, thrombocytopenia is modest and resolves without sequelae (HIT I). In a smaller number of patients, the thrombocytopenia is severe (HIT II), and in still others, the thrombocytopenia is also associated with thrombosis (HITT). Administration of heparin to this latter group of patients causes platelet aggregation, thromboembolism, and thrombocytopenia. It is advisable that heparin not be administered in any form to patients with documented or suspected HIT II or HITT. This situation, of course, poses a problem for those patients requiring cardiopulmonary bypass (CPB) surgery. In this report, we summarize our experience with Lepirudin (Hoechst, Frankfurt Ammain, Germany), which is a recombinant hirudin (r-hirudin), as an alternative to heparin for systemic anticoagulation, as well as the use of the ecarine clotting time (ECT) for monitoring anticoagulation status during CPB.     

Cardiac surgery with cardiopulmonary bypass in patients with type II heparin-induced thrombocytopenia

BACKGROUND: The use of cardiopulmonary bypass (CPB) in patients with a history of type II heparin-induced thrombocytopenia (HIT) may be associated with complications related to their anticoagulation management. METHODS: Between January 1997 and December 1999, among 4,850 adults patients who underwent cardiac surgery in our institution, 10 patients presented with preoperative type II HIT. In 4 patients, anticoagulation during CPB was achieved with danaparoid sodium. In 6 other patients, heparin sodium was used after pretreatment with epoprostenol sodium. RESULTS: No significant change in platelet count occurred in any patient. No intraoperative thrombotic complication was encountered. Total postoperative chest drainage ranged from 250 to 1,100 ml in patients pretreated with epoprostenol and 1,700 to 2,470 ml in patients who received danaparoid sodium during CPB (p < 0.05, Mann-Whitney U test). CONCLUSIONS: During CPB, inhibition of platelet aggregation by prostacyclin may be a safe anticoagulation approach in patients with type II HIT.