The use of heparin in patients with heparin-induced thrombocytopenia (HIT) may result in severe complications or death. The diagnosis of HIT is frequently uncertain, however. Alternative anticoagulants in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass remain problematic. The novel short-acting, direct-thrombin inhibitor bivalirudin is the only alternative to heparin/protamine being used in elective non-HIT patients during CPB.
Four patients with severe thrombocytopenia after heparin exposure and suspected acute HIT underwent on-pump coronary artery bypass grafting surgery with preemptive use of bivalirudin. A continuous bivalirudin infusion was used during cardiopulmonary bypass, and activated clotting times were used to monitor anticoagulation.
Anticoagulation with bivalirudin during cardiopulmonary bypass was effective and uncomplicated. Duration of operation was not prolonged, and perioperative blood loss and transfusion rates were acceptable. Activated clotting times were helpful for monitoring anticoagulation in these patients.
These data provide further evidence of the feasibility of bivalirudin for anticoagulation during on-pump coronary artery bypass graft surgery in urgent clinical situations.
"Pharmacokinetically bivalirudin is predominantly eliminated by enzymatic degradation through proteases and thrombin itself (80%) and to a lesser degree by renal clearance (20%) . No reversal for bivalirudin exists, but its elimination can be enhanced by hemodialysis and hemofiltration [81,82]. The theoretical potential of aprotinin to delay bivalirudin elimination and to prolong its anticoagulant effect has not been demonstrated . "
[Show abstract][Hide abstract] ABSTRACT: Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary.
Journal of Cardiothoracic Surgery 11/2010; 5(1, article 101):101. DOI:10.1186/1749-8090-5-101 · 1.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Summary Heparin-induced thrombocytopenia (HIT), next to bleeding complications, is the most important side-effect of heparin therapy in cardiac patients and the most frequently found thrombocytopenia induced by medication. Two types of HIT are distinguished on the basis of both severity of disease, and pathophysiology: type I HIT is an early, transient, clinically harmless form of thrombocytopenia, due to direct heparin-induced platelet aggregation. Thromboembolic complications are usually not seen. No treatment is required. A normalization of platelet count even if heparin is continued is a usual observation. Type II HIT is more severe than type I HIT and is frequently complicated by extension of preexisting venous thromboembolism or new arterial thrombosis. The thrombocytopenia is caused by a pathogenic heparin-dependent IgG antibody (HIT-IgG) that recognizes as its target antigen a complex consisting of heparin and platelet factor IV. Type II HIT should be suspected when the platelet count falls to less than 100,000 per cubic millimeter or less than 50% of the base line value 5 to 15 days after heparin therapy is begun, or sooner in a patient who received heparin in the recent past. The clinical diagnosis of type II HIT can be confirmed by several sensitive assays. In cases of type II HIT, heparin must be stopped immediately. However, if the patient requires continued anticoagulant therapy for an acute event such as deep venous thrombosis, substitution of an alternative rapid-acting anticoagulant drug is often needed. In the authors experience Danaparoid sodium, a low-sulfated heparinoid with a low cross-reactivity (10%) to heparin, can be regarded as an effective anticoagulant in patients with type II HIT. Preliminary experiences with intravenous recombinant hirudin are also encouraging and suggest that this direct thrombin inhibitor will emerge as a valuable alternative treatment for patients who suffer from HIT.
Seminars in Thrombosis and Hemostasis 02/1986; 12(1):59-62. DOI:10.1055/s-2007-1003534 · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bivalirudin (Hirulog, Angiomax) is a specific, reversible and direct thrombin inhibitor with a predictable anticoagulant effect. It is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration. Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly by binding to thrombin catalytic site and anion-binding exosite I in a concentration-dependent manner. Bivalirudin prolongs activated partial thromboplastin time, prothrombin time, thrombin time and activated clotting time (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy. Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective contemporary percutaneous coronary intervention (PCI). In respect to combined ischemic and hemorrhagic endpoints of death, myocardial infarction, unplanned urgent revascularization and major bleeding during PCI (including subgroups of patients with renal impairment and diabetes) bivalirudin is not inferior to unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin has been consistently shown to have significantly less in-hospital major bleeding than heparin alone or heparin in combination with a GpIIb/IIIa inhibitor. Bivalirudin appears to be also safe and effective during PCI in patients with heparin-induced thrombocytopenia. Finally, data from PCI studies support the safety and efficacy of bivalirudin, although its direct randomized comparison with unfractionated heparin is lacking.
Cardiovascular Drug Reviews 02/2005; 23(4):345-60. DOI:10.1111/j.1527-3466.2005.tb00177.x · 5.21 Impact Factor
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