bivalirudin and Thrombophilia

Topics: Angina, Unstable; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Brain Ischemia; Clinical Trials as Topic; Coumarins; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Forecasting; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Morpholines; Myocardial Infarction; Peptide Fragments; Polysaccharides; Prothrombin; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Thrombosis; Warfarin

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications.. We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (P=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (P=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P=0.001).. In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Aspirin; Blood Coagulation Tests; Clopidogrel; Comorbidity; Coronary Restenosis; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Stents; Thrombophilia; Ticlopidine; Tirofiban; Tyrosine

Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Coronary Artery Bypass; Disseminated Intravascular Coagulation; Drug Substitution; Fatal Outcome; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Immunoglobulin G; Intraoperative Complications; Male; Multiple Organ Failure; Peptide Fragments; Platelet Factor 4; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombophilia

Bivalirudin is an ultrashort acting direct thrombin inhibitor, which has been used in place of heparin in selected settings. We describe our preliminary experience with the use of bivalirudin in patients who required anticoagulation for a deep vein thrombosis, prosthetic heart valve, or hypercoagulable state but were felt to be at high risk for the use of heparin.. Eight patients in our neurocritical care unit required anticoagulation but were felt to be poor candidates for heparin either due to heparin-induced thrombocytopenia or due to high risk for intracranial hemorrhage. A standard protocol was utilized for bivalirudin with a loading dose of 0.75 mg/kg followed by a continuous infusion of 0.15 mg/kg hr. Serial aPTT levels were checked on a routine basis to monitor therapeutic effect. The bivalirudin infusion was continued for a period of 2 days to 2 weeks prior to starting coumadin therapy.. These patients were in the early postoperative period (within 48 h) following craniotomy, had suffered a recent large hemispheric infarct with hemorrhagic conversion, or had presented with an acute intracerebral hemorrhage. In this small series of patients, no intracranial hemorrhagic complications were encountered. No patients demonstrated progressive systemic thrombotic issues while on bivalirudin.. Based on these findings, bivalirudin may represent a reasonable alternative in patients for whom heparin anticoagulation is contraindicated. A larger multicenter trial of bivalirudin in this setting may be appropriate.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Female; Heart Valve Prosthesis; Hirudins; Humans; Intracranial Hemorrhages; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thromboembolism; Thrombophilia; Treatment Outcome; Venous Thrombosis

Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative disorder with incidence of 1% under the age of 25. The Budd-Chiari syndrome (BCS) is a well known complication of polycythemia vera even in children, and characterized by occlusion of hepatic outflow. A computerized archive search of medical records at Sheba Medical Center of the past three decades of patients with polycythemia vera and BCS under the age of 25 years was performed. A work-up for JAK2 V617F mutation and thrombophilia was done. Medical charts and imaging tests were carefully reviewed. Three patients under the age of 22 were finally recruited. Two of those were found in life-threatening condition and improved clinically following treatment with bivalirudin, a direct thrombin inhibitor. It is conceivable that bivalirudin contributed to a favorable outcome of those patients in comparison to historical outcome previously reported. In conclusion, polycythemia vera in the young is not a mild disease since BCS, which is one of its complication, can be fatal even in those age group unrelated to the presence of hereditary thrombophilia. Once BCS occurs, we would suggest giving a trial with bivalirudin before an invasive procedure is planned.

Topics: Adolescent; Antithrombins; Budd-Chiari Syndrome; Child; Female; Hirudins; Humans; Janus Kinase 2; Liver; Male; Mutation; Peptide Fragments; Polycythemia Vera; Recombinant Proteins; Thrombin; Thrombophilia; Treatment Outcome; Young Adult

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Drug Administration Schedule; Drug Therapy, Combination; Endothelium, Vascular; Enoxaparin; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombophilia

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.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin