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Sunder T, Thangaraj PR, Kuppusamy MK. Venous thromboembolism following lung transplantation. World J Transplant 2025; 15:99241. [DOI: 10.5500/wjt.v15.i2.99241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/12/2024] [Accepted: 11/14/2024] [Indexed: 02/21/2025] Open
Abstract
Lung transplantation (LT) is currently a surgical therapy option for end-stage lung disease. Venous thromboembolism (VTE), which can occur after LT, is associated with significant morbidity and mortality. Because of improved outcomes, increasing numbers of patients are receiving LT as treatment. Patients on the waitlist for LT tend to be older with weakness and frailty in addition to pulmonary symptoms. These factors contribute to a heightened risk of postoperative VTE. Furthermore, patients who clinically deteriorate while on the waitlist may require extra corporeal membrane oxygenation as a bridge to LT. Bleeding and thromboembolism are common in these patients. Pulmonary embolism (PE) in a freshly transplanted lung can have significant effects leading to morbidity and mortality. PE typically leads to impairment of gas exchange and right ventricular strain. In LT, PE can affect healing of bronchial anastomosis and may even contribute to the development of chronic allograft lung dysfunction. This article discussed the incidence, clinical features and diagnosis of VTE after LT. Furthermore, the treatment modalities, complications, and outcomes of VTE were reviewed.
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Affiliation(s)
- Thirugnanasambandan Sunder
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
| | - Paul Ramesh Thangaraj
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
| | - Madhan Kumar Kuppusamy
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
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Concannon K, Huntsman R, Cole K, Kennedy C, Rosenbaum A, Lemke A. Concurrent Apixaban With Itraconazole or Posaconazole Pharmacokinetic and Clinical Outcome Evaluation in Cardiothoracic Transplant Recipients. Clin Transplant 2025; 39:e70165. [PMID: 40294102 DOI: 10.1111/ctr.70165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 03/24/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025]
Abstract
Itraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents' potent CYP3A4 inhibition, and literature describing concurrent apixaban, a CYP3A4 substrate, is limited. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34-230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95-195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93-174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced-dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.
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Affiliation(s)
- Kennedy Concannon
- Department of Pharmacy, Mayo Clinic Hospital, Rochester, Minnesota, USA
| | - Rachel Huntsman
- Department of Pharmacy, Mayo Clinic Hospital, Rochester, Minnesota, USA
| | - Kristin Cole
- Division of Clinical Trials and Biostatistics, Mayo Clinic Hospital, Rochester, Minnesota, USA
| | - Cassie Kennedy
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Hospital, Rochester, Minnesota, USA
| | - Andrew Rosenbaum
- Division of Cardiovascular Diseases, Mayo Clinic Hospital, Rochester, Minnesota, USA
| | - Adley Lemke
- Department of Pharmacy, Mayo Clinic Hospital, Rochester, Minnesota, USA
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Marazzato J, Eikermann M, Di Biase L. Management of Atrial Arrhythmias After Lung Transplant. JACC Clin Electrophysiol 2023; 9:1824-1835. [PMID: 37648342 DOI: 10.1016/j.jacep.2023.01.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 12/21/2022] [Accepted: 01/18/2023] [Indexed: 09/01/2023]
Abstract
The overall survival in patients undergoing lung transplantation is poor. Although postsurgical atrial arrhythmias seem to play a major role in the morbidity and mortality of this population, data regarding the clinical and interventional management of this complication are still controversial. Through a review of the literature in the field, we observed that not only the surgical technique is clearly arrhythmogenic, but the new administration of peri-procedure beta-blockers and amiodarone for arrhythmia prevention and treatment, respectively, seems harmful in these postsurgical patients. However, low-dose beta-blockers administered after surgery seem feasible in arrhythmia prevention in specific patient subgroups, and, aside from amiodarone, alternative antiarrhythmic agents can be safely and effectively used to treat symptomatic patients on top of adequate rate control. Finally, as to complex atrial arrhythmias occurring late after lung transplant surgery, radiofrequency catheter ablation seems a feasible treatment option. In light of this evidence and considering the absence of clear recommendations in the field, we suggest a practical approach that may help the clinician in the management of this postsurgical complication. However, as most of these considerations are drawn from small-sized and retrospective studies, more evidence is needed in the future to clarify which medical and interventional strategies may best treat these postsurgical arrhythmias and thus potentially improve the outcome of these frail patients.
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Affiliation(s)
- Jacopo Marazzato
- Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA; Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Matthias Eikermann
- Department of Anesthesiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, USA; Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Essen, Germany
| | - Luigi Di Biase
- Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
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Nikodem A, Arjuna A, Hu C, Nasar A, Lam JC, Cherrier L. Apixaban for Treatment of Atrial Fibrillation and Venous Thromboembolism After Lung Transplantation. Prog Transplant 2023; 33:175-181. [PMID: 36942381 DOI: 10.1177/15269248231164173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
INTRODUCTION Guidelines recommend the use of direct oral anticoagulation therapy over warfarin for the treatment of venous thromboembolism and atrial fibrillation. However, there is uncertainty and a lack of data supporting the safety and efficacy of anticoagulation therapy in lung transplant recipients. Additionally, there are unique considerations for this population, such as labile renal function and drug interactions. PROJECT AIMS The objective of this program evaluation was to evaluate the safety and efficacy of apixaban therapy for atrial fibrillation and venous thromboembolism in lung transplant recipients. DESIGN Medical records of all adult lung transplant recipients who received apixaban for atrial fibrillation or venous thromboembolism treatment between January 1, 2018, and August 31, 2020 were retrospectively reviewed. Safety was evaluated by the incidence of bleeding. Efficacy was evaluated by the recurrence of blood clots or the incidence of stroke. RESULTS A total of 134 recipients were included in the review. Thromboembolisms occurred in 14 recipients (10%), and none experienced a stroke. Bleeding occurred in 12 recipients (9%). CONCLUSIONS The results of this evaluation were similar to those seen in smaller studies of the safety and efficacy of direct oral anticoagulation therapy for the treatment of atrial fibrillation or venous thromboembolism in lung transplant recipients, especially in recipients taking interacting azole antifungals. Prospective, comparative studies are needed to confirm these findings.
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Affiliation(s)
- Anne Nikodem
- Department of Pharmacy, 6586St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Ashwini Arjuna
- Department of Pulmonology, Norton Thoracic Institute, 6586St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Chengcheng Hu
- Department of Epidemiology and Biostatistics, 48710University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, AZ, USA
| | - Aasya Nasar
- Department of Pharmacy, 6586St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Jade C Lam
- Department of Pharmacy, 6586St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Lauren Cherrier
- Department of Pharmacy, 6586St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
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A Review of Direct-acting Oral Anticoagulants and Their Use in Solid Organ Transplantation. Transplantation 2022; 106:2143-2154. [PMID: 35642975 DOI: 10.1097/tp.0000000000004195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Direct-acting oral anticoagulant (DOAC) use has increased dramatically since their introduction because of the growing evidence of proven efficacy and enhanced safety compared with warfarin and the low-molecular-weight heparins in the general population. Unfortunately, there is a dearth of quality data regarding the safety and efficacy of the DOACs in patients awaiting organ transplant and those who received a solid organ transplant. This review aims to evaluate the available literature and considerations regarding anticoagulation use in transplant recipients, focusing on preoperative, perioperative, and postoperative DOAC use.
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Mansell H, Shoker A, Alcorn J, Fenton ME, Tam JS, Semchuk W, Bashir B, Kraft WK, Yao S, Douketis JD. Pharmacokinetics of Apixaban and Tacrolimus or Cyclosporine in Kidney and Lung Transplant Recipients. Clin Transl Sci 2022; 15:1687-1697. [PMID: 35439353 PMCID: PMC9283751 DOI: 10.1111/cts.13284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 03/18/2022] [Accepted: 03/31/2022] [Indexed: 11/29/2022] Open
Abstract
Apixaban is frequently used off‐label in transplant recipients. However, a potential drug interaction exists with the calcineurin inhibitors. We conducted an open‐label drug–drug interaction study to determine the pharmacokinetics of apixaban in lung and kidney transplant recipients who were taking a calcineurin inhibitor. A single dose of apixaban 10 mg was administered orally to kidney and lung transplant recipients maintained on either tacrolimus or cyclosporine, and pharmacokinetic parameters were compared to a reference cohort of 12 healthy subjects who used the same apixaban dose and pharmacokinetic blood sampling. Fourteen participants were enrolled (n = 6 kidney, n = 8 lung), with 10 maintained on tacrolimus and four on cyclosporine. Data from 13 participants was usable. Participants were taking triple therapy immunosuppression and had a mean (SD) of 12 (3) medications. Participants receiving tacrolimus and cyclosporine had area under the plasma concentration–time curve from time zero to infinity (AUC0‐inf) geometric least square means (90% confidence interval [CI]) of 4312 (95% CI 3682, 5049) and 5388 (95% CI 3277, 8858), respectively. Compared to healthy subjects, the associated geometric mean ratios (GMRs) for apixaban maximum plasma concentration (Cmax), AUC from time zero to the last quantifiable concentration (AUC0‐tlast) and AUC0‐inf were 197% (95% CI 153, 295), 244% (95% CI 184, 323), and 224% (95% CI 170, 295) for transplant recipients on tacrolimus. The GMR (90% CI) Cmax, AUC0‐tlast, and AUC0‐inf of apixaban for patients on cyclosporine were 256% (95% CI 184, 358), 287% (95% CI 198, 415), and 280% (95% CI 195, 401). Kidney and lung transplant recipients receiving tacrolimus had higher apixaban exposure. A similar trend was noted for patients receiving cyclosporine, but additional patients are needed to confirm this interaction. Future studies are needed before apixaban can be safely recommended in this population, and the impact of dose staggering should be investigated. This study highlights the importance of pharmacokinetic studies in actual patient populations.
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Affiliation(s)
- Holly Mansell
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Ahmed Shoker
- Divison of Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Jane Alcorn
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Mark E Fenton
- Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Julian S Tam
- Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - William Semchuk
- Pharmacy Services, Saskatchewan Health Authority, Regina, SK, Canada
| | - Babar Bashir
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Walter K Kraft
- Dept. of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA
| | - Shenzhen Yao
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - James D Douketis
- Dept. of Medicine, St. Joseph's Healthcare Hamilton and McMaster University, Hamilton, ON, Canada
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