A Novel Post-Transplant Multimodal Antibody Management Protocol for Highly Sensitized Lung Transplant Recipients

Abstract

Lung transplant recipients (LTRs) are at an increased risk for venous thromboembolism (VTE) after transplant, necessitating the use of anticoagulation. Guidelines recommend direct oral anticoagulants (DOACs) over warfarin for most patients and indications; however, many of the studies upon which these recommendations were made excluded high-risk patient populations, including transplant recipients. The purpose of this study was to compare rates of new or recurrent VTE and bleeding in patients receiving DOAC versus warfarin after lung transplant. Methods: This retrospective cohort study was approved by the local institutional review board. Adult lung transplant recipients transplanted at a single center from 2010 -2018 who received an oral anticoagulant for treatment of VTE were included. Re-transplants, patients with a diagnosis of atrial fibrillation/flutter, and those taking oral anticoagulation prior to transplant were excluded. The primary outcome was new or recurrent VTE within 1 year of starting oral anticoagulation, as determined by review of radiology reports. Safety was evaluated by assessment of 1-year rate of bleeding requiring emergency department visit or admission. Propensity matching in a 1:1 ratio using was used to control for confounders. Variables chosen for inclusion in the propensity score were sex, age, and chronic kidney disease. Clinical outcomes were assessed using chi-2 or Fisher's exact test. Results: 366 LTRs met inclusion criteria. Of these, 68 received DOACs and 298 received warfarin. The analysis cohort included 132 LTRs who were successfully propensity matched, 66 in each group. After matching, patient demographics and comorbidities were similar at baseline. In the 1-year follow up period, 17 patients (12.9%) experienced new or recurrent VTE. There was no difference in the rate of VTE between the DOAC and warfarin groups (13.6% vs 12.1%, p=0.80). Six total bleeding events requiring hospital visits were observed, 4 in the DOAC group and 2 in the warfarin group (p=0.68).

Lung Transplantation and the Era of the Sensitized Patient

“…Treated patients had a significantly decreased waitlist time compared with historical controls. Of note, several infectious complications were noted ( 42 ).…”

“…Of note, two infectious complications were reported which resolved with treatment ( 47 ). To date, the small cohort described in lung candidate above is the only known use of CD28 co-stimulation blockade in multimodal lung transplant desensitization protocols and larger scale trials are needed ( 42 ). The higher immunosuppressive effects are attractive in highly allosensitized patients, however safety and efficacy data are yet to be seen ( 48 ).…”