Venous Thromboembolic Disease after Lung Transplantation: Special Focus on Sirolimus

Abstract

Background: Venous thromboembolism (VTE) is common after lung transplantation. We aimed to review our experience with VTE in lung transplant recipients, while paying attention to the use of sirolimus, a novel immunosuppressive agent that may have prothrombotic effects. Methods: A retrospective review of lung transplant recipients at the University of Pennsylvania from 2000 to 2006 was performed. Demographic data, acute and chronic rejection and survival were included. Clinically apparent VTE episodes and sirolimus utilization were noted. Results: 59/278 (21.2%) of patients developed VTE. There were no baseline differences in patients with and without VTE. Patients more than three months post-transplant had a higher rate of VTE on sirolimus vs. off (1.98% vs. 0.32% per month on vs. off sirolimus; p<0.001). Patients with VTE after lung transplantation had worse survival (p=0.001). Conclusions: VTE is a common complication after lung transplantation and patients with VTE have worse post-transplant survival. Sirolimus is associated with increased rate of VTE.

Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients

“…There are discordant data in the transplant literature regarding whether sirolimus is prothrombotic. Our findings are consistent with two recently published studies suggesting an associa-tion between sirolimus use and VTE in lung transplant recipients (29,30). An increased risk of thrombotic events has also been noted with the use of sirolimus in liver transplant recipients.…”

“…Sirolimus has associated toxicities . Recent studies have found an increased risk of venous thromboembolism (VTE) in lung transplant recipients receiving sirolimus both in a retrospective review and a prospective, randomized, open‐label study comparing immunosuppressive regimens . In addition, the FDA issued a black box warning in 2002 stating that de novo use of sirolimus in liver transplant recipients may be associated with hepatic artery thrombosis based on preliminary results of two multicenter phase II/III trials .…”

Increased risk of venous thromboembolism with a sirolimus-based immunosuppression regimen in lung transplantation

“…This finding was unexpected and supports the hypothesis from a recently published small, single-center, retro- spective study suggesting an association between SIR use and VTE. 13 SIR, also known as rapamycin, is a potent immunosuppressive drug that is increasingly being used for the prevention and treatment of acute and chronic allograft rejection after solidorgan transplantation. This drug exerts its biologic effects by binding to and inhibiting the mammalian target of rapamycin (mTOR), a critical intracellular regulatory kinase involved in protein translation, cell growth and proliferation, angiogenesis and adaptive processes necessary for cell survival during stress.…”

“…9 -12 After observing several unexpected cases of venous thromboembolism (VTE) in lung transplant recipients receiving sirolimus, investigators at the University of Pennsylvania retrospectively reviewed and reported on their single-center experience and found a possible association between SIR use and an increased risk of VTE. 13 Although VTE is not uncommon after lung transplantation, its association with a particular immunosuppressive regimen has not been previously reported. 14 -16 To further investigate the question of whether or not SIR increases the risk of VTE, we analyzed data from a recently completed, large, multicenter, prospective, randomized, open-label study of 181 lung transplant recipients comparing acute rejection, chronic rejection, and survival rates between a cohort of patients who received azathioprine (AZA), tacrolimus (TAC), and prednisone (PRED) (Group 1) for maintenance immunosuppression versus a cohort that received SIR, TAC, and PRED (Group 2).…”

Prophylaxis with enoxaparin for prevention of venous thromboembolism after lung transplantation: a retrospective study

“… described DVT as a risk factor for patient survival (HR 2.43; 95% CI, 1.29–4.64), and Lingaraju et al . found VTE to be associated with poorer survival 3 months after LT.…”