Use of thrombolytic therapy in DCD liver transplantation does not seem to improve outcome

Abstract

The authors compared 100 consecutive donation after circulatory death (DCD) liver transplantations (LT) using a protocol that includes thrombolytic therapy (late DCD group) to a historical DCD group (early DCD group) and a cohort of donation after brain death (DBD) LT. The primary objective of the study was to "present the experience with 100 consecutive DCD LT using a protocol that includes tissue plasminogen activator (tPA) administration."While the team at Ochsner Clinic Foundation, New Orleans, deserves to be congratulated for their excellent results, we do have remarks about the added value of tPA, and we believe its advantages may have been overstated. Bohorquez et al justly recalls that Ischemic-type biliary lesions (ITBL)is the most feared and frequent cause of DCD allograft failure. However, they report a low ITBL rate in the late DCD LT. Noticeable is that the frequency of ITBL in the early versus late DCD LT does not statistically differ (5% vs. 3%, P = .63), and was extremely low in both groups. This makes it likely a result of other improvements, such as the reported short cold ischemia times, also explaining the low peak AST and thus less ITBL, 2 rather than a result of the usage of tPA.Interestingly, a significantly decreased number of retransplantations was shown (1% vs. 18.4%, P = .001). However, only one patient in the early DCD group received a retransplantation for ITBL. Other Lastly, although the clinical safety of using thrombolytic agents in DCD liver transplantation has been supported earlier by our study, in which urokinase (uPA) was used, we could not detect any benefit from the use of uPA, with an unchanged high rate of ITBL in our series (18% in control group vs. 17.5% in urokinase group; P = .68), accompanied by a longer cold ischemia time (572 minutes in control group vs. 535 minutes in study group; P = .09). 5In summary, we remain critical regarding the suggested effect of thrombolytic agents in reducing ITBL, and think that other factors, like the reported short ischemia times, may be the main explanation for the observed extremely low ITBL rates. DISCLOSUREThe authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Keywordsclinical research/practice, donors and donation: donation after brain death (DBD), donors and donation: donation after circulatory death (DCD), liver transplantation/hepatology, surgical technique, thrombosis and thromboembolism

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

“…4,11,14,25,26,32,33 Assessment of graft survival and biliary complications in DCD liver transplantation has shown that donor age, donor WIT greater than 30 minutes and CIT greater than 10 hours are highly predictive of poor graft outcomes compared to DBD liver transplantation. 4,14,25,30 In our present series, compared to patients in the early era, those in the late era had a significantly shorter time to cannulation and flush, lower WIT and a trend toward decreased CIT. These improvements likely explain the significant reductions in biliary complication rates achieved in the late era.…”

“…Although different groups have shown promising results with this practice, 28,29 recent evidence from a group in the Netherlands shows no reduction in nonanastomotic biliary strictures from the use of urokinase before liver transplantation. 30 We believe that the low rates of IC attributed to thrombolytic therapy are actually due to the multifactorial effect of accumulating experience with DCD liver transplantation (i.e., proper donor/recipient selection and shorter ischemic times). In our DCD liver transplantation protocol, we do not use thrombolytic therapy.…”

A cost analysis of early biliary strictures following orthotopic liver transplantation in the United States

“…Our previous work has shown that routine use of tPA in the setting of DCD transplant may be one cost‐effective strategy for prevention of NAS in this particularly susceptible population . Recently, however, other studies have called into question the role of microthrombi in biliary stricture development after DCD transplantation as well as the utility of tPA in reducing biliary stricture incidence DCD liver transplant recipients, pointing toward the need for a multi‐institution, randomized trial to more clearly assess the value of routine tPA use in DCD transplantation for prevention of biliary strictures …”

Foam fractionation for enhancing silica gel adsorption of urokinase from human urine

“…Urokinase (UK), a proteolytic enzyme that catalyzes the conversion of plasminogen to plasmin, has widespread applications in thrombolytic therapy . UK is often derived from human urine and animal cell culture, with the former serving as the major source .…”