OC 53.2 - Does Plasminogen Replenishment Correct Recovery from Fibrinolysis Resistance Following Liver Transplantation?

Tuesday, June 27, 2023

11:00 – 11:15 ET

Room: 520

Session Available As: On-Demand

Presenting Author(s)

Hunter B. Moore, MD, PhD (he/him/his)

Assistant Professor
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States

Co-Author(s)

IR

Ivan E. Rodriguez

Research Fellow
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States
WL

Wells B. LaRiviere

MD-PhD Student
University of Colorado
Aurora, Colorado, United States
KB

Kristen Brown

Research Services Professional
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States
KH

Kyndall Hadley

Research Services Professional
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States
JP

James Pomposelli

Professor
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States
EP

Elizabeth Pomfret

Professor
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States
TN

Trevor Nydam

Associate Professor
Division of Transplant Surgery, University of Colorado School of Medicine
Aurora, Colorado, United States

Background: Resistance to tissue plasminogen activator(PLAT) quantified by thrombelastography(TEG) following liver transplant(LT) is associated with early allograft dysfunction(EAD) and graft loss. The mechanism remains unclear.

Aims: LT recipients commmonly develop systemic hyperfibrinolysis during surgery and are anticipated to have plasminogen (PLG) depletion as a cause of fibrinolysis resistance after surgery. We hypothesize that exogenous PLG added to the TEG would correct PLAT resistance and demonstrate comparable outcomes within the fibrinolysis resistance cohort outcomes, suggesting a therapeutic role of PLG.

Methods: LT recipients were enrolled in an observational study to evaluation peri-operative fibrinolytic changes. Postoperative blood samples were run with TEG with PLG(50 μg/mL), PLAT(tPA 75ng/ml), and PLG + PLAT(same concentrations). Resistance to PLAT was defined as the lysis at 30 minutes (LY30) =0% in at PLAT TEG, based on the previously validated threshold. Rescue with PLAT was defined as PLAT TEG LY30=0% with a PLAT +PLG TEG LY30>0%. Outcomes assessed were EAD based on postoperative labs and graft loss.

Results: 135 patients with a median MELD 22 were included. EAD occurred in 28% of patients, and graft loss was 11%. Resistance to PLAT was present in 57% of patients. Within this cohort, 28% of patients were rescued with PLG. PLAT resistance was associated with a three-fold rate of EAD (40% vs 12% P< 0.001) and graft loss (15% vs 5% P=0.065). PLAT resistance that was PLG rescue versus non, had lower EAD rates (15% vs 48% P< 0.001) and less graft loss (5% vs 19% P=0.042).

Conclusion(s): PLAT resistance quantified by TEG not rescued by PLG is associated with a higher rate of EAD and graft loss than the PLG rescue cohort, which had similar outcomes to the non-fibrinolysis resistant patients. PLG supplementation following LT for PLAT resistance does not appear to be a therapeutic target for treating this patient population.

Learning Objectives:

Define the prevalance of fibrinolysis resistance follow liver transplant attributable to plasminogen deficiency
Differenciate outcomes in patient with fibrinolysis resistance following liver transplant that is correctable versus non correctable via plasminogen supplementation
Generate a differential for mechanisms that can cause fibrinolysis resistance following liver transplantation