88.16 Recovery for Post-Operative Coagulopathy in Liver Transplantation: Not A Platelet Mediated Event

P. J. Lawson1, H. B. Moore2, R. Choudhury2, C. Chang2, A. Kam2, E. Pomfret2, S. Mandell3, J. Pomposelli2, M. Chapman4, T. L. Nydam2  1University Of Colorado Denver,School Of Medicine,Aurora, CO, USA 2University Of Colorado Denver,Surgery-Transplant,Aurora, CO, USA 3University Of Colorado Denver,Anesthesiology,Aurora, CO, USA 4University Of Colorado Denver,Radiology,Aurora, CO, USA

Introduction:

Thrombocytopenia persists following liver transplantation (LT) and platelet recovery after LT remains poorly understood. Therefore, the aim of this study is to characterize the arachidonic acid (AA), thrombin (TRAP), and adenosine diphosphate (ADP) platelet functions during LT, in contrast to clot strength and fibrinogen contributions. We hypothesize that platelets regain functionality following transplantation, but not all agonists at the same time.

Methods:

Whole blood samples were drawn from baseline phase preoperatively through post-operative day 5 (POD5). Eleven liver transplant recipients consented for analysis with both thrombelastograpahy (TEG) and rotational thromboelastometry (ROTEM) platelet aggregometry. Assays included, TEG MA (clot strength), TEG angle (fibrinogen), and platelet counts in addition to platelet aggregometry with added AA, ADP, and TRAP agonists. Platelet function was estimated by the area under the curve (AUC). Measurements were contrasted to five healthy individuals. A paired Wilcoxon test was used to contrast transplant patients over time, and a Mann Whitney test was used to contrast transplant and control samples.

Results:

The median MELD score was 18. 64% of patients had baseline platelet counts less than 100,000. Clot strength was lowest during the anhepatic phase (P<0.05), returning to baseline by POD1 through POD5 (figure). Fibrinogen was lowest at 30 minutes after reperfusion (P<0.05), but regained baseline by POD1 (figure). Platelet counts remained low relative to baseline for POD1, 3, and 5 (85,000; 45,000; 51,000; 45,000. P<0.05). Platelet function of all three pathways reached their nadir during the anhepatic phase, and recovery began during reperfusion (figure). Platelet function improved by POD1 in all 3 pathways, but ADP was significantly low for POD3 (p=0.009) and 5 (p=0.036). AA and TRAP functions were depressed from POD1-5 but did not reach significance. Baseline platelet function did not differ from controls, but all three pathways were depressed by POD1 in transplant patients (p<0.05). TRAP regained function comparable to controls by POD5, but AA and ADP remained lower (P<0.001).

Conclusion:

Platelet agonist pathways were not upregulated following surgery in LT recipients. Patients regain baseline clot strength by POD1, despite a lower platelet count and suppressed function. Recovery in clot strength parallels an increase in fibrinogen while platelet function of the ADP and AA pathways remains suppressed through POD5. These measured coagulation derangements during and after LT warrant further investigation as current post-operative anti-thrombotic prophylaxis may be off target.

52.13 An Uncontrolled Donation After Cardiac Death Program Improves Access to Kidney Transplantation

R. Choudhury1, H. B. Moore1, K. Prins1, T. Nydam1  1University Of Colorado Denver,Transplant Surgery,Aurora, CO, USA

Introduction:  Uncontrolled donation after cardiac death (uDCD) is a novel method to increase the supply of kidney allografts.  As opposed to controlled DCD (cDCD), uDCD remains an underutilized practice in the United States.  Its use in Europe, primarily Spain, has largely been restricted to out of hospital cardiac arrests (OHCA) with limited volumes of recoverably allografts.  Given the high amount of unsuccessful resuscitations following trauma arrests (URTA) in the United States, various groups have suggested that this population should be included in a uDCD program.  Estimates vary as to the number of potential kidney allografts which could be gained with this method.  Furthermore, the impact on the rate of transplant and overall survival for a patient currently on the kidney transplant waitlist are unknown.  The objective of this study was to estimate the impact of uDCD on the rate of transplant, chance of remaining on dialysis, and death for end stage renal disease (ESRD) patients on hemodialysis in the United States.  

Methods:  A decision analytic Markov state transition model was created using medical decision-making software (DATA 3.5, TreeAge Software, Inc., Williamstown, MA) in order to simulate three clinical scenarios for a group of 60,000 ESRD patients on hemodialysis who do not have access to a living donor (20,000 in each group).  Three clinical scenarios were modeled: 1) Reject uDCD: Patients are on kidney transplant waitlist and will never accept a uDCD kidney, 2) OHCA simulation: On waitlist and will accept a OHCA uDCD kidney if available, whose availability is estimated from the high volume uDCD European center (Spain), and 3) UTRA simulation: On waitlist and will accept a URTA uDCD kidney if available, whose local availability is estimated from the experience of high volume level one trauma center in the United States (Denver Health).  Markov model transition probability were calculated from the literature for “Reject uDCD” and OHCA simulations, and were derived from chart review of Denver Health Medical Center for the UTRA simulation.

Results: A UTRA uDCD program increases the rate of patients who are transplant at five years (24.3%, UTRA vs 21.3%, OHCA, vs 20.2%, Reject uDCD).  Furthermore, patients who remain on dialysis are also reduced in the UTRA simulation.  However, 5 year all-cause mortality is similar among groups (28.1%, 28.2%, 28.3%).

Conclusion: uDCD improves access to transplant for ESRD patients on the kidney transplant waitlist.  However, all-cause mortality is similar for patients who reject uDCD suggesting that careful patient selection is required to match a potential uDCD kidney allograft to patients who would likely not be offered a transplant by any other means such that net utility may be gained.