Abstract 14062: Cardiac Xenotransplantation-Associated Consumptive Thrombocytopenia is Attenuated With Use of Anti-CD40 Antibody Co-Stimulation Blockade
Introduction: Advances in the field of cardiac xenotransplantation may be able to address allogenic donor heart pool constraints. Costimulation blockade with anti-CD154 antibody is necessary to prevent xenograft rejection. However, this therapy has been found to be associated with critical consumptive thrombocytopenia, often limiting recipient survival. An alternative approach to costimulation blockade can be achieved with anti-CD40 therapy, without potentially evoking similar platelet consumption.
Hypothesis: We assessed the hypothesis that anti-CD40 antibody lessens post-xenotransplant thrombocytopenia and is associated with improved survival.
Methods: Baboons received heterotopic cardiac xenografts from genetically engineered swine. Immunosuppression comprised of conventional anti-rejection therapies along with either anti-CD154 or anti-CD40 antibody. Telemetry, video monitoring, and scheduled complete blood count panel were used to monitor recipients.
Results: Recipients treated with anti-CD154 (n=16) were found to have a 48.92% decrease in platelets within seven days of operation (p<0.001). Anti-CD40 treatment cohort (n=7) also had evidence of consumptive thrombocytopenia immediately following transplantation but this initial platelet count reduction was significantly less (23.39% decrease; p=0.02). Contrary to anti-CD154, anti-CD40 recipient platelet levels recovered from the initial decrease within two weeks. Anti-CD154 treated animals were observed to have a lower hematocrit postoperatively (32.17% vs 37.81%; p<0.001). Platelet counts <75K in the initial post-operative period was associated with increased risk of mortality within the first month (RR: 3.71; 95% CI 1.97, 6.99; p<0.001). Anti-CD40 cohorts did not experience platelet counts <50K or mortality secondary to hemorrhage.
Conclusions: In conclusion, the severity of consumptive thrombocytopenia is mitigated with anti-CD40 antibody therapy over anti-CD154. This novel regimen appears to have additional protection against consumptive thrombocytopenia and improve survival. The use of these techniques prove to be a significant advancement in the field of cardiac xenotransplantation and furthers the possibility of clinical application.
Author Disclosures: J.L. Chan: None. A.K. Singh: None. M.L. Thomas: None. D.L. Ayares: Employment; Significant; Currently an employee of Revivicor, Inc.. K.A. Horvath: None. M.M. Mohiuddin: None.
- © 2016 by American Heart Association, Inc.