Bleeding and thrombotic events in post-cardiotomy extracorporeal life support.

OBJECTIVES: Haemorrhagic and thrombotic complications are known obstacles in extracorporeal life support (ECLS), and patients requiring post-cardiotomy (PC)-ECLS are particularly prone. The objective of this study was to characterize the incidence, type and clinical relevance of bleeding and thrombotic events in patients on PC-ECLS. METHODS: A total of 504 patients receiving PC-ECLS between 2000 and 2021 at a single centre were included in a retrospective analysis. Incidence and type of haemorrhagic and thrombotic complications in patients on PC-ECLS were assessed. Overall survival was compared, and perioperative risk factors for bleeding and thrombotic events were assessed by binary logistic regression. RESULTS: Of the 504 patients requiring PC-ECLS, 196 patients (38.9%) had 235 bleeding events [surgical site: n = 135 (26.8%); cannulation site: n = 68(13.4%); requiring surgical revision: n = 39 (7.7%); cannulation site change: n = 17 (3.4%); fatal cannulation site bleeding: n = 4(0.8%); intracranial haemorrhage: n = 11 (2.1%); gastrointestinal haemorrhage: n = 8 (1.6%); pulmonary haemorrhage: n = 8 (1.6%); and intra-abdominal/retroperitoneal haemorrhage: n = 5 (1%)]. Overall mortality was higher in patients with major bleeding complications than in patients without bleeding complications (P < 0.0001).A total of 74 patients (14.7%) had 84 thrombotic events [ischaemic stroke, n = 39 (7.7%); cannula/circuit thrombosis, n = 26 (5.2%); peripheral embolism, n = 11 (2.2%); device exchange for haemolysis, n = 8 (1.6%)]. Another 246 patients (48.8%) had at least 1 haemocompatibility-related adverse event. Preoperative dual antiplatelet therapy [adjusted odds ratio (OR): 1.83, 95% confidence interval (CI): 1.063-3.137] and ECLS duration (adjusted OR: 1.14, 95% CI: 1.086-1.197) were identified as independent risk factors for haemorrhage. Prior stroke/transient ischaemic attack (adjusted OR: 1.91, 95% CI: 1.08-3.83) and ECLS duration (adjusted OR: 1.09, 95% CI: 1.04-1.15) were identified as risk factors for thrombotic events. CONCLUSIONS: Bleeding complications in patients on ECLS are common and significantly impair survival. Nearly half of the patients were affected by any haemocompatibility-related event.

In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome.

CTLA4Ig has been shown to improve kidney allograft function, but an increased frequency of early rejection episodes poses a major obstacle for more widespread clinical use. The deleterious effect of CTLA4Ig on Treg numbers provides a possible explanation for graft injury. Therefore, we aimed at improving CTLA4Ig's efficacy by therapeutically increasing the number of Tregs. Murine cardiac allograft transplantation (BALB/c  to B6) was performed under CTLA4Ig therapy modeled after the clinically approved dosing regimen and Tregs were transferred early or late after transplant. Neither early nor late Treg transfer prolonged allograft survival. Transferred Tregs were traceable in various lymphoid compartments but only modestly increased overall Treg numbers. Next, we augmented Treg numbers in vivo by means of IL2 complexes. A short course of IL2/anti-IL2-complexes administered before transplantation reversed the CTLA4Ig-mediated decline in Tregs. Of note, the addition of IL2/anti-IL2-complexes to CTLA4Ig therapy substantially prolonged heart allograft survival and significantly improved graft histology on day 100. The depletion of Tregs abrogated this effect and resulted in a significantly diminished allograft survival. The increase in Treg numbers upon IL2 treatment was associated with a decreased expression of B7 on dendritic cells. These results demonstrate that therapy with IL2 complexes improves the efficacy of CTLA4Ig by counterbalancing its unfavorable effect on Tregs.