Non-surgical postoperative bleeding after VAD implantation could be explained by an AVWD. Several pharmacologic treatment options (tranexamic acid, desmopressin, VWF-factor VIII concentrate, recombinant factor VIIa) may arise from our data. Improved VAD design could prevent this problem in the future.

Our data indicate that AVWS is a typical disorder in patients with ECLS. We hypothesize that AVWS could contribute to aggravation of bleeding tendencies in ECLS patients.

The AVWS is present already in the early postoperative phase after VAD implantation. Therefore, reduced shear stress has to be an important feature of newly developed assist devices in the future.

While severe haemolysis accompanies BVAD support, erythrocyte damage is less pronounced in the axial LVAD examined and only slight in the intracorporeal centrifugal LVAD. Haemopexin, a scavenger of free haemoglobin, can be used, in combination with haptoglobin and free haemoglobin, to assess erythrocyte damage.

Wound complications following median sternotomy remain a challenge to cardiac surgery. Redo and emergency operations are the most important risk factors in this contemporary series. More efforts seem mandatory to decrease this arduous morbidity and the costs of prolonged treatment.

Ferredoxins (FDX) and the FDX:NADP+ oxidoreductase (FNR) represent a key junction of electron transport downstream of photosystem I (PSI). Dynamic recruitment of FNR to the thylakoid membrane has been considered as a potential mechanism to define the fate of photosynthetically derived electrons. In this study, we investigated the functional importance of the association of FNR with the photosynthetic apparatus in Chlamydomonas reinhardtii. In vitro assays based on NADP+ photoreduction measurements as well as NMR chemical shift perturbation analyses showed that FNR preferentially interacts with FDX1 compared to FDX2. Notably, binding of FNR to a PSI supercomplex further enhanced this preference for FDX1 over FDX2, suggesting that FNR is potentially capable of channelling electrons towards distinct routes. NADP+ photoreduction assays and immunoblotting revealed that the association of FNR with the thylakoid membrane including the PSI supercomplex is impaired in the absence of Proton Gradient Regulation 5 (PGR5) and/or Proton Gradient Regulation 5-Like photosynthetic phenotype 1 (PGRL1), implying that both proteins, directly or indirectly, contribute to the recruitment of FNR to the thylakoid membrane. As assessed via in vivo absorption spectroscopy and immunoblotting, PSI was the primary target of photodamage in response to high-light stress in the absence of PGR5 and/or PGRL1. Anoxia preserved the activity of PSI, pointing to enhanced electron donation to O2 as the source of the observed PSI inactivation and degradation. These findings establish another perspective on PGR5/PGRL1 knockout-related phenotypes and potentially interconnect FNR with the regulation of photosynthetic electron transport and PSI photoprotection in C. reinhardtii.

BackgroundThe number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II.Methods and ResultsIn this study, we investigated the prevalence and onset of AVWS in 198 VAD patients. To our knowledge, this is the largest cohort of VAD patients whose longitudinal data on AVWS have been collected. We also analyzed whether AVWS is less severe in HM III patients than in HeartMate II patients. Because platelet dysfunction can raise the bleeding risk, we investigated platelet function in a subset of patients. In total, 198 VAD patients and 60 patients with heart transplants as controls were included in this study. The ratio of von Willebrand factor collagen binding capacity to von Willebrand factor:antigen, multimer analyses, and platelet function (especially secretion of α‐ and δ‐granules) were investigated. All 198 VAD patients developed AVWS. As soon as the VAD was explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III patients than in the HeartMate II patients. The HM III patients had fewer bleeding symptoms. In addition, VAD patients exhibited a platelet α‐ and δ‐granule secretion defect.Conclusions AVWS develops in VAD patients and may increase the bleeding risk. The HM III device causes less severe AVWS. Platelet secretion defects should be investigated in VAD patients because they also raise the bleeding risk.Clinical Trial Registration https://www.drks.de/drks_web. Unique identifier: DRKS00000649.

No abstract