Platelet concentrates (PCs) are frequently used to prevent and treat bleeding in patients. However, their efficacy is reduced during inflammation as well as due to platelet storage lesion, including metabolomic shifts and changes in surface markers of stored PCs. This study aims to identify disparities between short- and long-term stored PCs during controlled inflammation, focusing on distinct metabolic pathways, alterations in surface markers and posttransfusion recovery (PTR). Twenty-four male participants received lipopolysaccharide or saline as control after an autologous transfusion of either short- (2 days) or long-term (7 days) stored PCs. Metabolomics and surface markers of these transfused PCs were assessed before transfusion using mass spectrometry and flow cytometry, respectively. Biotin-labeled platelets were used to assess surface markers after transfusion and determine PTR. Before transfusion, short-term stored PCs demonstrated increased glycolysis, pentose phosphate pathway activity, dense granule components (eg, serotonin, adenosine diphosphate, and epinephrine), and purine, arginine, and tryptophan metabolism. In contrast, long-term stored PCs exhibited elevated transsulfuration and taurine metabolism, along with higher levels of CD62P and CD63. During inflammation, a decreased PTR was found, particularly in long-term stored PCs. Higher expression of dense granule metabolite components and lower CD62P and lactate levels were correlated with improved PTR. Differences in metabolic pathways, surface markers, and PTR were identified between short- and long-term stored PCs in a controlled human experiment, suggesting a preference for the use of short-term stored PCs during inflammation. This trial was registered at the International Clinical Trials Registry Platform (https://trialsearch.who.int/) as #NL-OMON26852.

Extracorporeal membrane oxygenation (ECMO) can be a life-saving intervention, but it is associated with high complication rates. ECMO induces systemic inflammation and endothelial hyperpermeability, thereby causing tissue edema, microcirculatory perfusion disturbances, and organ failure. This study investigated whether the inhibition of vascular endothelial protein tyrosine phosphatase (VE-PTP), a regulator of endothelial permeability, reduces extracorporeal circulation (ECC)-induced microvascular dysfunction. Rats were subjected to ECC after treatment with Razuprotafib (n = 11) or a placebo (n = 11), or they underwent a sham procedure (n = 8). Razuprotafib had no effect on the ECC-induced impairment of capillary perfusion, as assessed with intravital microscopy, nor did it influence the increased wet-to-dry weight ratio in kidneys, a marker of edema associated with ECC. Interestingly, Razuprotafib suppressed the ECC-induced increase in TNFα, whereas angiopoietin-2 even further increased, following the discontinuation of ECC. Circulating interleukin-6, ICAM-1, angiopoietin-1, and soluble Tie2 and tissue VE-PTP, Tie1, and Tie2 mRNA expression were not affected by Razuprotafib. Furthermore, Razuprotafib improved the PaO₂/FiO₂ ratio and reduced histopathological pulmonary interstitial inflammation following ECC compared to the placebo. To conclude, treatment with Razuprotafib did not improve ECC-induced microcirculatory perfusion disturbances nor renal edema.

Background: Transfusion‐associated circulatory overload (TACO) accounts for 35% of transfusion‐related fatalities. Previous pre‐clinical studies explored plasma and red blood cell transfusion in TACO, but the effect of platelets remains unexplored. Platelet transfusions have the highest rate of adverse reactions and are associated with increased mortality in TACO patients. We aimed to determine whether platelet transfusion induces circulatory overload compared to crystalloids and whether it causes a more severe phenotype than plasma in a TACO rat model of myocardial infarction (MI).Methods: A validated TACO model in anemic Wistar rats with MI was used. Animals received platelets (n = 11), plasma (n = 10), or Ringer's lactate (n = 11). Pulmonary capillary pressure was assessed via left‐ventricular end‐diastolic pressure (LVEDP). The primary outcome was the change in LVEDP (ΔLVEDP) following transfusion. Secondary outcomes included pulmonary wet/dry weight ratio, oxygen tension or partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) ratio, and circulating biomarkers.Results: ΔLVEDP following platelet transfusion (10.4 ± 4.6 mmHg) was significantly greater than Ringer's lactate (0.9 ± 1.4 mmHg; p < .001), but similar to plasma (13.0 ± 7.7 mmHg; p > .5). Pulmonary wet/dry weight ratios were comparable across groups (p > .5). At termination, PaO₂/FiO₂ ratio was significantly lower after platelet transfusion (372 ± 48) compared to Ringer's Lactate (447 ± 79; p < .05). N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) did not differ between groups at termination (p > .1). However, NT‐proBNP significantly increased from baseline (50 ± 24 pg/mL) to termination (177 ± 86 pg/mL) across all groups (p < .001).Discussion: Platelet transfusion induces circulatory overload in a TACO rat model with heart failure when compared to crystalloids, showing a trend toward reduced oxygenation compared to plasma transfusion. Further investigation is needed to determine the pathophysiological mechanisms.