Exploring NT-proBNP, syndecan-1, and cytokines as biomarkers for transfusion-associated circulatory overload in a critically ill patient population receiving a single-unit red blood cell transfusion.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is an often underdiagnosed pulmonary transfusion complication. A biomarker could aid with the diagnosis. To date, B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) seem the most promising biomarkers in the general hospital population. The aim was to evaluate NT-proBNP as a biomarker for TACO in a critically ill patient population and explore syndecan-1 and cytokines as other potential biomarkers. STUDY DESIGN AND METHODS: A retrospective study was performed using samples and clinical data collected during a prospective observational study. Adult patients admitted to the intensive care and transfused with a single red blood cell unit were included. TACO cases were retrospectively identified using a case definition based on the current TACO definition. The primary biomarker was NT-proBNP, also we measured syndecan-1 IL-6, IL-8, and IL-10. All markers were measured directly before transfusion, 1 and 24 h after transfusion. RESULTS: Our cohort included 64 patients, 12 of which were identified as TACO patients. TACO patients had a lower PaO2 /FiO2 ratio and were more often ventilated following transfusion compared to non-TACO patients. There was no significant difference in NT-proBNP between pre- and post-transfusion levels nor between TACO and non-TACO patients. Syndecan-1 was significantly elevated in TACO patients both pre- and post-transfusion compared to non-TACO patients. DISCUSSION: NT-proBNP was not associated with TACO in this critically ill patient population. Interestingly, levels of syndecan-1 were increased in TACO patients at baseline. More research is needed to clarify this association and its possibilities as a biomarker to predict patients at risk for TACO.

Circular RNA Sequencing of Maternal Platelets: A Novel Tool for the Identification of Pregnancy-Specific Biomarkers.

BACKGROUND: In the first trimester of pregnancy, the maternal platelet is directly involved in a positive feedback mechanism that facilitates invasion of the extravillous trophoblast into the maternal spiral arteries. Dysfunctional trophoblast invasion with defective deep placentation is primordial in the etiology of the "great obstetrical syndromes." METHODS: In this proof-of-concept study, using transcriptome analysis of circular RNA (circRNA) following RNA sequencing of maternal platelets, we tested whether pregnancy-specific circRNA markers could be identified in the first trimester of normal pregnancies. Differential transcript expression analysis of circRNAs, as predicted by Accurate CircRNA Finder Suite, CircRNA Identifier (version 2), and Known and Novel Isoform Explorer, was done using thromboSeq.R with variation of multiple settings. Test performance was checked for (a) de novo circRNA identification using the novel platelet-specific Plt-circR4 as a positive control, (b) complete segregation of groups (pregnant vs nonpregnant) after heat map-dendrogram clustering, (c) identification of pregnancy-specific circRNA markers at a false discovery rate (FDR) <0.05, and (d) confirmation of differentially expressed circRNA markers with an FDR <0.05 by an independent method, reverse transcription-quantitative PCR. RESULTS: Of the differentially expressed circRNAs with P values <0.05, 41 circRNAs were upregulated (logFC >2), and 52 circRNAs were downregulated (logFC less than -2) in first-trimester platelet RNA. Of these, nuclear receptor-interacting protein 1 circRNA covering exons 2 and 3 of the 5'-untranslated region was pregnancy specific with upregulation in first-trimester maternal platelets compared to nonpregnant controls. CONCLUSION: CircRNA sequencing of first-trimester maternal platelets permits the identification of novel pregnancy-specific RNA biomarkers. Future use could include the assessment of maternal and fetal well-being.