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Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion.

ABSTRACT: The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-?2-antiplasmin complex (PAP), and D-dimer in humans. Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 ?g/mL) to induce plasmin generation required for PAP and D-dimer formation. Serum transfusions (50 mL/30 min) were well tolerated by all subjects. Endogenous thrombin formation was not induced by serum infusions as measured using a highly sensitive oligonucleotide-based enzyme capture assay. Median peak levels (x-fold increase over baseline) of F1+2, TAT, PAP, and D-dimer of 3.7 nmol/L (28.9), 393 ng/mL (189.6), 3,829 ng/mL (7.0), and 13.4 mg/L (34.2) were achieved at the end of serum infusions. During a 48 h lasting follow-up period all biomarkers showed elimination kinetics of a two-compartment model. Median (interquartile range) terminal half-lives were 1.9 (1.3-3.6) h for F1+2, 0.7 (0.7-2.6) h for TAT, and 10.8 (8.8-11.4) h for PAP. With 15.8 (13.1-23.1) h the D-dimer half-life was about twice as long as previously estimated from radiolabeling studies in animals and small numbers of human subjects. The serum approach presented here allows label-free and simultaneous analysis of the elimination kinetics of various hemostasis-related biomarkers. Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system.

SUBMITTER: Ruhl H

PROVIDER: S-EPMC4684386 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion.

Rühl Heiko H Berens Christina C Winterhagen Anna A Müller Jens J Oldenburg Johannes J Pötzsch Bernd B

PloS one 20151214 12

The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PAP), and D-dimer in humans. Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 μg/mL) to induce plasmin generation ...[more]

PMID: 26658824

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Project description:This study aimed to identify secreted protein biomarkers in serum from the label-free LC/MS proteomics of neutrophils in pulmonary tuberculosis (TB) patients for the diagnosis biomarkers of TB label-free LC/MS. The proteomic profiles of neutrophils from 15 active TB patients and 15 healthy controls (HCs) were analyzed using label-free LC/MS. We identified 358 differentially expressed proteins preliminarily, including 279 up-regulated proteins and 79 down-regulated proteins. Thirty-eight differentially expressed secreted proteins involved in the progress of platelet degranulation between TB patients and HCs were focused. Of these, serotransferrin (TRF), alpha-2-macroglobulin (AMG), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein 1 (AAG), alpha-1-acid glycoprotein 2 (AGP2), and alpha-1B-glycoprotein (A1BG) were selected for further verification in the serum of additional 134 TB patients and 138 HCs by nephelometry and ELISA in the training set. Statistically significant differences of TRF (P < 0.0001), AAT (P < 0.0001), AAG (P < 0.0001), AGP2 (P < 0.0001), and A1BG (P = 0.0003) were observed. The serum concentration of TRF was down-regulated in TB patients compared with healthy controls, which was coincident with the proteomics results. An additional validation of TRF was performed in an independent cohort of patients with active TB (n = 46), patients with lung cancer (n = 37), 20 HCs, and patients with pneumonia (n = 35) in the test set by nephelometry. The serum expression levels of TRF in the TB patients showed lower levels compared with those in patients with pneumonia (P = 0.0125), lung cancer (P = 0.0005), HCs (P < 0.0001), and the non-TB controls (P < 0.0001). Furthermore, the AUC value of TRF was 0.647 with 90.22% sensitivity and 42.86% specificity in discriminating the TB group from the pneumonia group, 0.702 with 93.48% sensitivity and 47.16% specificity in discriminating the TB group from the lung cancer group, 0.894 with 91.30% sensitivity and 71.62% specificity in discriminating the TB group from all HCs, and 0.792 with 91.30% sensitivity and 58.90% specificity in discriminating the TB group from the non-TB controls. This study obtained the proteomic profiles of neutrophils in the TB patients and HCs, which contribute to a better understanding of the pathogenesis molecules existing in the neutrophils of pulmonary tuberculosis and provide candidate biomarkers for the diagnosis of pulmonary tuberculosis.

Dataset Information

Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion.

Publications

Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion.

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