Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma

Gian Luca Salvagno; Emmanuel J. Favaloro; Davide Demonte; Matteo Gelati; Giovanni Poli; Giovanni Targher; Giuseppe Lippi

doi:10.1515/cclm-2019-0135

Article

Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma

Gian Luca Salvagno , Emmanuel J. Favaloro , Davide Demonte , Matteo Gelati , Giovanni Poli , Giovanni Targher and Giuseppe Lippi

Published/Copyright: April 2, 2019

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 11

Abstract

Background

Although accumulating evidence suggests that the hemostatic balance is impaired in patients with hypertriglyceridemia, hyperbilirubinemia or hemolytic anemias, little is known on the underlying biological mechanisms. This experimental study was aimed at exploring whether increasing values of triglycerides, bilirubin or cell-free hemoglobin promote thrombin generation in plasma.

Methods

Three different pools were prepared from three different sets of 20 normal routine plasma citrate samples. The native pools were spiked with increasing amounts of exogenous triglycerides (up to 8.8 mmol/L), bilirubin (up to 350 μmol/L) or autologous hemolyzed blood (up to 3.5 g/L cell-free hemoglobin). Using the fully-automated thrombin generation analyzer ST Genesia, we measured the following parameters: lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP).

Results

A sustained increase of PH and ETP was found in parallel with increasing triglyceride concentrations, peaking in the aliquot with 8.8 mmol/L. Conversely, LT and TP displayed an opposite trend, reaching a maximum decrease in the 8.8 mmol/L aliquot. Increasing bilirubin concentrations promoted remarkable increases of PH and ETP and decreases of TP and LT, up to 211 μmol/L. After this threshold, all parameters tended to return towards baseline values. A constant increase of PH and ETP was also noted in hemolyzed samples, peaking in the 3.5 g/L cell-free hemoglobin aliquot, whereas the TP and LT remained unchanged in all hemolyzed aliquots.

Conclusions

Our findings suggest that hypertriglyceridemia, hyperbilirubinemia and hemolysis may promote a hypercoagulable state in human plasma.

Keywords: bilirubin; hemolysis; thrombin generation; thrombosis; triglycerides

Corresponding author: Prof. Giuseppe Lippi, Section of Clinical Biochemistry, University of Verona, University Hospital of Verona, Piazzale LA Scuro, 37134 Verona, Italy

Acknowledgments

The manufacturer provided in-kind support in the form of equipment and consumables to enable study performance. The manufacturer had no role in directing the study or influencing the interpretation of the study results.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2019-02-05

Accepted: 2019-03-05

Published Online: 2019-04-02

Published in Print: 2019-10-25

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Articles in the same Issue

https://doi.org/10.1515/cclm-2019-0135

Keywords for this article

bilirubin; hemolysis; thrombin generation; thrombosis; triglycerides