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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 57, Issue 11


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

Gian Luca Salvagno / Emmanuel J. Favaloro
  • Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Davide Demonte / Matteo Gelati / Giovanni Poli / Giovanni Targher
  • Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Verona, Verona, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Giuseppe Lippi
Published Online: 2019-04-02 | DOI: https://doi.org/10.1515/cclm-2019-0135



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.


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).


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.


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

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


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About the article

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

Received: 2019-02-05

Accepted: 2019-03-05

Published Online: 2019-04-02

Published in Print: 2019-10-25

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.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 11, Pages 1784–1789, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0135.

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Giuseppe Lippi and Mario Plebani
Clinical Chemistry and Laboratory Medicine (CCLM), 2019, Volume 57, Number 11, Page 1647

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