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CC BY 4.0 · TH Open 2023; 07(01): e42-e55
DOI: 10.1055/a-2000-6576
Original Article

In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia

Søren Nygaard
1   Department of Clinical Biochemistry, Thrombosis and Hemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
,
Christine L. Hvas
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
3   Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
,
Anne-Mette Hvas 
4   Faculty of Health, Aarhus University, Aarhus, Denmark
,
Kasper Adelborg
1   Department of Clinical Biochemistry, Thrombosis and Hemostasis Research Unit, Aarhus University Hospital, Aarhus, Denmark
2   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
5   Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
6   Department of Clinical Biochemistry, Gødstrup Regional Hospital, Herning, Denmark
› Author Affiliations Funding The study was fully supported by the Aarhus University Research Foundation (fund license no.: AU FF-E-2020-7-20).
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Abstract

Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant prophylaxis for this patient population is challenging. We investigated the in vitro effect of low-molecular-weight heparin (dalteparin) and direct thrombin inhibitor (argatroban) on the hemostasis in blood from sepsis patients with new-onset thrombocytopenia. Thrombocytopenia was defined as a platelet count drop of ≥30% and/or from >100 × 109/L to 30 to 100 × 109/L within 24 hours prior to inclusion. We included five healthy individuals and ten patients. Analyses of thrombin generation (Calibrated Automated Thrombogram), thrombin-antithrombin (TAT) complex levels, prothrombin fragment 1+2 (F1+2), and rotational thromboelastometry (ROTEM) were performed. Based on dose–response relationships investigated in healthy blood, patient samples were spiked with prophylactic (0.25 IU/mL) and therapeutic (0.75 IU/mL) dalteparin and low (0.25 µg/mL) and high (0.50 µg/mL) argatroban concentrations, each with a sample without anticoagulant. In patients, the endogenous thrombin potential was markedly lower in therapeutic dalteparin samples than in samples without anticoagulant [median (range): 29 (0–388) vs. 795 (98–2121) nM × min]. In high argatroban concentration samples, thrombin lag time was longer than in samples without anticoagulant [median (range): 15.5 (10.5–20.2) versus 5.3 (2.8–7.3) min]. Dalteparin and argatroban both increased clotting time but did not affect maximum clot firmness in the ROTEM INTEM assay. Six patients had elevated TAT and eight patients had elevated F1 + 2. In conclusion, dalteparin mainly affected the amount of thrombin generated and argatroban delayed clot initiation in critically ill sepsis patients with new-onset thrombocytopenia. Neither anticoagulant affected clot strength.

Keywords

thrombin - intensive care unit - thromboelastometry - anticoagulant prophylaxis - sepsis - thrombocytopenia

Authors' Contributions

The study was conceptualized by K.A. and AM.H. All authors were involved in the design of the study. The screening and inclusion process was made feasible by C.L.H. and performed by S.N. The medical record data extraction, laboratory analyses, statistics, graphics, and data management were performed by S.N. K.A. had the primary responsibility of the study and supervised the process from start to finish. S.N. wrote the first draft of the manuscript, which was reviewed by all authors. All authors approved the manuscript prior to submission.


Supplementary Material



Publication History

Received: 02 September 2022

Accepted: 14 December 2022

Accepted Manuscript online:
18 December 2022

Article published online:
30 January 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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