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

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...

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Autores principales: Nygaard, Søren, Hvas, Christine L., Hvas, Anne-Mette, Adelborg, Kasper
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Georg Thieme Verlag KG 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886503/
https://www.ncbi.nlm.nih.gov/pubmed/36751302
http://dx.doi.org/10.1055/a-2000-6576
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author Nygaard, Søren
Hvas, Christine L.
Hvas, Anne-Mette
Adelborg, Kasper
author_facet Nygaard, Søren
Hvas, Christine L.
Hvas, Anne-Mette
Adelborg, Kasper
author_sort Nygaard, Søren
collection PubMed
description 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 × 10 (9) /L to 30 to 100 × 10 (9) /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.
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spelling pubmed-98865032023-02-06 In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia Nygaard, Søren Hvas, Christine L. Hvas, Anne-Mette Adelborg, Kasper TH Open 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 × 10 (9) /L to 30 to 100 × 10 (9) /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. Georg Thieme Verlag KG 2023-01-30 /pmc/articles/PMC9886503/ /pubmed/36751302 http://dx.doi.org/10.1055/a-2000-6576 Text en 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/ ) https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Nygaard, Søren
Hvas, Christine L.
Hvas, Anne-Mette
Adelborg, Kasper
In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia
title In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia
title_full In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia
title_fullStr In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia
title_full_unstemmed In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia
title_short In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia
title_sort in vitro effect of dalteparin and argatroban on hemostasis in critically ill sepsis patients with new-onset thrombocytopenia
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886503/
https://www.ncbi.nlm.nih.gov/pubmed/36751302
http://dx.doi.org/10.1055/a-2000-6576
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