Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood

Background: Platelets are highly sensitive to subtle changes in their microenvironment, making functional analyses challenging and prone to variation. Advances in understanding how experimental procedures influence human platelet activation have improved the accuracy and comparability of diagnostic...

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Main Authors: Silvia Maria Grazia Trivigno, Alice Assinger, Waltraud Cornelia Schrottmaier
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037925002079
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author Silvia Maria Grazia Trivigno
Alice Assinger
Waltraud Cornelia Schrottmaier
author_facet Silvia Maria Grazia Trivigno
Alice Assinger
Waltraud Cornelia Schrottmaier
author_sort Silvia Maria Grazia Trivigno
collection DOAJ
description Background: Platelets are highly sensitive to subtle changes in their microenvironment, making functional analyses challenging and prone to variation. Advances in understanding how experimental procedures influence human platelet activation have improved the accuracy and comparability of diagnostic and research data. However, despite the pivotal role of murine models, the effects of methodological variations on murine platelets remain incompletely understood. Objectives: To elucidate how blood draw techniques, anticoagulation, processing delay, and assay temperature affect murine platelets. Methods: Blood was obtained by retro-orbital, vena cava, or cardiac puncture and anticoagulated with heparin, citrate, or acid-citrate-dextrose ± recalcification. After 30 to 120 minutes, blood was stimulated at room temperature or 37 °C with adenosine diphosphate (ADP), protease-activated receptor 4-activating peptide (PAR4-AP), or cross-linked collagen-related peptide (CRP-XL), and platelets were analyzed by flow cytometry for CD62P, CD63, CD40L, and activated glycoprotein IIb/IIIa. Results: Blood sampling had minimal impact on ADP-induced platelet activation. However, platelets isolated via vena cava or cardiac puncture exhibited heightened responsiveness to PAR4-AP and CRP-XL, respectively, compared with retro-orbital sampling. Citrate and acid-citrate-dextrose significantly impaired PAR4-AP responses compared with heparin, whereas CRP-XL sensitivity was anticoagulant-independent. Processing delays as brief as 60 minutes significantly altered platelet reactivity to CRP-XL and PAR4-AP, with further delays producing minimal additional impact. Finally, ADP- and CRP-XL–induced platelet activation was significantly reduced at 37 °C compared with room temperature. Conclusion: Common variations in murine platelet handling influence in vitro responsiveness of platelets in an agonist-specific manner, highlighting the critical need for meticulous assay optimization to ensure experimental consistency and comparability.
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spelling doaj-art-9220ad266041427c907e25a6aa2a022c2025-08-20T03:04:46ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-05-019410288310.1016/j.rpth.2025.102883Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole bloodSilvia Maria Grazia Trivigno0Alice Assinger1Waltraud Cornelia Schrottmaier2Institute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria; University School for Advanced Studies, Istituto Universitario di Studi Superiori (IUSS), Pavia, Italy; Department of Biology and Biotechnology, University of Pavia, Pavia, ItalyInstitute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria; Correspondence Waltraud Cornelia Schrottmaier and Alice Assinger, Centre of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.Institute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria; Correspondence Waltraud Cornelia Schrottmaier and Alice Assinger, Centre of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.Background: Platelets are highly sensitive to subtle changes in their microenvironment, making functional analyses challenging and prone to variation. Advances in understanding how experimental procedures influence human platelet activation have improved the accuracy and comparability of diagnostic and research data. However, despite the pivotal role of murine models, the effects of methodological variations on murine platelets remain incompletely understood. Objectives: To elucidate how blood draw techniques, anticoagulation, processing delay, and assay temperature affect murine platelets. Methods: Blood was obtained by retro-orbital, vena cava, or cardiac puncture and anticoagulated with heparin, citrate, or acid-citrate-dextrose ± recalcification. After 30 to 120 minutes, blood was stimulated at room temperature or 37 °C with adenosine diphosphate (ADP), protease-activated receptor 4-activating peptide (PAR4-AP), or cross-linked collagen-related peptide (CRP-XL), and platelets were analyzed by flow cytometry for CD62P, CD63, CD40L, and activated glycoprotein IIb/IIIa. Results: Blood sampling had minimal impact on ADP-induced platelet activation. However, platelets isolated via vena cava or cardiac puncture exhibited heightened responsiveness to PAR4-AP and CRP-XL, respectively, compared with retro-orbital sampling. Citrate and acid-citrate-dextrose significantly impaired PAR4-AP responses compared with heparin, whereas CRP-XL sensitivity was anticoagulant-independent. Processing delays as brief as 60 minutes significantly altered platelet reactivity to CRP-XL and PAR4-AP, with further delays producing minimal additional impact. Finally, ADP- and CRP-XL–induced platelet activation was significantly reduced at 37 °C compared with room temperature. Conclusion: Common variations in murine platelet handling influence in vitro responsiveness of platelets in an agonist-specific manner, highlighting the critical need for meticulous assay optimization to ensure experimental consistency and comparability.http://www.sciencedirect.com/science/article/pii/S2475037925002079animal experimentationanticoagulantblood specimen collectiondelayed processingmethod optimizationplatelet activation
spellingShingle Silvia Maria Grazia Trivigno
Alice Assinger
Waltraud Cornelia Schrottmaier
Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood
Research and Practice in Thrombosis and Haemostasis
animal experimentation
anticoagulant
blood specimen collection
delayed processing
method optimization
platelet activation
title Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood
title_full Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood
title_fullStr Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood
title_full_unstemmed Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood
title_short Impact of sampling technique, anticoagulant, processing delay, and temperature on murine platelet function in whole blood
title_sort impact of sampling technique anticoagulant processing delay and temperature on murine platelet function in whole blood
topic animal experimentation
anticoagulant
blood specimen collection
delayed processing
method optimization
platelet activation
url http://www.sciencedirect.com/science/article/pii/S2475037925002079
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AT aliceassinger impactofsamplingtechniqueanticoagulantprocessingdelayandtemperatureonmurineplateletfunctioninwholeblood
AT waltraudcorneliaschrottmaier impactofsamplingtechniqueanticoagulantprocessingdelayandtemperatureonmurineplateletfunctioninwholeblood