Martin Ponschab1, Martijn van Griensven2, Stefan Heitmeier3, Volker Laux4, Christoph J Schlimp5, Andreas Calatzis6, Soheyl Bahrami7, Heinz Redl8, Herbert Schöchl9. 1. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria; Department of Anaesthesiology and Intensive Care, AUVA Trauma Hospital Linz, Academic Teaching Hospital of the Paracelsus Medical University, Salzburg, Austria. Electronic address: martin.ponschab@auva.at. 2. Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Germany. Electronic address: Martijn.vanGriensven@tum.de. 3. Bayer Pharma AG, Acute Care Research, Wuppertal, Germany. Electronic address: stefan.heitmeier@bayer.com. 4. Bayer Pharma AG, Acute Care Research, Wuppertal, Germany. Electronic address: volker.laux@bayer.com. 5. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria. Electronic address: christoph.schlimp@trauma.lbg.ac.at. 6. Verum Diagnostics, Munich, Germany. Electronic address: andreas.calatzis@roche.com. 7. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria. Electronic address: soheyl.bahrami@trauma.lbg.ac.at. 8. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria. Electronic address: heinz.redl@trauma.lbg.ac.at. 9. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria; Department of Anaesthesiology and Intensive Care, AUVA Trauma Centre, Salzburg, Austria. Electronic address: herbert.schoechl@auva.at.
Abstract
BACKGROUND: Platelets play a pivotal role in coagulation, inflammation and wound healing. Suitable animal models that have the potential to mimic human platelet function are limited. The objective of the current study was to compare platelet aggregation response in the whole blood of baboons and humans using impedance aggregometry. METHODS: Blood was drawn from 24 anesthetised male baboons and 25 healthy volunteers. The platelet aggregation response was determined by impedance aggregometry (Multiplate®). Platelets in the hirudinised whole blood samples were stimulated with four different activators: adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating peptide-6 (TR1AP), and activation of PAR-4 thrombin receptor subtype (TR4AP) at standard concentrations. Higher than standard concentrations were tested in a subgroup of the animals. RESULTS: The cell counts showed no differences between baboons and humans. The platelet aggregation response was significantly lower in baboons compared to humans when stimulated with the platelet agonists ADP (p<0.0001), COL (p=0.021) and TR4AP (p<0.0001). TR1AP did not stimulate platelet aggregation in the baboon blood. Doubling the concentration of ADP and of TR4AP significantly increased the AUC compared to the standard concentration. In contrast, increased COL levels did not further increase the AUC. CONCLUSION: The current study revealed that testing the platelet function in baboon blood by impedance aggregometry is feasible with ADP, COL and TR4AP, but not with TR1AP. Compared to humans, the aggregation response is lower in baboons. Considering the limitations in accordance to these results, baboons might represent a potential species for further platelet research.
BACKGROUND: Platelets play a pivotal role in coagulation, inflammation and wound healing. Suitable animal models that have the potential to mimic human platelet function are limited. The objective of the current study was to compare platelet aggregation response in the whole blood of baboons and humans using impedance aggregometry. METHODS: Blood was drawn from 24 anesthetised male baboons and 25 healthy volunteers. The platelet aggregation response was determined by impedance aggregometry (Multiplate®). Platelets in the hirudinised whole blood samples were stimulated with four different activators: adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating peptide-6 (TR1AP), and activation of PAR-4 thrombin receptor subtype (TR4AP) at standard concentrations. Higher than standard concentrations were tested in a subgroup of the animals. RESULTS: The cell counts showed no differences between baboons and humans. The platelet aggregation response was significantly lower in baboons compared to humans when stimulated with the platelet agonists ADP (p<0.0001), COL (p=0.021) and TR4AP (p<0.0001). TR1AP did not stimulate platelet aggregation in the baboon blood. Doubling the concentration of ADP and of TR4AP significantly increased the AUC compared to the standard concentration. In contrast, increased COL levels did not further increase the AUC. CONCLUSION: The current study revealed that testing the platelet function in baboon blood by impedance aggregometry is feasible with ADP, COL and TR4AP, but not with TR1AP. Compared to humans, the aggregation response is lower in baboons. Considering the limitations in accordance to these results, baboons might represent a potential species for further platelet research.