Platelet dysfunction has been identified as an important contributor of trauma-induced coagulopathy, but the underlying mechanism still remains to be elucidated. Trauma-associated proinflammatory stimuli strongly activate leukocytes, which in turn bind activated platelets. Therefore, we investigated the role of platelet-leukocyte aggregation (PLA) as a potential feature of trauma-induced platelet dysfunction.
Whole blood from 10 healthy donors was exposed to selective and collective platelet and leukocyte agonists in order to simulate differential states of activation. PLA formation and CD11b expression as a measure of leukocyte activation were determined by flow cytometry. Platelet-mediated hemostatic function was measured by thromboelastometry (ROTEM) and impedance aggregometry (Multiplate).
Activation of platelets and leukocytes was associated with diminished platelet-mediated hemostatic potential. Aggregation of platelets with monocytes rather than granulocytes resulted in a reduction of hemostatic function, as indicated by an impaired responsiveness in platelet aggregometry and a reduction of thromboelastometric maximum clot firmness. This finding was irrespective of CD11b expression and was not paralleled by a reduction of measurable platelet counts.
PLA formation occurs primarily between monocytes and activated platelets and is associated with impaired platelet-mediated hemostatic function. PLA formation was not paralleled by a reduction in platelet complete blood counts.
From the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology (J.Z., K.A., M.P., C.J.S., S.B., H.R., H.S.), AUVA Research Centre, Vienna; Department of Anaesthesiology and Intensive Care (M.P.), AUVA Trauma Centre, Linz, Austria; Department of Anaesthesia, Critical Care and Pain Medicine (C.J.S.), Royal Infirmary of Edinburgh, Scotland, United Kingdom; Core Facility Flow Cytometry and Surgical Research Laboratories (A.S.), Medical University of Vienna, Vienna, Austria; and Department of Anaesthesiology and Intensive Care (H.S.), AUVA Trauma Centre Salzburg, Academic Teaching Hospital of the Paracelsus Medical University, Salzburg, Austria.
Submitted: November 9, 2016, Revised: December 20, 2016, Accepted: January 18, 2017, Published online: March 2, 2017.
Address for reprints: Herbert Schöchl, MD, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Donaueschingenstrasse 13, 1200 Vienna, Austria; email: firstname.lastname@example.org.