The great platelet paradox: evolution of platelet contribution to hemostasis, inflammation, and thrombosis after injury

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Abstract

In the setting of severe injury, a rapid hemostatic response led by platelets at the site of endothelial injury is critical to achieve hemostasis. In a process intricately linked with hemostasis, platelets undertake the role of a sentinel immune cell, sensing and releasing danger-associated molecular pattern proteins (DAMPs) and proinflammatory ligands to conduct the initial inflammatory response. Although this serves as a well-adapted system for hemostasis at the local site of endothelial injury, initiation of this cascade at sites other than a point of active hemorrhage may have deleterious consequences. Severe trauma, including soft tissue injury even in the absence of hemorrhage, is characterized by a systemic surge of DAMPs and activating ligands that results in a series of changes in the morphology and function of the platelet that are linked to thrombotic complications, such as microvascular injury and venous thromboembolism. This talk explores some of the platelet signals and functions unique to the innate immune profile of severe trauma, as well as highlights major knowledge gaps in the field in the setting of an overarching hypothesis of how such a dual role for platelets may have evolved.

Supplementary Material

The complete text of this Blood Advances Talk is available as a data supplement.

Contribution: M.D.N. is the sole author of the article and is the speaker in the audio version of this Blood Advances Talk.

Conflict-of-interest disclosure: M.D.N. is a member of the Scientific Advisory Board for Haima Therapeutics and holds equity stake in the company; receives grant funding from Janssen Pharmaceuticals, Haemonetics, Instrument Laboratories, and Noveome Biotherapeutics; and has received honoraria from Haemonetics and CSL Behring.

Correspondence: Matthew D. Neal, Department of Surgery, University of Pittsburgh, F1271.2 PUH, 200 Lothrop St, Pittsburgh, PA 15213; e-mail: nealm2@upmc.edu.