Platelets

Abstract

Platelets are anucleate and subcellular fragments of megakaryocytes that are biologically active and essential to coordinated coagulation, vascular integrity, and immune function. However, despite these pivotal roles of platelets, it was not until Hoffman and Monroe’s “cell-based model of hemostasis” (Hoffman and Monroe, Thromb Haemost 85(6):958–965, 2001) that investigators turned significant focus on the role of platelet biology in trauma-induced coagulopathy (TIC). Since then, a large body of investigation has focused on elucidating post-injury platelet biology as part of understanding the multidimensional TIC that encompasses various phenotypes of clot formation and lysis, vascular homeostasis, and immunoregulation associated with pathologies of bleeding, clotting, organ failure, and death after injury (Chang et al., Blood 128(8):1043–1049, 2016; Kornblith et al., J Thromb Haemost JTH 17(6):852–862, 2019; Verni et al., J Trauma Acute Care Surg 86(2):250–259, 2019; Moore et al., J Am Coll Surg 222(4):347–355, 2016; J Trauma Acute Care Surg 77(6):811–817, 2014; McGhan and Jaroszewski, Injury 43(2):129–136, 2012; Ding et al., Circ Cardiovasc Genet 7(5):615–624, 2014). Although it has long been evidenced that post-injury thrombocytopenia is associated with bleeding, progression of brain injury, and mortality (Brown and Call, J Trauma 2011;71(2 Suppl 3):S337-S342; Schnüriger et al., J Trauma Inj Infect Crit Care 68(4):881–885, 2010), multiple studies have now demonstrated that injured patients also demonstrate impaired platelet aggregation in in vitro aggregometry assays, despite having normal platelet counts (Jacoby et al., J Trauma 51(4):639–647, 2001; Kutcher et al., J Trauma Acute Care Surg 73(1):13–19, 2012; Li et al., J Trauma Acute Care Surg 80(3):440, 2016; Solomon et al., Thromb Haemost 106(08):322–330, 2011). Specific to this, this chapter will review (1) platelet biology in TIC, including discussions of thrombocytopenia, platelet activation, platelet aggregation, platelet-regulated endothelial integrity, platelet-regulated fibrinolysis, and platelet-regulated immunoactivation, (2) limitations of measuring platelet biology in TIC, (3) platelet transfusions in TIC, and (4) conclusions and future directions. In addition, this chapter intends to highlight the controversies specific to whether alterations in platelet biology after injury are physiologic or maladaptive, diagnostic issues related to the measurement of platelet biology in the trauma patient, and current uncertainties regarding the role of platelet-based treatments for hemorrhaging trauma patients.