Platelet–leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke

Abstract

Stroke is a common and often fatal event, and, in survivors, it is accompanied by a high risk of recurrence. Ischemic stroke is associated with abnormal platelet activity and thrombus formation. In addition to their roles in the development of acute thrombi, platelets serve as a bridge for leukocytes within the vasculature. Myeloid leukocytes are critical mediators of atherosclerosis and atherothrombosis. Interactions between platelets and leukocytes foster an inflammatory and thrombotic milieu that influences lesion progression, facilitates plaque rupture, and triggers thrombus formation and embolization. Accordingly, antiplatelet agents, including aspirin, dipyridamole, and clopidogrel, are recommended therapies for most patients with a history of stroke. In addition to mitigating thrombosis, antiplatelet drugs have direct and indirect effects on inflammation, which may translate to enhanced clinical efficacy.

Platelet-to-White Blood Cell Ratio: A Prognostic Predictor for 90-Day Outcomes in Ischemic Stroke Patients with Intravenous Thrombolysis

“…45 Activated platelets also release a variety of prothrombotic and proinflammatory mediators associated with leukocyte recruitment, including soluble CD40 ligand, regulated upon activation, normal T cell expressed and secreted (RANTES), and thromboxane A2. 21 Moreover, the formation of LPA may contribute to ischemia-reperfusion injury, 23,24 which may be associated with the therapeutic effect of IVT. Kupatt et al 46 have proposed that LPAs have the properties to exaggerate reperfusion injury by accumulating in blood vessels with an ischemic event, and Ritter et al 24 have found an approximately 2-fold increase in LPA after ischemic stroke and reperfusion compared to preischemic values, leading to microvascular plugging and decreased ischemia perfusion.…”

“…23,24 Platelet-leukocyte interactions have been increasingly elucidated to be associated with inflammation and onset of ischemic events. 21,44 Leukocyte-platelet aggregates (LPAs) in peripheral blood have been considered as a novel marker of activated platelets, 15 which possess the "bridge" effects for other cells in vasculature, particularly leukocytes recruited via platelet secretory components including several chemokines and membrane ligands. 21 The interplay of platelets and leukocytes is primarily attributed to P-selectin, an adhesive molecule reserved in platelet alpha-granules and transported to the surface of activated platelets.…”

“…21,44 Leukocyte-platelet aggregates (LPAs) in peripheral blood have been considered as a novel marker of activated platelets, 15 which possess the "bridge" effects for other cells in vasculature, particularly leukocytes recruited via platelet secretory components including several chemokines and membrane ligands. 21 The interplay of platelets and leukocytes is primarily attributed to P-selectin, an adhesive molecule reserved in platelet alpha-granules and transported to the surface of activated platelets. The pivotal receptor for P-selectin, P-selectin glycoprotein ligand-1, is elementarily expressed on the membranes of most leukocytes.…”

“…16,17 Elevated peripheral total leukocyte and neutrophil counts are also associated with stroke severity on admission, 18 a higher recurrence of ischemic stroke, 19 and even poorer functional outcome. 20 Recent studies have also elaborated on the interactions between platelets with leukocytes in ischemic stroke 21 and acute coronary syndrome. 22 This interplay has been elucidated to be correlated with ischemiareperfusion injury.…”

Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion

“…A number of clinical reports demonstrate that trauma, including burn injury and I/R injury, leads to platelet dysregulation (26,27,32,42,44,53,66,69,81). While there is ample evidence demonstrating a functional role for platelets in ischemic stroke (30,49,54,64,65), there is little published evidence supporting a pathological role for platelets in local and remote tissue damage after I/R injury.…”