Antiplatelet Therapy for Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a common and devastating syndrome that contributes to serious morbidities and mortality in critically ill patients. No known pharmacologic therapy is beneficial in the treatment of ARDS, and the only effective management is through a protective lung strategy. Platelets play a crucial role in the pathogenesis of ARDS, and antiplatelet therapy may be a potential medication for ARDS. In this review, we introduce the overall pathogenesis of ARDS, and then focus on platelet-related mechanisms underlying the development of ARDS, including platelet adhesion to the injured vessel wall, platelet-leukocyte-endothelium interactions, platelet-related lipid mediators, and neutrophil extracellular traps. We further summarize antiplatelet therapy, including aspirin, glycoprotein IIb/IIIa receptor antagonists, and P2Y12 inhibitors for ARDS in experimental and clinical studies and a meta-analysis. Novel aspirin-derived agents, aspirin-triggered lipoxin, and aspirin-triggered resolvin D1 are also described here. In this narrative review, we summarize the current knowledge of the role of platelets in the pathogenesis of ARDS, and the potential benefits of antiplatelet therapy for the prevention and treatment of ARDS.

Keywords: acute respiratory distress syndrome; antiplatelet; aspirin; therapy.

Figure 1

The pathological features of acute respiratory distress syndrome (ARDS) in the acute phase. In the air space, alveolar macrophages secrete cytokines locally to stimulate chemotaxis and activate neutrophils. Neutrophils can release oxidants, proteases, leukotrienes, and other pro-inflammatory molecules, such as platelet-activating factor (PAF). PAF: platelet-activating factor; IL: interleukin; TNF: tumor necrosis factor; LTs: leukotriene.

Figure 2

The role of platelets in acute respiratory distress syndrome. Platelets have an increasingly recognized role in the inflammatory response leading to the development of ARDS. The possible mechanisms by which platelets contribute to ARDS include the activation of endothelial cells by the release of pro-inflammatory mediators and adherence of platelets to lung capillary endothelial cells leading to activation of attached leukocytes.

Figure 3

The role of specific adhesion molecules in the platelet-neutrophil interaction, adhesion to endothelium, and platelet aggregation. Triggering receptor expressed on myeloid cells (TREM)-like transcript-1: TLT-1; intercellular adhesion molecule-1: ICAM-1; P-selectin glycoprotein ligand 1: PSGL-1; glycoprotein: GP; Platelet and endothelial cell adhesion molecule-1: PECAM-1.

Figure 4

Protective effects of aspirin against lung inflammation. Neutrophil recruitment to the sites of lung injury may also be modulated through aspirin-triggered anti-inflammatory mediators.