Use of antiplatelet agents in sepsis: a glimpse into the future

Abstract

As mechanisms of sepsis pathophysiology have been elucidated with time, sepsis may be considered nowadays, as an uncontrolled inflammatory and pro-coagulant response to a pathogen. In this cascade of events, platelets play a key role, via interaction with endothelial cells and modulation of both innate and adaptive immune system. In that manner, inhibition of platelet function could represent a useful tool for attenuating inflammatory response and improving outcomes. Data on current antiplatelet agents, including acetylsalicylic acid, P2Y12 inhibitors and GPIIb/IIIa antagonists, in animal models are promising. Clinical data in patients hospitalized for pneumonia, at risk for acute lung injury, and/or critically ill revealed an association between antiplatelet therapy and reduction in both short-term mortality and prevalence of acute lung injury, as well as, the need for intensive care unit admission, without a concomitant increased bleeding risk. In need of innovative approach in the treatment of sepsis, further prospective, interventional, randomized trials are pivotal to establish potential use of antiplatelet agents in this context.

Keywords: 15-epi-lipoxin A4; A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13; ADAMTS-13; ADP; ALI; ARDS; ASA; ATL; ATP; AcetylSaliculic Acid; Acute Lung Injury; Acute Respiratory Distress Syndrome; Adenosine Diphosphate; Adenosine Triphosphate; Antiplatelet agents; C-Reactive Protein; C4b; CABG; CAP; COX; CRP; Community Acquired Pneumonia; Coronary Artery Bypass Grafting; CyclOXygenase; DIC; Disseminated Intravascular Coagulation; Erk1; GP; GPIIb/IIIa antagonists; GlycoProtein; ICU; IL-#; IL-10r; Intensive Care Unit; InterLeukine #; InterLeukine 10 receptor; LPS; LeukoTriene b4 Receptor; LipoPolySacccharide; Ltb4r; MIP-1a; MOF; Macrophage inflammatory protein-1alpha; Multiple Organ Failure; NET; NFκB; NO; Neutrophil Extracellular Trap; Nitrogen Oxide; P-Selectin Glycoprotein Ligand-1; P2Y12 inhibitors; PAF; PLATO; PLATelet inhibition and clinical Outcomes; PMN; PSGL-1; Platelet Activating Factor; Platelets; PolyMorphoNuclear cells; RANTES; ROS; Reactive Oxygen Species; Regulated on Activation, Normal T cell Expressed and Secreted; SIRS; Sepsis; Systemic Inflammatory Response Syndrome; T-Cell Receptor; TCR; TF; TLR; TNF alpha; Tissue Factor; Toll-Like Receptor; Tumor Necrosis Factor alpha; complement component 4b; eNOs; endogenous nitric oxide synthase; extra cellular signal kinase 1; iNOs; inducible nitric oxide synthase; nuclear factor kappa-light-chain-enhancer of activated B cells; vWF; von Willebrand Factor.