Anti-platelet drugs and outcome in severe infection: Clinical impact and underlying mechanisms

Abstract

Platelet activation contributes to microvascular thrombosis and organ failure in systemic inflammation. We tested the hypothesis whether anti-platelet drugs might favourably affect outcome in patients at risk for organ failure as well as in a mouse model of endotoxin shock. Two hundred twenty-four consecutive patients who were admitted for community acquired pneumonia over a time period of 5 years to a University Hospital were enrolled; about 20% of whom received anti-platelet drugs (acetylsalicylic acid, thienopyridines) for secondary prevention of cardiovascular disease. Patients with anti-platelet drugs were about 12 years old but did not differ in SOFA score and routine laboratory parameters at admission. Logistic regression and 2 x 2 table analysis in age-matched subgroups indicated that anti-platelet drugs may reduce the need of intensive care treatment (odds ratio (OR) 0.32 [95% confidential interval: 0.10-1.00] and 0.19 [0.04-0.87], respectively). In age-matched subgroups, the use of anti-platelet drugs was also associated with a shorter stay in hospital (13.9 +/- 6.2 vs. 18.2 +/- 10.2 days; p < 0.02). In the animal model Balb/c mice were pre-treated with clopidogrel (added to drinking water) for 4 days prior to intraperitoneal (i.p.) administration of endotoxin (lipopolsaccharide (LPS) from Escherichia coli 0111:B4). Within the first 48 hours after LPS there were no differences between clopidogrel and control animals (n = 26 each) in macro-haemodynamics. However, clopidogrel abolished the LPS-induced drop in platelet count and reduced fibrin deposition in lung tissue. Using DNA microarray technology, we could show that clopidogrel suppressed endotoxin-induced up-regulation of inflammation-relevant genes, including arachidonate-5-lipoxygenase activating protein and leukotriene B4 receptor 1. According to our data a possible benefit of anti-platelet drugs in patients on risk for systemic inflammation and organ failure should be tested in a prospective trial.

Cardiac Complications in Patients With Community-Acquired Pneumonia

“…Such interventions should stem from a better understanding of the mechanisms involved in the occurrence of these events in CAP patients. Drugs with known beneficial cardiovascular effects such statins and aspirin, recently linked to improved outcomes in patients with CAP, 32,33 should be looked at more exhaustively in relation to their possible effects in preventing the occurrence on incident cardiac complications in this population. The development of tools for optimal identification of patients with CAP at risk for cardiac events should greatly facilitate these processes.…”

Treatment of comorbid chronic obstructive pulmonary disease and cardiovascular disease

“…Однако при отсутствии указанных призна ков препарат все же может назначаться больным с коморбидной патологией ХОБЛ и ИБС в мини мально эффективных антиагрегантных дозах (75 мг) под контролем самочувствия и функции внешнего дыхания. Более того, по результатам ряда исследова ний показано [40,41], что прием АСК у больных ХОБЛ ассоциировался со снижением смертности и времени пребывания в стационаре.…”

Group G streptococci mediate fibrinogen-dependent platelet aggregation leading to transient entrapment in platelet aggregates

“…Bacteria isolated from patients presenting with Gram-positive bacteraemia can activate platelets from the infected individual, ex vivo, indicating that bacteria-mediated platelet activation may occur during bloodstream infection and sepsis (Johansson et al, 2011). Furthermore, platelets may play a significant role in the pathogenesis and prognosis of sepsis (Levi, 2005;Winning et al, 2009;Sharron et al, 2012). Therefore, in this study we investigated the interaction between platelets and GGS, with particular emphasis on the role of the fibrinogen-and IgG-binding surface proteins, FOG and protein G. Platelet aggregation and disaggregation in response to GGS were described in vitro in healthy human donors.…”

“…Platelets have been reported to contribute to the pathogenesis of GAS infection in an animal model (Kahn et al, 2013); however, platelets have also been proposed to protect in an animal model of sepsis (de Stoppelaar et al, 2014;Xiang et al, 2013). Interestingly, studies of human sepsis patients indicate that antiplatelet therapy is beneficial for the outcome of invasive infection (Winning et al, 2009;Otto et al, 2013;Akinosoglou & Alexopoulos, 2014). Sepsis is a complex clinical syndrome and antiplatelet therapy may only be relevant at a particular stage of sepsis or for sepsis caused by specific bacterial pathogens; therefore, robust investigations are required to assess this possibility.…”