Beneficial effects of antiplatelet drugs in patients with community-acquired pneumonia and in endotoxin shock in mice
© BioMed Central Ltd. 2007
Published: 22 March 2007
Systemic inflammation and sepsis are associated with blood platelet activation, which may contribute to the development of organ failure. In this study we proved whether antiplatelet drugs have a benefit in patients who may develop sepsis as well as in a mouse model of endotoxin shock.
Data obtained from 224 patients with community-acquired pneumonia (CAP) were retrospectively analysed for an association between prehospital treatment with long-acting antiplatelet drugs such as acetyl salicylic acid (n = 36) or thienopyridine ADP-receptor antagonists (clopidogrel or ticlopidin, n = 8) and clinical outcome. Use of statins was an exclusion criterion. BALB/c mice were pretreated with clopidogrel for 4 days prior to an intraperitoneal injection of LPS (Escherichia coli 0111:B4). For platelet counts and blood gas analysis, standard procedures were used. Lung tissues were stained with HE or a FITC-labelled anti-fibrin(ogen) antibody.
CAP patients with antiplatelet drugs (n = 44) were older than control patients (n = 180; 69 ± 7 vs 58 ± 13 years, P < 0.00001). At the day of hospital admission there were no differences in platelet or leukocyte counts, CRP and SOFA scores between both groups. However, patients on antiplatelet drugs developed organ failure less frequently than control patients (ICU admission: 9.1% vs 26.1%; P < 0.02). In the mouse model of endotoxin shock, clopidogrel reduced the drop in platelet count and the degree of lung injury. Compared with controls we found 20 hours after LPS injection in the clopidogrel-treated animals a lower number of thrombi in the lung vasculature (6.1 ± 2.3 vs 11.5 ± 4.4 thrombi per screen, P < 0.025) as well as higher blood pH and bicarbonate levels (7.01 ± 0.01 vs 6.93 ± 0.04, P < 0.04 and 10.2 ± 0.14 vs 7.3 ± 0.14 mmol/l, P < 0.03, respectively).
Antiplatelet drugs may have a beneficial effect in systemic inflammation and sepsis, and could be a novel therapy option, at least in patients of low bleeding risk. One mechanism of their effects could be a reduction in the microvascular thrombus formation.