Gram-Negative Pneumonia Alters Large-Vein Cell-Adhesion Molecule Profile and Potentiates Experimental Stasis Venous Thrombosis

Abstract

Background/Aims: Pneumonia is a significant risk factor for the development of venous thrombosis (VT). Cell-adhesion molecules (CAMs) are linked to the pathogenesis of both pneumonia and VT. We hypothesized that remote infection would confer a prothrombogenic milieu via systemic elevation of CAMs. Methods: Lung injury was induced in wild-type (C57BL/6) mice by lung contusion or intratracheal inoculation with Klebsiella pneumoniae or saline controls. K. pneumoniae-treated mice and controls additionally underwent inferior vena cava (IVC) ligation to generate VT. Results: Lung-contusion mice demonstrated no increase in E-selectin or P-selectin whereas mice infected with K. pneumoniae demonstrated increased circulating P-selectin, ICAM-1, VCAM-1 and thrombin-antithrombin (TAT) complexes. Mice with pneumonia formed VT 3 times larger than controls, demonstrated significantly more upregulation of vein-wall and systemic CAMs, and formed erythrocyte-rich thrombi. Conclusion: Elevated CAM expression was identified in mice with pneumonia, but not lung contusion, indicating that the type of inflammatory stimulus and the presence of infection drive the vein-wall response. Elevation of CAMs was associated with amplified VT and may represent an alternate mechanism by which to target the prevention of VT.

The association of venous thromboembolism chemoprophylaxis timing on venous thromboembolism after major vascular surgery

“…Previous population and registry studies have identified a link between pneumonia and VTE. 27–30 This may be due in part to inflammatory and/or infectious stimuli effect on the venous endothelium or simply a reflection of these patients immobility and frailty. Scarborough et al identified VTE events in conjunction with the timing of post-operative complications and found that 5.6% of patients who developed pneumonia subsequently developed a VTE.…”

TLR3 absence confers increased survival with improved macrophage activity against pneumonia

“…For blood CFU determinations, blood was collected via cardiac puncture using a sterile 18-gauge needle. To measure bacterial number, 100 μL of undiluted blood was plated onto 5% sheep blood agar plates (Thermo Fisher Scientific) and incubated at 37°C, and then colonies were counted (4,5,49).…”

P‐ and E‐ selectin in venous thrombosis and non‐venous pathologies

“…In another study using the model of complete IVC stasis, when mice were inoculated with klebsiella pneumoniae to induce pneumonia, they were found to have increased levels of circulating P-selectin. 25 Since elevated sP-selectin is associated with DVT risk and sepsis increases risk for VTE, the role of P-selectin in sepsis associated DVT was explored. When sepsis was induced experimentally in mice with the endotoxin lipopolysaccharide, Pselectin was up-regulated at the vein wall.…”

“…The fact that similar findings have been found in these different models is important, as areas of complete stasis and partial stasis often exist simultaneously in the pathophysiology of clinical DVT. In another study using the model of complete IVC stasis, when mice were inoculated with klebsiella pneumoniae to induce pneumonia, they were found to have increased levels of circulating P‐selectin 25 . Since elevated sP‐selectin is associated with DVT risk and sepsis increases risk for VTE, the role of P‐selectin in sepsis associated DVT was explored.…”