| dc.description.abstract | Acute inflammation in response to severe bacterial infection, results in
hemostatic abnormalities ranging from subclinical to sustained systemic
clotting activation leading to massive thrombin and fibrin formation and
microvascular thrombosis. Endothelial activation and dysfunction are critical
determinants of the host response and provide an explanation for the
different abnormalities involved in the pathophysiology of sepsis.
Infection with pathogenic E. coli may present with a wide spectrum of clinical
manifestations, from no symptoms or mild non-bloody diarrhea to severe
cases, such as hemolytic uremic syndrome or thrombotic thrombocytopenic
purpura, which is characterized by hemolytic anemia and low platelet counts.
Although the understanding of the mechanisms that are involved in blood
coagulation abnormalities in sepsis has gradually progressed, the role of
platelets (Plts) on the procoagulant state during a severe infection remains to
be addressed. Human platelets contain functional tissue factor (TF) (Panes et
al. 2007) and TFPIa, but it is unknown if bacteria-platelet interaction affects
platelet-TF procoagulant or platelet TFPI anticoagulant activities. Moreover,
the effects of bacterial activation of platelets on thrombin generation (TG) in
platelet rich plasma (PRP) or adhesion to endothelial cells have not been
explored.
Aims: We assessed the effect of platelet-E. coli interaction on platelet TFdependent
procoagulant activity (PCA), the changes induced by this
interaction on platelet TFPI, in TG in PRP and in the adhesive capacity of
platelets on cultured HUVEC.
December 06, 2014 Table of Contents
Previous
Related Articles -
No related articles found.
Email
Citation Alert
Correction Alert
Citation Tools
Save to My Folders
© Request Permissions
Share
Article
Info & Metrics
E-Letters
Home / December 6, 2014; Blood: 124 (21)
Current Issue First Edition Collections All Issues Abstracts Video Library
Home About Blood Authors Submit to Blood Subscriptions Classifieds
ASH Home Blood App My Folders Alerts RSS Institution: PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE Sign In
Plts activation by E. coli was demonstrated by a significant increase of pselectin
exposure on platelet surface compared to control Plts after 30 min of
interaction with this microorganism harvested at exponential phase of growth
and incubated in a ratio Plts/bacteria 1:10.
Platelet TF-dependent PCA was assessed by FXa generation in washed Plts
exposed to E. coli, with addition of exogenous FVIIa and FX, with no extra
source of TF. Using the same ratio Plts/bacteria, we observed an increase in
FXa after 30 min of incubation, compared with control platelets (p=0.0002,
n=12). This enhancement in TF-PCA was concomitant with a decreased
expression of TFPI in Plts surface after exposure of PRP to E. coli for 30 min.
(p=0.0012, n=9).
TG was measured in PRP, previously stimulated by E. coli for 30 min. We
observed a shortening in the Lag time and time to peak and a higher
thrombin peak in stimulated than in control PRP (p=0.0001, p=0.005 and
p=0.0342, respectively, n=12). The reduction in lag time and time to peak
was more pronounced than that obtained after eliciting platelet activation
with Ristocetin. Preincubation of Plts with E. coli also increased the velocity
index of TG compared to PRP alone (p=0,005; n=12).
Static adhesion of Pts to endothelium was studied by stimulating fresh
washed Plts with E. coli for 30min and then co-incubating them with HUVEC.
After 20 min, an increased number of bacterial-activated Plts were adhered to
HUVEC, compared with unstimulated Pts. Moreover, visible Plts aggregates
were observed, which were positive for fibrin immunostaining, suggesting
clot formation during the interaction of Plts with E. coli O111.
Our findings show that Plts activated by bacteria results in an enhanced
platelet procoagulant activity and adhesion to endothelium. By extension,
these in vitro results suggest that platelets play an important role in the
prothrombotic state associated with bacterial infections. | |
