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In [1], the abstract was published incorrectly, therefore, it is now reproduced in full below:

P-WE-181

EspP, an extracellular serine protease from enterohemorrhagic Escherichia coli, induces coagulopathy in human plasma and fibrinolysis in whole blood

  1. Top of page
  2. EspP, an extracellular serine protease from enterohemorrhagic Escherichia coli, induces coagulopathy in human plasma and fibrinolysis in whole blood
  3. References

S. KHAN*, K. H. M. KUO†, E. BRNJAC‡, M. L. RAND§, E. F. PAI¶ and A. E. CHESNEY**

* Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; †Department of Medical Oncology and Hematology, University Health Network; ‡Department of Clinical Pathology, Sunnybrook Health Sciences Centre; §Division of Hematology, The Hospital for Sick Children; ¶Departments of Biochemistry, Molecular Genetics and Medical Biophysics, University of Toronto, and Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, University Health Network; and **Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Summary.  EspP (E. coli secreted serine protease) is a virulence factor in diarrhea-associated Hemolytic Uremic Syndrome. It cleaves human factor V in vitro (Brunder et al., Mol Microbiol 1997, 24: 767–78) and we have observed that EspP also cleaves factor VIII. Here, we further investigate the effects of EspP on hemostasis. Incubation of citrated whole blood (= 5 donors) with 1 mg mL−1 EspP at 37°C for 4 h prolonged the PT by 32.7 s (95% CI 26.7–38.8, = 0.0001), aPTT by 77.5 s (95% CI 56.4–98.6, = 0.0005) and TT by 10.2 s (95% CI 9.2–11.1, < 0.0001). Factor V activity decreased by 0.66 U mL−1 (95% CI 0.54–0.78, = 0.0001), factor VII by 0.74 U mL−1 (95% CI 0.40–1.07, = 0.004), factor VIII by 0.58 U mL−1 (95% CI 0.37–0.80, = 0.002) and factor XII by 0.46 U mL−1 (95% CI 0.27–0.65, = 0.005). Prothrombin activity decreased by 0.17 U mL−1 (95% CI 0.09–0.25, = 0.007) but remained above 0.70 U mL−1. Factors IX, X and XI activities were unchanged. Interestingly, when analyzed by whole blood thrombelastography (= 4 donors), reaction time (R) decreased by 7.0 min (95% CI 3.7–10.3, = 0.007), clot formation time (K) decreased by 0.86 min (95% CI 0.22–1.50, = 0.023), and clot kinetics (alpha angle) increased by 9.5 (95% CI 8.3–10.8, = 0.0002), suggesting an accelerated rate of platelet-fibrin clot formation. Moreover, maximum amplitude of clot (MA) and percent clot lysis (LY30) were indicative of enhanced fibrinolysis; MA decreased, and LY30 increased, by 25.9 mm (95% CI 11.0–40.8, = 0.012), and 27.1% (95% CI 17.5–71.7, = 0.15), respectively, when samples were incubated with EspP for 4 h, but by 21.9 mm (95% CI 10.8–31.3, = 0.009), and 40.5% (95% CI 18.6–62.3, = 0.010), respectively, when samples were incubated with EspP for only 2 h. Our results show that EspP alters hemostasis in vitro by decreasing the activities of factors V, VII, VIII and XII, by enhancing platelet-fibrin clot formation, and by accelerating fibrinolysis. Further work is required to delineate the mechanisms involved.

References

  1. Top of page
  2. EspP, an extracellular serine protease from enterohemorrhagic Escherichia coli, induces coagulopathy in human plasma and fibrinolysis in whole blood
  3. References
  • 1
    Khan S, Kuo KHM, Brnjac E, Rand ML, Pai EF, Chesney AE. EspP, an extracellular serine protease from enterohemorrhagic E. coli, induces coagulopathy in human plasma and fibrinolysis in whole blood. J Thromb Haemost 2011; 9 (Suppl. 2): P-WE-181.