Cell-derived vesicles exposing coagulant tissue factor in saliva

Berckmans, René J.; Sturk, Auguste; Tienen, Laurens M. van; Schaap, M. C. L.; Nieuwland, Rienk

doi:10.1182/blood-2010-06-290460

Cited by 173 publications

(172 citation statements)

References 33 publications

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“…Based on comparison of TG curves induced by saliva or r‐TF, we estimated the concentration of TF in saliva to be in the order of 1‐2 ng/mL, consistent with literature 5, 12…”

Section: Resultssupporting

confidence: 84%

“…Besides blood, another autologous body fluid, namely saliva, is in constant contact with the wound. Saliva was previously demonstrated to contain extracellular vesicle‐derived TF3, 4 capable of triggering coagulation, as apparent from a shortened clotting time of autologous plasma and whole blood 5. TF in saliva is bound to the membrane of exosomes released from epithelial cells 5.…”

Section: Introductionmentioning

confidence: 99%

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Salivary tissue factor induces thrombin generation in a diurnal rhythm

Vorm

Brouwers²,

Mondria

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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BackgroundUpon tooth extraction, extravascular tissue factor (TF) initiates coagulation to arrest bleeding. Additionally, saliva is in constant contact with the wound and contains extracellular vesicle‐derived procoagulant TF. Since the duration of postextraction bleeding is highly variable between patients, we hypothesized this may be caused by variation in saliva‐derived TF‐induced clotting activity.ObjectivesWe aimed to assess the variability of saliva‐induced thrombin generation (TG) in healthy individuals.Methods TG was performed according to the calibrated automated thrombinography (CAT) method. Diluted saliva was added (instead of recombinant TF and phospholipids [PL]) to normal pooled plasma (NPP) in the absence/presence of anti‐TF antibodies. Saliva was collected from healthy individuals in the morning, afternoon and evening.ResultsAddition of saliva to NPP induced TG curves similar to those induced by r‐TF and PL. Moreover, addition of anti‐TF antibodies abolished saliva‐induced TG, indicating TF‐dependence. A large inter‐individual variability (peak CV 31%, range 73‐220 nmol/L thrombin) in saliva‐induced TG was observed. Interestingly, within subjects, saliva‐induced TG was significantly (P = 0.009) increased in the morning (167 ± 40 nmol/L thrombin) compared to the afternoon (124 ± 39 nmol/L thrombin) and evening (123 ± 38 nmol/L thrombin). This diurnal variation was not attributable to gingival stimulation or damage induced by tooth brushing.ConclusionsWe identified a diurnal rhythm in salivary TF activity that may have implications for tooth extraction and dental surgery, as performing invasive procedures in the morning may be beneficial for rapid coagulation. Future studies should correlate salivary TF to clinical outcome (ie, postextraction bleeding) and assess a possible relation with bacterial status in the oral cavity.

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“…Based on comparison of TG curves induced by saliva or r‐TF, we estimated the concentration of TF in saliva to be in the order of 1‐2 ng/mL, consistent with literature 5, 12…”

Section: Resultssupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Salivary tissue factor induces thrombin generation in a diurnal rhythm

Vorm

Brouwers²,

Mondria

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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“…This is a transmembrane protein, tissue factor (TF), which activates coagulation factor VII to factor VIIa, and thereby triggers the clotting of blood. In physiological conditions, TF is abundantly present on EVs in normal human saliva (and other body fluids such as urine and lacrima), and the ability of EVs from saliva to trigger blood clotting is comparable to snake venom [16]. …”

Section: General Perspectives On Ev Biomarkersmentioning

confidence: 99%

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

Clayton

Buschmann

Byrd

et al. 2018

J of Extracellular Vesicle

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This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.

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“…Vesiculation was studied in cancer cells [9][10][11][12][13] and was shown in vivo to be connected to the impact of cancer-associated coagulopathies. [14][15][16][17] Furthermore, nanoparticles have also been found in isolates from other body fluids, such as synovial fluid of inflamed joints, 18 pleural fluid, 19 ascites, 19 saliva, 20,21 and urine.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles isolated from blood: a reflection of vesiculability of blood cells during the isolation process

Šuštar¹,

Bedina-Zavec²,

Stukelj³

et al. 2011

IJN

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Background: Shedding of nanoparticles from the cell membrane is a common process in all cells. These nanoparticles are present in body fluids and can be harvested by isolation. To collect circulating nanoparticles from blood, a standard procedure consisting of repeated centrifugation and washing is applied to the blood samples. Nanoparticles can also be shed from blood cells during the isolation process, so it is unclear whether nanoparticles found in the isolated material are present in blood at sampling or if are they created from the blood cells during the isolation process. We addressed this question by determination of the morphology and identity of nanoparticles harvested from blood. Methods: The isolates were visualized by scanning electron microscopy, analyzed by flow cytometry, and nanoparticle shapes were determined theoretically. Results: The average size of nanoparticles was about 300 nm, and numerous residual blood cells were found in the isolates. The shapes of nanoparticles corresponded to the theoretical shapes obtained by minimization of the membrane free energy, indicating that these nanoparticles can be identified as vesicles. The concentration and size of nanoparticles in blood isolates was sensitive to the temperature during isolation. We demonstrated that at lower temperatures, the nanoparticle concentration was higher, while the nanoparticles were on average smaller. Conclusion:These results indicate that a large pool of nanoparticles is produced after blood sampling. The shapes of deformed blood cells found in the isolates indicate how fragmentation of blood cells may take place. The results show that the contents of isolates reflect the properties of blood cells and their interaction with the surrounding solution (rather than representing only nanoparticles present in blood at sampling) which differ in different diseases and may therefore present a relevant clinical parameter.

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Cell-derived vesicles exposing coagulant tissue factor in saliva

Cited by 173 publications

References 33 publications

Salivary tissue factor induces thrombin generation in a diurnal rhythm

Salivary tissue factor induces thrombin generation in a diurnal rhythm

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

Nanoparticles isolated from blood: a reflection of vesiculability of blood cells during the isolation process

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