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Contact activation: important to consider when measuring the contribution of tissue factor-bearing microparticles to thrombin generation using phospholipid-containing reagents
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-1920-3962
2014 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 12, no 4, p. 515-518Article in journal (Refereed) Published
Abstract [en]

Background: A commercial MP reagent containing phospholipids is used for thrombin generation (TG) measurements to estimate the procoagulant activity of microparticles (MPs). Previous reports have shown that contact activation affects TG when TF levels are low, and that addition of phospholipids might augment this effect.

Objectives: To quantify the impact of contact activation on TG in the presence of phospholipids and low/no TF, as is the case using a commercially available MP-reagent. Methods Thrombin generation was analyzed using MP- or platelet-rich plasma (PRP)-reagent in the presence and absence of corn trypsin inhibitor and anti-TF antibodies, respectively. To quantify the impact of different experimental parameters on contact activation, microparticle-depleted plasma was analyzed in the presence of different concentrations of phospholipids, TF and/or contact activating agents (kaolin).

Results: Even with low contact activating blood collection tubes, substantial thrombin generation was observed with the MP-reagent, but this was completely inhibited by addition of corn trypsin inhibitor. Control experiments illustrate that the phospholipids in the reagent play a major role in enhancing TG initiated by FXIIa. Even with the PRP-reagent, which is recommended for determining the content of phospholipids from MPs, TG was partly dependent on contact activation.

Conclusions: Contact activation plays a major role in TG when using reagents/samples containing phospholipids but little or no tissue factor. This needs to be considered and accounted for in future clinical studies using TG to assess the procoagulant activity of MPs.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014. Vol. 12, no 4, p. 515-518
Keywords [en]
Cell-derived microparticles, thromboplastin, blood coagulation, thrombin, factor XII
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:oru:diva-66032DOI: 10.1111/jth.12503ISI: 000334157000012PubMedID: 24405583Scopus ID: 2-s2.0-84898049593OAI: oai:DiVA.org:oru-66032DiVA, id: diva2:1192614
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2019-03-26Bibliographically approved

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