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. 2017 Apr 12;7:843. doi: 10.1038/s41598-017-00927-w

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Thrombin inhibitors decrease dilution-induced hypercoagulation. The value of the corresponding parameter in undiluted plasma was taken as 100%. DF is a dilution factor. (a) - The increase of ETP during plasma dilution with NS decreases in the presence of AT. The final concentration of AT for each curve was constant and equal to (1) – 0; (2) – 0.145; (3) – 0.29; (4) – 0.58; and (5) – 0.87 IU/ml (n = 5–9). The ETP in diluted plasma differed from that in starting plasma in each series of experiments significantly beginning from DF = 1.5 for all the concentrations of AT, excepting 0.87 IU/ml (ANOVA, P < 0.05). The difference between the curves with and without AT was significant for DF = 2.5, 3 (curve 2); DF = 2, 2.5, 3 (curves 3 and 4); and DF = 1.5, 2, 2.5, 3 (curve 5). (b) – Changes of ETP in plasma diluted with NS supplemented with different concentrations of the direct thrombin inhibitor HC-025s-IOC. The concentration of the inhibitor in PE was equal to: (1) – 0; (2) – 0.25; (3) – 0.5; and (4) – 1 µМ (n = 3). Coagulation was activated using TF (4 pM). The difference between the initial plasma and the same diluted plasma was significant for all DFs at any concentration of inhibitor (ANOVA, P < 0.05). The difference between the curves in the presence and absence of inhibitor was significant for all the curves, excluding curves 2 and 3 at DF = 1.5. (c) - Initial clot growth rate (Vi) under plasma dilution with NS in the presence of different concentrations of thrombin inhibitors, and under the different methods of coagulation activation (n = 3 pools, each of 3 plasma samples). (1) - Contact activation (glass, n = 3); (2) - contact activation and AT in all the samples at the concentration of 0.87 IU/ml (n = 3); (3) – activation by TF (4 pM, n = 3); (4) – activation by TF and dilution with NS containing 8 µМ of the thrombin inhibitor HC-025s-IOC (n = 3). The mean values ± SD are shown. All the obtained differences were significant (α = 0.05 and statistical power of 80%) excluding the difference between curves 1 and 2 at DF = 1.5.