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Author Notes:

E-mail: ktanaka@anes.umm.edu

Conceived and designed the experiments: NTR FS JDV PSB ADS KAT.

Performed the experiments: NTR FS KAT.

Analyzed the data: NTR FS JDV PSB ADS KAT.

Contributed reagents/materials/analysis tools: NTR FS JDV PSB ADS KAT.

Wrote the paper: NTR FS JDV PSB ADS KAT.

The authors have declared that no competing interests exist.

Subjects:

Keywords:

  • Multidisciplinary Sciences
  • FACTOR-IXA
  • CARDIOPULMONARY BYPASS
  • LOW ANTITHROMBIN
  • INHIBITOR TFPI
  • APTAMER BAX499
  • FACTOR VIIA
  • TISSUE
  • BLOOD
  • MECHANISM
  • Blood plasma
  • Thrombin
  • Coagulation factors
  • Pregnancy
  • Adults
  • Serine proteases
  • Platelets
  • Mathematical models

Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 11, Number 5

Publisher:

, Pages e0154127-e0154127

Type of Work:

Article | Final Publisher PDF

Abstract:

BACKGROUND: Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied. METHODS: Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG. RESULTS: Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG. CONCLUSION: Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT.

Copyright information:

© 2016 Rice et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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