title: Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Obstetric and Gynecology, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Nicklaus T
authors.initials: NT
authors.lastname: Rice
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Fania
authors.initials: F
authors.lastname: Szlam
authors.affiliation: School of Chemical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Varner
authors.affiliation: Department of Clinical Obstetric & Gynecology and Women's Health, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, United States of America.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Bernstein
authors.affiliation: Department of Mathematics, CCNY, New York, United States of America.
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Szlam
authors.affiliation: Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Kenichi A
authors.initials: KA
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D052157:Aptamers, Nucleotide / Q000737:chemistry; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002138:Calibration; D016022:Case-Control Studies; D003029:Coagulants / Q000737:chemistry; D003198:Computer Simulation; D015949:Factor IXa / Q000037:antagonists & inhibitors; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006487:Hemostasis; D006801:Humans; D015233:Models, Statistical; D008962:Models, Theoretical; D010949:Plasma / Q000378:metabolism; D011247:Pregnancy; D013917:Thrombin / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: C577143:ARC19499; D052157:Aptamers, Nucleotide; D003029:Coagulants; C515724:RB 006; D015949:Factor IXa; D013917:Thrombin