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

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

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

<div><p>Background</p><p>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 <i>ex vivo</i> study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied.</p><p>Methods</p><p>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.</p><p>Results</p><p>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% <i>vs</i>. 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. <i>Ex vivo</i> data were reproducible with the results of the mathematical simulation of TG.</p><p>Conclusion</p><p>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.</p></div

The Folk Song as a Source of Inspiration in Activities in Music Lessons in Primary Schools

Teachers often use folk songs as a means to teach children singing in tune and other musical skills or music theory. However, a deeper knowledge of the song itself happens to be missing. Yet, learning more about the music, looking deeper into its core can open new possibilities of its use in the classroom. The aim of this work is to demonstrate the path that a teacher should go through when, trying to gather knowledge about a folk song. Folk music is no more as popular as it used to be. It is therefore necessary for the teacher to spend more energy on the preparation to make it more attractive for the students. Folk song has the important feature of flexibility. The end of the 20lh century brought a new style of music combining folk songs with pop music. Its authors find inspiration in folklore, making it the basis of their own creative work. Such music thus reveals another possibility to bring the folk song closer to the today's audience and especially the young generation. Nevertheless, for the practical part I have chosen a different strategy: through encountering the folk music (songs of the southern Bohemia in this case) children learn about some features of modern pop music (from jazz through mid stream pop song to pop music. Powered by TCPDF (www.tcpdf.org

Coagulation factor and inhibitor levels.

<p>Coagulation factor and inhibitor levels.</p

Effects of anti-FIXa (RB006) and anti-TFPI (BAX499) alone or in combination on thrombin generation parameters.

<p>Effects of anti-FIXa (RB006) and anti-TFPI (BAX499) alone or in combination on thrombin generation parameters.</p

Maternal and cord coagulation factors and inhibitors.

<p>Adult levels set at 100% are shown for comparison. Maternal and cord values expressed as mean ± standard deviation (SD).</p

Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples - Fig 4

<p><b>Panels A-F.</b> Mathematical modeling of thrombin generation in adult, maternal and cord plasma. (A) native samples; (B) with anti-FIXa (RB006), 24 μg/ml; (C) with anti-TFPI (BAX499), 200 nM; (D-F) with varying levels (200%-0.1%) of FIX. 100% FIX activity equals 70 nM, 140 nM and 31 nM in adult, maternal and cord plasma, respectively.</p