Page 192 - Haematologica May 2022

Letters to the Editor
APC response characterized by increased thrombin for- mation rates and simultaneously decreased APC forma- tion rates contributes to the increased thrombotic risk of patients with familial thrombosis. Further studies are now warranted to elucidate the pathophysiological and genetic basis of the described phenotype. Moreover, the data show that the SHAPE procedure is a useful tool to measure the functionality of the PC pathway, which is help- ful to investigate prothrombotic mechanisms in patients with thrombophilia without an established risk factor.
Sara Reda,* Nadine Schwarz,* Jens Müller, Johannes Oldenburg, Bernd Pötzsch# and Heiko Rühl#
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
*SR and NS contributed equally as co-first authors #BP and HR contributed equally as co-senior authors Correspondence:
HEIKO RÜHL - Heiko.Ruehl@ukbonn.de doi:10.3324/haematol.2021.280573
Received: December 21, 2021.
Accepted: January 31, 2022.
Pre-published: February 10, 2022.
Disclosures: BP and JM have a patent DE102007063902B3 including the aptamer HS02-52G binding to APC. An assay for the quantification of APC levels in human plasma, based on this aptamer, has been licensed to ImmBioMed, Pfungstadt, Germany. All other authors declare no conflicts of interest.
Contributions: HR, JM, and BP designed the experiments. SR, NS, and HR collected the data, SR and HR analyzed the data. SR, NS, JM, JO, BP, and HR drafted and edited the manuscript.
Funding: this work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 419450023. HR is recipient of a fellowship from the Stiftung Hämotherapie-Forschung (Hemotherapy Research Foundation).
Data-sharing statement: the datasets used and/or analyzed during the current study are available from the corresponding author on rea- sonable request. All authors have complete and on-going access to the study data.
References
1. Reitsma PH, Versteeg HH, Middeldorp S. Mechanistic view of risk
factors for venous thromboembolism. Arterioscler Thromb Vasc
Biol. 2012;32(3):563-568.
2. Klarin D, Busenkell E, Judy R, et al. Genome-wide association analy-
sis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease. Nat Genet. 2019;51(11):1574- 1579.
3. Lindström S, Wang L, Smith EN, et al. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. Blood. 2019;134(19):1645-1657.
4.Zöller B. Genetics of venous thromboembolism revised. Blood. 2019;134(19):1568-1570.
5. Segers O, van Oerle R, ten Cate H, Rosing J, Castoldi E. Thrombin generation as an intermediate phenotype for venous thrombosis. Thromb Haemost. 2010;103(1):114-122.
6. Rühl H, Winterhagen FI, Berens C, Müller J, Oldenburg J, Pötzsch B. In vivo thrombin generation and subsequent APC formation are increased in factor V Leiden carriers. Blood. 2018;131(13):1489-1492.
7. Rühl H, Berens C, Winterhagen FI, et al. Increased activated protein C response rates reduce the thrombotic risk of factor V Leiden car- riers but not of prothrombin 20210G>A Carriers. Circ Res. 2019;125(5):523-534.
8. Müller J, Friedrich M, Becher T, et al. Monitoring of plasma levels of activated protein C using a clinically applicable oligonucleotide- based enzyme capture assay. J Thromb Haemost. 2012;10(3):390- 398.
9. Keularts IM, Zivelin A, Seligsohn U, Hemker HC, Béguin S. The role of factor XI in thrombin generation induced by low concentrations of tissue factor. Thromb Haemost. 2001;85(6):1060-1065.
10. Rühl H, Berens C, Winterhagen A, Müller J, Oldenburg J, Pötzsch B. Label-free kinetic studies of hemostasis-related biomarkers includ- ing D-dimer using autologous serum transfusion. PLoS One. 2015;10(12):e0145012.
11. Bauer KA, Broekmans AW, Bertina RM, et al. Hemostatic enzyme generation in the blood of patients with hereditary protein C defi- ciency. Blood. 1988;71(5):1418-1426.
12. Medina P, Navarro S, Estellés A, et al. Contribution of polymor- phisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk. Thromb Haemost. 2004;91(5):905-911.
13. Navarro S, Medina P, Bonet E, et al. Association of the thrombo- modulin gene c.1418C>T polymorphism with thrombomodulin levels and with venous thrombosis risk. Arterioscler Thromb Vasc Biol. 2013;33(6):1435-1440.
14. Fridberg MJ, Hedner U, Roberts HR, Erhardtsen E. A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects. Blood Coagul Fibrinolysis. 2005;16(4):259-266.
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