Flyvbjerg, Henrik

Markovich, Dmitriy

Røder, Gustav

Online Research Database In Technology

                       General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.  • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal   If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.     Downloaded from orbit.dtu.dk on: Dec 18, 2017An Analytical Approach to the ThrombogramMarkovich, Dmitriy; Røder, Gustav; Flyvbjerg, HenrikPublication date:2016Document VersionPeer reviewed versionLink back to DTU OrbitCitation (APA):Markovich, D., Røder, G., & Flyvbjerg, H. (2016). An Analytical Approach to the Thrombogram. Abstract from 3rdMaastricht Thrombin Summer School, Maastricht, Netherlands.An analytical approach to the thrombogramD. L. Markovich1, G. Røder2, and H. Flyvbjerg11 Stochastic Systems and Signals, Department of Micro- and Nanotechnology, TechnicalUniversity of Denmark, Denmark2 Global Research, Novo Nordisk A/S, DenmarkData from thrombin generation experiments are conventionally analyzed using the so-called thrombogram. Commercially available instruments do this automatically but are blackboxes: the exact method of analysis is hidden from the user.In research, flexible and transparent methods of data analysis are needed. Researchshould  not  be  limited  by  the  requirements  of  a  specific  experimental  setup or  a  specificprotocol. Here we present transparent and flexible analytical  methods of data analysis forthrombin generation experiments.We show that calibration signals can be described with Michaelis-Menten kinetics ofthe basic enzymatic reaction and that kinetic constants and the standard calibration factorused  by  CAT can  be  extracted  from  the  fits  to  raw  data.  We  also  show  that  thrombingeneration signals can be described with a phenomenological model based on the cascade ofbasic enzymatic reactions that includes damping by anti-enzymes. This model also accountsfor the contribution of α2 -macroglobulin-thrombin complex in the raw signal and separatesit from the contribution of thrombin.We compared our method with the commercially available CAT method, using the CATcalibration factor in both methods, and found the results to be similar. However, the differentinterpretation  of  the  calibration  factor  suggested  by  our  model  resulted  in  up  to  1.8 folddifference between  the values obtained with the two methods for ETP, peak, and velocityindex parameters.In conclusion, we have developed an analytical open-source method of data analysis inthrombin  generation  experiments.  It  is  flexible,  it  works  with  an  arbitrary  experimentalprotocol, and it operates on the raw data. Therefore, its performance can easily be assessedvisually, and its results are noise-robust and reliable.Source  of  funding:  Department  of  Micro-  and  Nanotechnology,  Technical  University  ofDenmarkConflict of interest: None

An Analytical Approach to the Thrombogram

http://orbit.dtu.dk/ws/files/127371964/abstract.pdf

An Analytical Approach to the Thrombogram

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