Thrombin generation test based on a 96-channel pipettor for evaluation of FXIa procoagulant activity in pharmaceuticals

Leonid A. Parunov, Maria E. Shea, Yideng Liang, Stepan S. Surov, Maitreyi Chattopadhyay, Timothy K. Lee, Dorothy E. Scott, Mikhail V. Ovanesov

Published: 2021-07-01 DOI: 10.1038/s41596-021-00568-4

Thrombin generation assay

FXIa procoagulant activity

Immune globulin products

Quality control

Semiautomated analysis

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Thrombin generation (TG) assays are used widely to investigate both diseases and drugs that impact thrombosis and bleeding. TG assays were also instrumental in the identification of thrombogenic impurities in immune globulin products, which were associate
Introduction
Materials
Procedure
Troubleshooting
Timing
Anticipated results
References
ACKNOWLEDGMENTS
ACKNOWLEDGMENTS

Pitney, W. R. & Dacie, J. V. A simple method of studying the generation of thrombin in recalcified plasma. J. Clin. Pathol. 6, 9–14 (1953).
Macfarlane, R. G. & Biggs, R. A thrombin generation test. J. Clin. Pathol. 6, 3–8 (1953).
Mann, K. G., Brummel, K. & Butenas, S. What is all that thrombin for? J. Thromb. Haemost. 1, 1504–1514 (2003).
Hemker, H. C. & Al Dieri, R. Age-dependency of thrombin generation. Thromb. Haemost. 95, 756–757 (2006).
Sridhar, G. et al. Immune globulins and same-day thrombotic events as recorded in a large health care database during 2008 to 2012. Transfusion 54, 2553–2565 (2014).
Ekezue, B. F. et al. Clotting factor product administration and same-day occurrence of thrombotic events, as recorded in a large healthcare database during 2008-2013. J Thromb Haemost 13, 2168–2179 (2015).
Liang, Y. et al. Detecting factor XIa in immune globulin products: commutability of international reference materials for traditional and global hemostasis assays. Res. Pract. Thromb. Haemost. 5, 211–222 (2020).
Gray, E., Wilmot, H., Hogwood, J. & Rigsby, P. Evaluation of the proposed WHO 1st reference reagent for activated blood coagulation Factor XI (FXIa), human (World Health Organization, 2012); http://apps.who.int/iris/handle/10665/78047
Gray, E. et al. Value assignment of the candidate 1st international standard for activated blood coagulation factor XI (FXIa), human, NIBSC code 13/100 (World Health Organization, 2014); http://apps.who.int/iris/handle/10665/137475
Jha, N. K. et al. Optimization of the thrombin generation test components to measure potency of factor VIII concentrates. Haemophilia 22, 780–789 (2016).
de Laat-Kremers, R. M. W., Ninivaggi, M., Devreese, K. M. J. & de Laat, B. Towards standardization of thrombin generation assays: inventory of thrombin generation methods based on results of an International Society of Thrombosis and Haemostasis Scientific Standardization Committee survey. J. Thromb. Haemost. http://doi.org/10.1111/jth.14863 (2020).
Kintigh, J., Monagle, P. & Ignjatovic, V. A review of commercially available thrombin generation assays. Res. Pract. Thromb. Haemost. 2, 42–48 (2018).
Dargaud, Y. et al. Standardisation of thrombin generation test—which reference plasma for TGT?: an international multicentre study. Thromb. Res. 125, 353–356 (2010).
Dargaud, Y. et al. Effect of standardization and normalization on imprecision of calibrated automated thrombography: an international multicentre study. Br. J. Haematol. 139, 303–309 (2007).
Duarte, R. C. F. et al. Standardization and evaluation of the performance of the thrombin generation test under hypo- and hypercoagulability conditions. Hematol. Transfus. Cell Ther. 41, 244–252 (2019).
Loeffen, R. et al. Preanalytic variables of thrombin generation: towards a standard procedure and validation of the method. J. Thromb. Haemost. 10, 2544–2554 (2012).
Roemisch, J. R. et al. Identification of activated FXI as the major biochemical root cause in IVIG batches associated with thromboembolic events. Analytical And experimental approaches resulting in corrective and preventive measures implemented into the Octagam® manufacturing process. WebmedCentral http://doi.org/10.9754/journal.wmc.2011.002002 (2011).
Butenas, S. et al. Factor XIa and tissue factor activity in patients with coronary artery disease. Thromb. Haemost. 99, 142–149 (2008).
Council of Europe. European Pharmacopoeia, Ch. 2.6.22. Activated Coagulation Factors, 177 (EDQM, 2004).
Gray, E., Wilmot, H., Roberts, G., Atkinson, E. & Dougall, T. An international collaborative study to establish the 2nd international standard for activated factor IX (FIXa) (World Health Organization, 2017); http://apps.who.int/iris/handle/10665/260262
Parunov, L. A. et al. Thrombin generation assay modifications needed for its application to monitoring of replacement therapy for haemophilia. Haemophilia 27, e129–e132 (2021).
Tegegn, T. Z. et al. Characterization of procoagulant extracellular vesicles and platelet membrane disintegration in DMSO-cryopreserved platelets. J. Extracell. Vesicles 5, 30422 (2016).
Liang, Y., Woodle, S. A., Shibeko, A. M., Lee, T. K. & Ovanesov, M. V. Correction of microplate effects improves performance of the thrombin generation test. Thromb. J. 11, 12–12 (2013).
Woodle, S. A., Shibeko, A. M., Lee, T. K. & Ovanesov, M. V. Determining the impact of instrument variation and automated software algorithms on the TGT in hemophilia and normalized plasma. Thromb. Res. 132, 374–380 (2013).
Chang, W. C., Jackson, J. W., Machlus, K. R., Wolberg, A. S. & Ovanesov, M. V. Comparative analysis of thrombin calibration algorithms and correction for thrombin-α2macroglobulin activity. J. Clin. Med. 9, 3077 (2020).
Shestopal, S. A. et al. Expression and characterization of a codon-optimized blood coagulation factor VIII. J. Thromb. Haemost. 15, 709–720 (2017).

Thrombin generation test based on a 96-channel pipettor for evaluation of FXIa procoagulant activity in pharmaceuticals

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