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A collaborative study to harmonize thrombin generation assays for measurement of procoagulant activity in immune globulins

1US Food & Drug Administration, Silver Spring, Maryland, United States, 2US Food and Drug Administration, Silver Spring, Maryland, United States, 3National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, Potters Bar, England, United Kingdom

Abstract Number: OC 17.3

Meeting: ISTH 2022 Congress

Theme: Diagnostics and OMICs » Laboratory Diagnostics

Background: Thrombin generation (TG) assay is widely used to identify procoagulant samples of immune globulin (IG) product, yet there have been issues with reproducibility of results and lab-to-lab variability. In addition, there is a lack of a standardized TG assay protocol to measure procoagulant activity in IG products.

Aims: To address these issues, the Global Working Group for the Measurement of Procoagulant Activity of Immunoglobulins organized a study with 10 participants, including IG manufacturers, TG kit manufacturers and national regulatory bodies.

Methods: Performance of a total of 13 TG methods was evaluated. The methods included assays based on reagent kits from Technothrombin (Technoclone) and Calibrated Automated Thrombogram (Stago), as well as both automated and manual TG versions. Participants tested 7 IG samples of varying procoagulant activity and evaluated assay conditions (e.g., tissue factor and phospholipids, plasma, or diluent) that can deliver robust assay performance and a consistent response to a wide range of procoagulant samples. Potencies of samples were analyzed centrally using TG parameters reported by participants. The different TG parameters were also compared. All TG methods were evaluated by limit test using thrombin peak height value of a low activity IG sample as cut-off.

Results: Most labs were able to discern between samples with low and high activity. Quantitative measurement of procoagulant activity was found sensitive to assay conditions, which were different between labs. Regardless of the source of reagents used, good agreement was observed between labs that had optimized their assays (e.g., used lower tissue factor levels, FXI-deficient plasma) to be sensitive to a wide range of IG samples.

Conclusion(s): Further analysis of this study may help with standardization of TG assay techniques in quality control and clinical laboratory applications.

To cite this abstract in AMA style:

Shea M, Parunov L, Williams S, Hogwood J, Surov S, Liang Y, Gray E, Ovanesov M. A collaborative study to harmonize thrombin generation assays for measurement of procoagulant activity in immune globulins [abstract]. https://abstracts.isth.org/abstract/a-collaborative-study-to-harmonize-thrombin-generation-assays-for-measurement-of-procoagulant-activity-in-immune-globulins/. Accessed November 30, 2023.

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