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Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays.
Res Pract Thromb Haemost. 2021 Jan; 5(1):211-222.RP

Abstract

Background

Activated coagulation factor XIa (FXIa) is an impurity and primary source of procoagulant activity in thrombosis-implicated immune globulin (IG) products. Several assays, of varying quality and precision are used to assess FXIa-like procoagulant activity in units relevant to their respective principles.

Objectives

To advance unified reporting, we sought to employ the World Health Organization reference reagents (RRs) to present the results of differing methodologies in units of FXIa activity and rank the sensitivity and robustness of these methodologies.

Methods

RR 11/236 served as a calibrator in several FXIa-sensitive blood coagulation tests: two commercial chromogenic FXIa assays (CAs); a nonactivated partial thromboplastin time (NaPTT); an in-house fibrin generation (FG) assay; an in-house thrombin generation (TG) assay; and an assay for FXIa- and kallikrein-like proteolytic activities based on cleavage of substrate SN13a. Some assays were tested in either normal or FXI-deficient plasma.

Results

Each method demonstrated a sigmoidal dose-response to RRs. NaPTT was the least sensitive to FXIa and the least precise; our in-house TG was the most sensitive; and the two CAs were the most precise. All methods, except for SN13a, which is less specific for thrombotic impurities, gave comparable (within 20% difference) FXIa activity assignments for IG lots.

Conclusions

Purified FXIa reference standards support quantitation of FXIa levels in IG products in all tested assay methodologies. This should help to standardize the measurement of thrombotic potentials in IG products and prevent products exhibiting high procoagulant activity from distribution for patient use. Further research is needed to address the effect of IG product-specific matrixes on assay performance.

Authors+Show Affiliations

Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33537546

Citation

Liang, Yideng, et al. "Detecting Factor XIa in Immune Globulin Products: Commutability of International Reference Materials for Traditional and Global Hemostasis Assays." Research and Practice in Thrombosis and Haemostasis, vol. 5, no. 1, 2021, pp. 211-222.
Liang Y, Jackson JW, Woodle SA, et al. Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays. Res Pract Thromb Haemost. 2021;5(1):211-222.
Liang, Y., Jackson, J. W., Woodle, S. A., Surov, S. S., Parunov, L. A., Scott, D. E., Weinstein, M., Lee, T. K., & Ovanesov, M. V. (2021). Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays. Research and Practice in Thrombosis and Haemostasis, 5(1), 211-222. https://doi.org/10.1002/rth2.12467
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. 2021;5(1):211-222. PubMed PMID: 33537546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays. AU - Liang,Yideng, AU - Jackson,Joseph W, AU - Woodle,Samuel A, AU - Surov,Stepan S, AU - Parunov,Leonid A, AU - Scott,Dorothy E, AU - Weinstein,Mark, AU - Lee,Timothy K, AU - Ovanesov,Mikhail V, Y1 - 2020/12/23/ PY - 2020/08/07/received PY - 2020/10/21/revised PY - 2020/11/03/accepted PY - 2021/2/4/entrez PY - 2021/2/5/pubmed PY - 2021/2/5/medline KW - blood coagulation tests KW - calibration KW - coagulation factor XIa KW - immune globulin KW - thrombin SP - 211 EP - 222 JF - Research and practice in thrombosis and haemostasis JO - Res Pract Thromb Haemost VL - 5 IS - 1 N2 - Background: Activated coagulation factor XIa (FXIa) is an impurity and primary source of procoagulant activity in thrombosis-implicated immune globulin (IG) products. Several assays, of varying quality and precision are used to assess FXIa-like procoagulant activity in units relevant to their respective principles. Objectives: To advance unified reporting, we sought to employ the World Health Organization reference reagents (RRs) to present the results of differing methodologies in units of FXIa activity and rank the sensitivity and robustness of these methodologies. Methods: RR 11/236 served as a calibrator in several FXIa-sensitive blood coagulation tests: two commercial chromogenic FXIa assays (CAs); a nonactivated partial thromboplastin time (NaPTT); an in-house fibrin generation (FG) assay; an in-house thrombin generation (TG) assay; and an assay for FXIa- and kallikrein-like proteolytic activities based on cleavage of substrate SN13a. Some assays were tested in either normal or FXI-deficient plasma. Results: Each method demonstrated a sigmoidal dose-response to RRs. NaPTT was the least sensitive to FXIa and the least precise; our in-house TG was the most sensitive; and the two CAs were the most precise. All methods, except for SN13a, which is less specific for thrombotic impurities, gave comparable (within 20% difference) FXIa activity assignments for IG lots. Conclusions: Purified FXIa reference standards support quantitation of FXIa levels in IG products in all tested assay methodologies. This should help to standardize the measurement of thrombotic potentials in IG products and prevent products exhibiting high procoagulant activity from distribution for patient use. Further research is needed to address the effect of IG product-specific matrixes on assay performance. SN - 2475-0379 UR - https://www.unboundmedicine.com/medline/citation/33537546/Detecting_factor_XIa_in_immune_globulin_products:_Commutability_of_international_reference_materials_for_traditional_and_global_hemostasis_assays_ L2 - https://doi.org/10.1002/rth2.12467 DB - PRIME DP - Unbound Medicine ER -
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