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Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products.
Biologicals. 2014 Sep; 42(5):260-70.B

Abstract

Polyvalent immunoglobulin G (IgG) products obtained by fractionation of human plasma are used to treat a broad range of conditions, including immunodeficiency syndromes and autoimmune, inflammatory, and infectious diseases. Recent incidences of increased thromboembolic events (TEEs) associated with intravenous (IV) IgG (IVIG) led to recalls of some products and increased regulatory oversight of manufacturing processes in order to ensure that products are essentially free of procoagulant/thrombogenic plasma protein contaminants. Laboratory investigations have now identified activated factor XI (FXIa) as the likely causative agent of IVIG-related TEEs. Quantification of the thrombogenic potential is becoming a requirement made to fractionators (a) to validate the capacity of IVIG and subcutaneous IgG manufacturing processes to remove procoagulant contaminants and (b) to establish the safety of the final products. However, in the absence of a recommended test by the main regulatory authorities, several analytical approaches have been evaluated by fractionators, regulators, and university groups. This review focuses on the scientific rationale, merits, and applications of several analytical methods of quantifying the thrombogenic potential of IgG products and intermediates to meet the latest regulatory requirements.

Authors+Show Affiliations

National Bioproducts Institute, Pinetown, South Africa.National Bioproducts Institute, Pinetown, South Africa.National Bioproducts Institute, Pinetown, South Africa.Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, 250 Wuxing St., Taipei City 110, Taiwan. Electronic address: tburnou@attglobal.net.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25096922

Citation

Germishuizen, W A., et al. "Quantifying the Thrombogenic Potential of Human Plasma-derived Immunoglobulin Products." Biologicals : Journal of the International Association of Biological Standardization, vol. 42, no. 5, 2014, pp. 260-70.
Germishuizen WA, Gyure DC, Stubbings D, et al. Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products. Biologicals. 2014;42(5):260-70.
Germishuizen, W. A., Gyure, D. C., Stubbings, D., & Burnouf, T. (2014). Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products. Biologicals : Journal of the International Association of Biological Standardization, 42(5), 260-70. https://doi.org/10.1016/j.biologicals.2014.04.002
Germishuizen WA, et al. Quantifying the Thrombogenic Potential of Human Plasma-derived Immunoglobulin Products. Biologicals. 2014;42(5):260-70. PubMed PMID: 25096922.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products. AU - Germishuizen,W A, AU - Gyure,D C, AU - Stubbings,D, AU - Burnouf,T, Y1 - 2014/08/02/ PY - 2014/01/30/received PY - 2014/04/24/revised PY - 2014/04/29/accepted PY - 2014/8/7/entrez PY - 2014/8/7/pubmed PY - 2015/6/24/medline KW - FXIa KW - IVIG KW - Procoagulant KW - SCIG KW - Thrombosis SP - 260 EP - 70 JF - Biologicals : journal of the International Association of Biological Standardization JO - Biologicals VL - 42 IS - 5 N2 - Polyvalent immunoglobulin G (IgG) products obtained by fractionation of human plasma are used to treat a broad range of conditions, including immunodeficiency syndromes and autoimmune, inflammatory, and infectious diseases. Recent incidences of increased thromboembolic events (TEEs) associated with intravenous (IV) IgG (IVIG) led to recalls of some products and increased regulatory oversight of manufacturing processes in order to ensure that products are essentially free of procoagulant/thrombogenic plasma protein contaminants. Laboratory investigations have now identified activated factor XI (FXIa) as the likely causative agent of IVIG-related TEEs. Quantification of the thrombogenic potential is becoming a requirement made to fractionators (a) to validate the capacity of IVIG and subcutaneous IgG manufacturing processes to remove procoagulant contaminants and (b) to establish the safety of the final products. However, in the absence of a recommended test by the main regulatory authorities, several analytical approaches have been evaluated by fractionators, regulators, and university groups. This review focuses on the scientific rationale, merits, and applications of several analytical methods of quantifying the thrombogenic potential of IgG products and intermediates to meet the latest regulatory requirements. SN - 1095-8320 UR - https://www.unboundmedicine.com/medline/citation/25096922/Quantifying_the_thrombogenic_potential_of_human_plasma_derived_immunoglobulin_products_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1045-1056(14)00068-2 DB - PRIME DP - Unbound Medicine ER -