PMID- 25096922
OWN - NLM
STAT- MEDLINE
DCOM- 20150622
LR  - 20140909
IS  - 1095-8320 (Electronic)
IS  - 1045-1056 (Linking)
VI  - 42
IP  - 5
DP  - 2014 Sep
TI  - Quantifying the thrombogenic potential of human plasma-derived immunoglobulin 
      products.
PG  - 260-70
LID - S1045-1056(14)00068-2 [pii]
LID - 10.1016/j.biologicals.2014.04.002 [doi]
AB  - 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.
CI  - Copyright (c) 2014 The International Alliance for Biological Standardization. 
      Published by Elsevier Ltd. All rights reserved.
FAU - Germishuizen, W A
AU  - Germishuizen WA
AD  - National Bioproducts Institute, Pinetown, South Africa.
FAU - Gyure, D C
AU  - Gyure DC
AD  - National Bioproducts Institute, Pinetown, South Africa.
FAU - Stubbings, D
AU  - Stubbings D
AD  - National Bioproducts Institute, Pinetown, South Africa.
FAU - Burnouf, T
AU  - Burnouf T
AD  - Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical 
      University, 250 Wuxing St., Taipei City 110, Taiwan. Electronic address: 
      tburnou@attglobal.net.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140802
PL  - England
TA  - Biologicals
JT  - Biologicals : journal of the International Association of Biological 
      Standardization
JID - 9004494
RN  - 0 (Biological Products)
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Immunologic Factors)
RN  - EC 3.4.21.27 (Factor XIa)
SB  - IM
MH  - Animals
MH  - Biological Products/*adverse effects/*blood/standards
MH  - Blood Coagulation Factors/adverse effects/isolation & purification
MH  - Chemistry, Pharmaceutical
MH  - Drug Contamination/prevention & control
MH  - Factor XIa/adverse effects/isolation & purification
MH  - Humans
MH  - Immunoglobulin G/*adverse effects/*blood
MH  - Immunoglobulins, Intravenous/adverse effects/standards
MH  - Immunologic Factors/adverse effects/blood
MH  - Risk Assessment
MH  - Thromboembolism/blood/*etiology/immunology
OTO - NOTNLM
OT  - FXIa
OT  - IVIG
OT  - Procoagulant
OT  - SCIG
OT  - Thrombosis
EDAT- 2014/08/07 06:00
MHDA- 2015/06/24 06:00
CRDT- 2014/08/07 06:00
PHST- 2014/01/30 00:00 [received]
PHST- 2014/04/24 00:00 [revised]
PHST- 2014/04/29 00:00 [accepted]
PHST- 2014/08/07 06:00 [entrez]
PHST- 2014/08/07 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
AID - S1045-1056(14)00068-2 [pii]
AID - 10.1016/j.biologicals.2014.04.002 [doi]
PST - ppublish
SO  - Biologicals. 2014 Sep;42(5):260-70. doi: 10.1016/j.biologicals.2014.04.002. Epub 
      2014 Aug 2.