Pathogen reduction/inactivation of products for the treatment of bleeding disorders: what are the processes and what should we say to patients?

Giovanni Di Minno, David Navarro, Carlo Federico Perno, Mariana Canaro, Lutz Gürtler, James W Ironside, Hermann Eichler, Andreas Tiede, Giovanni Di Minno, David Navarro, Carlo Federico Perno, Mariana Canaro, Lutz Gürtler, James W Ironside, Hermann Eichler, Andreas Tiede

Abstract

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered.

Keywords: Bleeding disorder; Blood; Clotting; Inactivation; Infection risk; Pathogen; Patient information; Removal; Virus.

Conflict of interest statement

Conflict of interest

AT has received grants and personal fees from Bayer, grants and personal fees from Baxter, grants and personal fees from Biotest, grants and personal fees from CSL Behring, grants and personal fees from Novo Nordisk, grants and personal fees from Pfizer and grants and personal fees from Octapharma, during the conduct of the study.

CFP has received grants as bureau speaker, consultant, or advisor, from Gilead, Merck Sharp and Dohme, Roche, Pfizer, Abbott, Bristol-Myers Squibb, VIIV and Boehringer Ingelheim. None of these personal activities is in conflict with the opinions he expressed in this manuscript.

DN has received honoraria for conferences from Pfizer, Roche Pharma, Roche Diagnostics, Abbott, MSD and Astellas.

GDM has disclosed the following financial relationships: speaker or a member of a speaker bureau for Boehringer Ingelheim, Sanofi-Aventis, Bayer, Novo Nordisk, Pfizer, Biotest, and Grifols. Consultant or ad hoc speaker/consultant for Boehringer Ingelheim, Eli-Lilly, Sanofi-Aventis, Bayer, CSL Behring, Novo Nordisk, Pfizer, Biotest and Grifols.

HE has received grants, honoraria for conferences and consultancy from Bayer; grants and personal fees from Baxter; grants, honoraria for conferences and consultancy from Biotest; grants, honoraria for conferences and consultancy from CSL Behring and honoraria for conferences and consultancy from Novo Nordisk.

JWI has received personal fees from Piramal, grants from the Department of Health and the Medical Research Council, UK, outside the submitted work.

MC has received research grants, lecture fees and honoraria for consultancy from Baxter, Bayer and Pfizer.

LG reports no potential conflicts of interest.

Funding information

Medical writing assistance was provided by Hanna Mourad-Agha of inScience Communications, Springer Healthcare. This assistance was funded by Pfizer.

Figures

Fig. 1
Fig. 1
Stepwise reduction of pathogen transmission risk. Bacterial presence is routinely tested in platelet concentrates (PC) by anaerobic and aerobic cultures or by flow cytometry (discussed in the Preparation of blood-derived cellular products section). The applicability of purification and inactivation processes is limited, and is not yet possible for red blood cells (RBC). NAT nucleic acid testing. This figure was designed by the authors
Fig. 2
Fig. 2
Schematic depicting methods for the separation and storage of blood-derived cellular products and plasma. a Platelet-rich plasma is produced by separation of RBC followed by leukoreduction. b Buffy coat is obtained after separation of plasma and the platelet and leukocyte enriched cell fraction from RBC either from one individual or from pooling several donations followed by leukoreduction to get PC. c General overview of blood processing after donor selection and testing. RBC is always provided by individual donation, while a pool of 4–6 blood donations or plasmapheresis is used for preparation of PC. Between 1000 and >10,000 plasma donations are pooled for protein preparation as FVIII and FIX [24, 25]. Non-UK plasma is used in all countries to avoid the risk of prion contamination; in the UK, non-UK plasma is used for patients born after 1 January 1996 [24]. HBV hepatitis B virus, HCV hepatitis C virus, HIV human immunodeficiency virus, HTLV-1 human T-lymphotropic virus type 1. This figure was adapted from the Handbook for Transfusion Medicine, 5th Edition [24] and Vassallo and Murphy 2006 [25]

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