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

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.

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

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]