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© Borgis - Nowa Pediatria 3/2018, s. 70-75 | DOI: 10.25121/NP.2018.22.3.70
*Marcus Picard-Maureau, Marek Z. Paśka
Platelet transfusion associated risks and improvement of platelet transfusion safety with Amotosalen/UVA pathogen inactivation technology
Ryzyka związane z transfuzją płytek krwi i sposoby podniesienia bezpieczeństwa przy użyciu technologii inaktywacji patogenów z wykorzystaniem Amotosalenu i światła UVA
Cerus Europe B.V., Stationsstraat 79-D, 3811 MH Amersfoort, The Netherlands
Despite the introduction of multiple measures to minimize the risk of transfusion-transmitted infections, there is still a residual risk of platelet transfusions, especially but not only for bacterial sepsis. Recently, the importance of a reliable hemovigilance system has been underlined and an up to 10-fold difference in the reporting of bacterial transmissions between active and passive reporting has been demonstrated. Another reason for a misjudging of the blood safety may derive from the fact that some pathogens cause obvious damage to critically ill and/or immunocompromised patients only and asymptomatic infections in immuno-competent recipients and thus are not being reported. Pathogen inactivation for platelets, a proactive approach not only broadly inactivating pathogens, but also white blood cells, could minimize the risk of transfusion transmitted infections and graft versus host disease due to residual leukocytes. Only the INTERCEPT technology has received approvals from the regulatory agencies in France, Germany and Switzerland, United States and Canada. That technology utilizes photoactive methods to modify nucleic acids. Long-term routine clinical experience, also with children and neonates, shows the safety and efficacy of INTERCEPT platelet transfusions. The national hemovigilance data of Switzerland, France and Belgium as well as single-center routine use studies show an improved clinical outcome in the acute as well as in the prophylactic setting with a significant decrease in septic and other non-hemolytic transfusion reactions, as well as prevention of graft-versus-host disease.
Platelet transfusion safety
Despite multiple improvements in the last decades like enhanced disinfection of the donor’s venipuncture site, leukoreduction, and the introduction of new donor screening tests there is a residual risk of pathogen transmission by transfusion of platelets. There are 77 transfusion-transmissible infectious pathogens currently known, and the number is growing constantly (1). The highest platelet transfusion-associated risk is still the bacterial contamination, with an average rate of 1:1000-1:2000 platelet concentrates being contaminated as shown by bacterial culture testing with no significant difference between apheresis and whole-blood-derived platelet units (2-4). The source of platelet contamination is in the majority of cases trace amounts of bacteria from the donors’ skin, but cases of contamination from transient donor bacteremia due to translocation from gut, small wounds or other sources cannot be excluded. In platelet units, many bacteria species find ideal growth conditions during storage which is performed at room temperature. Bacterial culture screening post production fails to detect large numbers of bacterially infected units and does not provide protection against septic transfusion reactions (STR) (5, 6). A recent active surveillance study from an American tertiary care academic hospital showed an average rate of transfused contaminated platelet concentrates of 1:2572 (20 of 51.440) despite negative initial bacterial culture testing post production (6). In multiple cases the patients showed signs of STR (retrospective analysis of patient charts), which were not recognized/reported by the treating physicians. There is evidence pointing towards a significant underreporting of STR (6, 7). Hemovigilance data from France, Belgium and Switzerland for the years 2005-2016 showed that the rate of septic transfusion reactions may be completely abolished by the implementation of pathogen inactivation (Amotosalen/UVA) (7). This approach holds more promise than the continuous implementation of new tests for newly emerging pathogens or the attempts to improve for example the performance of the existing tests for bacteria.
Interestingly, new Human-Immunodeficiency-Virus (HIV) and Hepatitis-B-Virus (HBV) variants have been ranked as high perceived risk for blood safety (position 2 and 10 of 77 respectively) during an international panel of experts rating (8). Indeed there are multiple cases of HIV and HBV transmission by blood transfusion described, which occurred despite serological and nucleic acid testing (NAT), likely because of viral variants and/or low viral loads below the limit of detection (9-11). A Polish study questions the effectiveness of the current donor deferral policy to reduce the risk of blood donations from donors carrying viruses in the early phase of infection (window period) when viral detection by standard blood screening measures often fails (12). The authors revealed that donor questionnaires about their risk behavior prior to donation were often not answered correctly. Besides these “classical” threats to transfusion, Hepatitis E is now one of the pathogens in the focus of the discussions. The seroprevalence for Hepatitis-E-Virus (HEV) is relatively high in Poland, and a recent study identified one of 2109 donors as HEV-positive by NAT, extrapolating 267 potential cases of transfusion-transmitted HEV annually (13). However, the clinical significance of such transmissions is questionable. A British study showed that only one of 43 patients which were infected by HEV during transfusion developed mild symptoms of hepatitis (14), and a German study showed that 6 patients which were infected by HEV during transfusion did not develop any symptoms (15). HEV is usually transmitted fecal-orally; the virus in blood is morphologically different from the virus found in feces and less infectious (16). HEV transmission by blood donation may still be a risk for immunosuppressed patients requiring multiple transfusions, which could potentially develop chronic infection (17). Outbreaks and spread of emerging arboviruses like Dengue Virus (DENV), Chikungunya Virus (CHIKV), West Nile Virus (WNV), Zika Virus (ZIKV) or Yellow Fever Virus (YFV) are an increasing threat for blood safety. The vector mosquitos capable of transmitting such pathogens are spreading through Europe from south to North, already endemic at the Mediterranean coast (Spain, France, Italy, Croatia, Greece) and south-east Europe (Bulgaria, West-Turkey) and introduced in Austria, Germany and even the Netherlands (18). WNV is currently endemic (2017 season) in Austria, Turkey, Northern Italy, Hungary, Croatia, Bulgaria, Greece and Spain (18). Since approx. 80% of virus-carriers are asymptomatic and may donate blood (19), there is a high risk for blood safety. Chikungunya outbreaks have been reported in France and Italy; recently an outbreak in the Lazio region (Rome) was confirmed in September 2017 (18) and led to a halt in platelet production for many blood banks. In the years 2010-2014, 1510 confirmed DENV infection cases have been reported in the European Union (18). Since this infection proceeds asymptomatic in approx. 80% of carriers (20), they represent a high potential risk as donors, and also a significant underreporting in the recipients is expected.
Especially in the field of hemato-oncology, recipients of blood transfusions have an impaired health, and are often immunocompromised. Pathogens which would lead to no or mild symptoms in healthy individuals may impact that patient group severely. Taking a significant underreporting of such infections due to non-detection and non-recognition into account (6, 7), additional layers of safety would be beneficial. Pathogen inactivation technology is a proactive approach to inactivate bacteria, viruses and parasites in blood components, further reducing the risk of STR.
Amotosalen/UVA pathogen inactivation technology

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otrzymano: 2018-07-13
zaakceptowano do druku: 2018-08-03

Adres do korespondencji:
*Marcus Picard-Maureau
Cerus Europe B.V., Stationsstraat 79-D, 3811 MH Amersfoort, The Netherlands
Phone: +31 33-496-0600

Nowa Pediatria 3/2018
Strona internetowa czasopisma Nowa Pediatria