A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment

Background and Objectives: A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT™ Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. Materials and Methods: This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0–4), and causal relationship to PCT-PLT transfusion. Results: Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0·6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0·4%) and urticaria (41, 0·2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0·1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. Conclusion: This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components.publishedVersio

The poetry of Celtic places

This paper examines the radical shift in the place of Celts in the French imagination during the course of the nineteenth century, by focusing on two versions of a passage describing Wales by Michelet: the first written in his travel journal (1834), the second published by his widow (1893). Wales, by virtue of being a Celtic place, allows Michelet to deepen his understanding of France. Whereas juxtaposition of the two versions of his text reveals something of the French state’s attitude toward the ambiguously domestic and exotic Celtic “other.

A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment

Background and Objectives: A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT™ Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. Materials and Methods: This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0–4), and causal relationship to PCT-PLT transfusion. Results: Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0·6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0·4%) and urticaria (41, 0·2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0·1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. Conclusion: This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components

Impact of leucocyte depletion and prion reduction filters on TSE blood borne transmission

The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters

Comparison of the Hemostatic Efficacy of Pathogen-Reduced Platelets vs Untreated Platelets in Patients With Thrombocytopenia and Malignant Hematologic Diseases

International audienc

TSE occurrence in VRQ/VRQ TSE free sheep transfused with blood labile products prepared from Scrapie infected sheep.

<p>Each whole blood pool was constituted by mixing 700 mL from 3 VRQ/VRQ sheep orally inoculated with PG127 classical scrapie isolate. Aliquots of whole blood were processed according to the design described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042019#pone-0042019-g001" target="_blank">Figure 1</a>. Obtained products were then transfused in VRQ/VRQ TSE free recipient sheep. Recipients were monitored for clinical TSE occurrence. Clinically affected animals were culled when displaying locomotor difficulties that could impair their abilities to feed. The remaining apparently healthy recipients were killed 400 days after transfusion. Systematic detection of abnormal PrP (using both immunohistochemistry and western-blot) in lymphoid tissues (LRS) and central nervous system (CNS) was carried out in recipients as to establish their status.</p

TSE occurrence in VRQ/VRQ TSE free sheep transfused with frozen plasma and plasma fractions prepared from Scrapie infected sheep.

<p>Whole blood pool was constituted by mixing 600–700 mL from 3 VRQ/VRQ sheep orally inoculated with PG127 classical scrapie isolate. Aliquots of blood were processed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042019#pone-0042019-g001" target="_blank">Figure 1</a>. For each pool, plasma obtained from Inoculum 7 and 8 preparation lines were stored at −30°C. Decreasing amount of plasma (200 mL, 20 mL and 2 mL) were then transfused to VRQ/VRQ recipients. In parallel, 200 mL of plasma were submitted to standard cryoprecipitation procedure. Both supernatant and cryoprecipitate were intravenously administered to VRQ/VRQ recipient sheep. Recipients were monitored for clinical TSE occurrence. Clinically affected animals were culled when displaying locomotor difficulties that could impair their abilities to feed. The remaining apparently healthy recipients were killed 450 days after transfusion. Systematic detection of abnormal PrP (using both immunohistochemistry and western-blot) in lymphoid tissues (LRS) and central nervous system (CNS) was carried out in recipients as to establish their status.</p

Design of blood products preparation and filtration process.

<p>600 mL to 700 mL of whole blood were collected at the late stage of preclinical incubation from 15 VRQ/VRQ sheep orally inoculated with PG127 scrapie isolate. Blood from 3 sheep were pooled in a single pouch in order to obtain a volume higher than 1800 mL. Each pool was split into 5 parts that were individually processed according to the standard procedure applied in transfusion medicine. Obtained fractions were transfused or intravenously administered to TSE free VRQ/VRQ sheep, within five days following the blood collection. LD: leuco-depletion – LD/PR: leuco-depletion/Prion reduction. *:SEPACELL PURE RC (ASAHI). **: Plasma Filter Fenwal. ***: plasma for titration and cryoprecipitation study.</p

Composition of the 5 sheep whole blood pools used for preparation of labile blood products.

<p>Each pool was obtained by mixing 600–700 mL of whole blood collected in 3 VRQ/VRQ sheep orally inoculated with PG127 classical scrapie isolate. After blood collection (collection date) each donor was monitored till the occurrence of clinical signs. Donors were culled when displaying locomotor difficulties that could impair their abilities to feed (incubation period). TSE was confirmed by detection of abnormal PrP in lymphoid tissues (LRS) and central nervous system (CNS) using immunohistochemistry and Western Blot.</p

Efficacy of the Leuco-depletion and Leuco-depletion/Prion reduction filters on sheep Red Blood Cell concentrates.

<p>Each whole blood pool was constituted by mixing 600–700 mL from 3 VRQ/VRQ sheep orally inoculated with PG127 classical scrapie isolate. Aliquots of 400 mL of whole blood were processed to prepare Red Blood Cell concentrate (RBC). RBCs were then filtered using either a leuco-depletion filter (Sepacell pure RC –Asahi) or two Leucodepletion depletion/Prion reduction filters (LD/PR). Filtered RBC volumes varied between 155 and 190 mL.</p