Lily Lin

Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light

BACKGROUND: A photochemical treatment process has been developed for the inactivation of viruses and bacteria in platelet concentrates. This process is based on the photochemical reaction of a novel psoralen, S‐ 59, with nucleic acids upon illumination with long‐wavelength ultraviolet light (UVA, 320–400 nm). STUDY DESIGN AND METHODS: High levels of pathogens were added to single‐donor platelet concentrates containing 3 to 5 × 10(11) platelets in 300 mL of 35‐percent autologous plasma and 65‐percent platelet additive solution. After treatment with S‐59 (150 microM) and UVA (0–3 J/cm2), the infectivity of each pathogen was measured with established biologic assays. In vitro platelet function after photochemical treatment was evaluated during 7 days of storage by using a panel of 14 assays. The in vivo recovery and life span of photochemically treated platelets were evaluated after 24 hours of storage in a primate transfusion model. RESULTS: The following levels of pathogen inactivation were achieved:>10(6.7) plaque‐forming units (PFU) per mL of cell‐free human immunodeficiency virus (HIV),>10(6.6) PFU per mL of cell‐associated HIV,>10(6.8) infectious dose (ID50) per mL of duck hepatitis B virus (a model for hepatitis B virus),>10(6.5) PFU per mL of bovine viral diarrhea virus (a model for hepatitis C virus),>10(6.6) colony‐forming units of Staphylococcus epidermidis, and>10(5.6) colony‐forming units of Klebsiella pneumoniae. Expression of integrated HIV was inhibited by 0.1 microM S‐ 59 and 1 J per cm2 of UVA. In vitro and in vivo platelet function were adequately maintained after antiviral and antibacterial treatment. CONCLUSION: Photochemical treatment of platelet concentrates offers the potential for reducing transfusion‐related viral and bacterial diseases.

Photochemical treatment of platelet concentrates with amotosalen and long-wavelength ultraviolet light inactivates a broad spectrum of pathogenic bacteria

BACKGROUND:u2002 Bacterial contamination of platelet (PLT) concentrates can result in transfusion‐transmitted sepsis. A photochemical treatment (PCT) process with amotosalen HCl and long‐wavelength ultraviolet light (UVA), which cross‐links nucleic acids, was developed to inactivate bacteria and other pathogens in PLT concentrates.

Inactivation of viruses in platelet concentrates by photochemical treatment with amotosalen and long-wavelength ultraviolet light.

BACKGROUND: Viral contamination of platelet (PLT) concentrates can result in transfusion‐transmitted diseases. A photochemical treatment (PCT) process with amotosalen‐HCl and long‐wavelength ultraviolet light (UVA), which cross‐links nucleic acids, was developed to inactivate viruses and other pathogens in PLT concentrates.

Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function

BACKGROUND:u2002 The INTERCEPT Blood System, a photochemical treatment (PCT) process, has been developed to inactivate pathogens in platelet concen‐trates. These studies evaluated the efficacy of PCT to inactivate pathogens in plasma and the effect of PCT on plasma function.

Photochemical inactivation of bacteria and HIV in buffy-coat-derived platelet concentrates under conditions that preserve in vitro platelet function

Background and Objectives: A photochemical process has been tested for the inactivation of viruses and bacteria in buffy‐coat derived platelet concentrates (BC PCs). Materials and Methods: BC PCs in 35% CPD plasma and 65% platelet‐additive solution (PAS III) were exposed to photochemical treatment (PCT) with 150 μM of the psoralen S‐59 and a 3 J/cm2 treatment with longwavelength ultraviolet light (UVA, 320–400 nm). Platelet function was evaluated following PCT using a panel of in vitro assays. Results: This PCT process was highly effective at inactivating gram‐positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis) and gram‐negative bacteria (Enterobacter aerogenes, Pseudomonas aeruginosa, Serratia marcescens). No viable bacteria were detected following PCT and 7 days of platelet storage while bacterial growth was detected in paired untreated control BC PCs. Complete inactivation of the gram‐positive Bacillus cereus was achieved only in one of two replicate experiments with BC PCs. PCT was also highly effective for inactivation of human immunodeficiency virus HIV‐1 in BC PCs inoculated with approximately 106 tissue culture infectious doses per milliliter (TCID5n/ml) of cell‐associated HIV‐1. Rapid inactivation was observed with increasing UVA doses: with 150 μM S‐59 and a 1 J/cm2 treatment of UVA, a reduction of 5:6±0.5 log TCID50/ml was achieved, and a reduction of >6.4 log TCID50/ml was achieved with 150 μM S‐59 and a 3 J/cm2 treatment of UVA. No physiologically relevant differences in platelet functions were found between the test and the control BC PCs during 7 days of storage. Conclusion: PCT with 150 μM S‐59 and a 3 J/cm2 UVA treatment does not adversely affect in vitro properties of BC PCs stored at 22°C for 7 days. The PCT process inactivated bacteria and HIV‐1 inoculated into the BC PCs. These results extend the earlier reported efficacy of PCT apheresis PCs to BC PCs.

Pathogen Inactivation of Platelet and Plasma Blood Components for Transfusion Using the INTERCEPT Blood System

Background: The transmission of pathogens via blood transfusion is still a major threat. Expert conferences established the need for a pro-active approach and concluded that the introduction of a pathogen inactivation/reduction technology requires a thorough safety profile, a comprehensive pre-clinical and clinical development and an ongoing hemovigilance program. Material and Methods: The INTERCEPT Blood System utilizes amotosalen and UVA light and enables for the treatment of platelets and plasma in the same device. Preclinical studies of pathogen inactivation and toxicology and a thorough program of clinical studies have been conducted and an active hemovigilance-program established. Results: INTERCEPT shows robust efficacy of inactivation for viruses, bacteria (including spirochetes), protozoa and leukocytes as well as large safety margins. Furthermore, it integrates well into routine blood center operations. The clinical study program demonstrates the successful use for very diverse patient groups. The hemovigilance program shows safety and tolerability in routine use. Approximately 700,000 INTERCEPT-treated products have been transfused worldwide. The system is in clinical use since class III CE-mark registration in 2002. The safety and efficacy has been shown in routine use and during an epidemic. Conclusion: The INTERCEPT Blood System for platelets and plasma offers enhanced safety for the patient and protection against transfusion-transmitted infections.

Transfusion of platelet components prepared with photochemical pathogen inactivation treatment during a Chikungunya virus epidemic in Ile de La Réunion

BACKGROUND: During the Chikungunya virus (CHIKV) epidemic on Ile de La Réunion, France, more than 30% of 750,000 inhabitants were infected. Local blood donation was suspended to prevent transfusion‐transmitted infection (TT‐CHIKV). To sustain the availability of platelet (PLT) components, the Établissement Français du Sang implemented universal pathogen inactivation (INTERCEPT, Cerus Europe BV) of PLT components (CPAs). The study assessed the safety of PLT components treated with pathogen inactivation transfused in routine clinical practice.

Recovery and life span of 111indium-radiolabeled platelets treated with pathogen inactivation with amotosalen HCl (S-59) and ultraviolet A light

BACKGROUND:u2002 A photochemical treatment (PCT) method to inactivate pathogens in platelet concentrates has been developed. The system uses a psoralen, amotosalen HCl, coupled with ultraviolet A (UVA) illumination.

Universal adoption of pathogen inactivation of platelet components: impact on platelet and red blood cell component use.

BACKGROUND: Pathogen inactivation of platelet (PLT) components (INTERCEPT Blood System, Cerus Europe) was implemented into routine practice at a blood center supporting a tertiary care hospital. Utilization of platelet components (PCs) and red blood cell (RBC) components was analyzed for 3 years before and 3 years after introduction of pathogen inactivation to assess the impact of pathogen inactivation on component use.

A multi-centre study of therapeutic efficacy and safety of platelet components treated with amotosalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion.

Bacteria in platelet components (PC) may result in transfusion‐related sepsis (TRS). Pathogen inactivation of PC with amotosalen (A‐PC) can abrogate the risk of TRS and hence facilitate storage to 7u2003d. A randomized, controlled, double‐blinded trial to evaluate the efficacy and safety of A‐PC stored for 6–7u2003d was conducted. Patients were randomized to receive one transfusion of conventional PC (C‐PC) or A‐PC stored for 6–7u2003d. The primary endpoint was the 1u2003h corrected count increment (CCI) with an acceptable inferiority of 30%. Secondary endpoints included 1‐ and 24‐h count increment (CI), 24‐h CCI, time to next PC transfusion, red blood cell (RBC) use, bleeding and adverse events. 101 and 100 patients received A‐PC or C‐PC respectively. The ratio of 1‐h CCI (A‐PC:C‐PC) was 0·87 (95% confidence interval: 0·73, 1·03) demonstrating non‐inferiority (Pu2003=u20030·007), with respective mean 1‐h CCIs of 8163 and 9383; mean 1‐h CI was not significantly different. Post‐transfusion bleeding and RBC use were not significantly different (Pu2003=u20030·44, Pu2003=u20030·82 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2·2 vs. 2·3u2003d, Pu2003=u20030·72). Storage of A‐PCs for 6–7u2003d had no impact on platelet efficacy.