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Publications about the INTERCEPT Blood System for Platelets pathogen reduction system

Citation Topic
Mechanism of Action
Wollowitz S. Fundamentals of the psoralen-based Helinx technology for inactivation of infectious pathogens and leukocytes in platelets and plasma. Semin Hematol 2001;38:4-11. Mechanism of Action
In Vitro Pathogen Reduction – Bacteria
Lin, L  et al. Photochemical treatment of platelet concentrates with amotosalen and UVA inactivates a broad spectrum of pathogenic bacteria. Transfusion, 2004. 44: p. 1496 – 1504. Inactivation Data: In vitro study evaluating inactivation efficacy of INTERCEPT for high titers of bacteria. Following treatment, units were stored for 5 days under standard platelet storage conditions. No viable bacteria were detected in any treated unit after storage.
Schmidt, MS et al. Efficiency of the pathogen inactivation system INTERCEPT under experimental conditions. Vox Sang, 2011. 101(Suppl 1): p. 226. Inactivation Data: In vitro study evaluating inactivation efficacy of INTERCEPT for platelet units spiked with bacteria.
Nussbaumer, W et al. Prevention of transfusion of platelet components contaminated with low levels of bacteria: a comparison of bacteria culture and pathogen inactivation methods. Transfusion, 2007. 47(7): p. 1125-33. Inactivation Data: In vitro study evaluating inactivation efficacy of INTERCEPT for platelet units spiked with bacteria. Samples were monitored by culture for 5 days post-collection. Detection of bacteria in the untreated platelet units was variable at lower titers and required extended culture times for some strains. None of the INTERCEPT -treated units produced a positive culture result.
Schmidt, M et al. Evaluation of the effectiveness of a pathogen inactivation technology against clinically relevant transfusion-transmitted bacterial strains. Transfusion 2015 Sep;55(9):2104–12. Inactivation Data: In vitro study evaluating inactivation efficacy in whole blood, apheresis platelets, and buffy coat platelets spiked at two different concentrations and measured at two time points. Results demonstrate the need for minimal time period between blood donation and inactivation.
In Vitro Pathogen Reduction – Viruses
Lin, L et al. Inactivation of viruses in platelet concentrates by photochemical treatment with amotosalen and long-wavelength ultraviolet light. Transfusion, 2005. 45: p. 580-590. Inactivation Data: In vitro study evaluating efficacy of INTERCEPT for inactivation of viruses.
Roback, J. CMV Safety of Platelet Products: Comparison of Inactivation of INTERCEPT Blood System and Removal of Leukofiltration. Transfusion, 2007a. 47(S3): p. 23A. CMV In Vitro Study: No cell-free or cell-associated CMV was detected in a viral cell culture assay following INTERCEPT treatment, while CMV was detected leukoreduced components.
Roback, J. Inactivation of Infectious CMV in Platelet Products: Comparison of Inactivation of INTERCEPT Blood System and Leukofiltration. Blood, 2007b. 110(11): p. 849A. CMV In Vitro Study: No cell-free or cell-associated CMV was detected in a viral cell culture assay following INTERCEPT treatment, while CMV was detected in leukoreduced components.
Jordan, CT et al. Photochemical treatment of platelet concentrates with amotosalen hydrochloride and ultraviolet A light inactivates free and latent cytomegalovirus in a murine transfusion model. Transfusion, 2004. 44: p. 1159-1165. CMV In Vivo Study: INTERCEPT treatment of platelet concentrates prevented transfusion-transmitted CMV in an immune-compromised mouse model.
Lin, L. Inactivation of cytomegalovirus in platelet concentrates using HelinxTM technology. Semin Hematol, 2001. 38(4 Suppl 11): p. 27-33. CMV In Vivo Study: INTERCEPT treatment of platelet concentrates prevented transfusion-transmitted CMV in an immune-compromised mouse model.
Sawyer, L et al. Inactivation of influenza A H5N1 and Lymphocytic Choriomenigitis virus (LCMV) by the INTERCEPT Blood System (IBS). Transfusion, 2008. 48(2S): p. 88A. Emerging Pathogens: In vitro study evaluating inactivation efficacy of INTERCEPT for Influenza virus (H5N1).
Van Voorhis, WC, et al. Trypanosoma cruzi inactivation in human platelet concentrates and plasma by a psoralen (amotosalen HCl) and long-wavelength UV. Antimicrob Agents Chemother 2003;47(2): 475-9. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of T. cruzi (Chagas).
Dupuis, K, et al. High titers of dengue virus in platelet concentrates are inactivated by amotosalen and UVA light. Transfusion, 2012. 52((3S)): p. 225A. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of dengue virus.
Grellier, P et al. Photochemical inactivation with amotosalen and long-wavelength ultraviolet light of Plasmodium and Babesia in platelet and plasma components. Transfusion 2008;48(8): 1676-84. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of Plasmodium (malaria) and Babesia.
Tsetsarkin, KA et al. Photochemical Inactivation of Chikungunya Virus in Human Apheresis Platelet Components by Amotosalen and UVA Light. Am J Tropical Medicine and Hygiene 2013;88(6):1163-69. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of Chikungunya.
Eastman, RT et al, Leishmania inactivation in human pheresis platelets by a psoralen (amotosalen HCl) and long-wavelength ultraviolet irradiation. Transfusion, 2005. 45(9): p. 1459-63. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of Leishmania.
TA-GvHD and INTERCEPT
Grass, JA et al. Prevention of transfusion-associated graft-versus-host disease by photochemical treatment. Blood 1999;93(9):3140-3147. In vivo GVHD Study: Evaluation of the efficacy of INTERCEPT to prevent transfusion-associated graft-versus-host disease (TA-GVHD) in vivo using a well-characterized murine transfusion model.
Corash, L and L Lin, Novel processes for inactivation of leukocytes to prevent transfusion-associated graft-versus-host disease. Bone Marrow Transplantation, 2004. 33: p. 1-7. GVHD Review: Using a limiting dilution assay (LDA), the INTERCEPT Blood System demonstrates reduction of viable T-cells
Lin, L et al. Protection against TA-GVHD due to platelet transfusion by using pathogen inactivation with the INTERCEPT Blood System: gamma irradiation is not the only answer. Haematologica, 2010. 95 (Suppl 1): p. 230-237. GVHD review: Treatment results in approximately one amotosalen adduct per 83 base pairs, a sufficient frequency to ensure inactivation of most genes.
Hei, DJ, et al. Elimination of cytokine production in stored platelet concentrate aliquots by photochemical treatment with psoralen plus ultraviolet A light. Transfusion, 1999. 39: p. 239-48. In vitro GVHD Study: Cytokine production was substantially inhibited in the sample treated with INTERCEPT.
Clinical Trials, Observational Studies
Snyder, E et al. Recovery and Lifespan of 111 Indium radiolabeled platelets treated with pathogen inactivation using amotosalen HCl (S-59) and UVA light. Transfusion, 2004. 44: p. 1732-1440. Randomized, Controlled Clinical Study: Evaluated viability of INTERCEPT processed platelets in healthy subjects (recovery and survival).
Corash, L et al. S-59 clearance and kinetics after transfusion of platelets treated with Helinx™ Technology. Transfusion, 2000. 40(S10): p. 137. Randomized, Controlled Clinical Study: Evaluated clearance of residual amotosalen in healthy subjects.
McCullough, J et al. Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial. Blood, 2004. 104(5): p. 1534-41. Randomized, Controlled Clinical Study: SPRINT study. Evaluated safety, efficacy of INTERCEPT platelets. Primary endpoint was Grade 2 bleeding (primary endpoint met). (N=645)
Murphy, S et al. Platelet dose consistency and its effect on the number of platelet transfusions for support of thrombocytopenia: an analysis of the SPRINT trial of platelets photochemically treated with amotosalen HCl and ultraviolet A light. Transfusion. 2006 Jan;46(1):24-33. Follow Up Analysis for SPRINT Study: Analyzed platelet dose to determine the impact of the number of platelets transfused on transfusion requirements. Lower CIs and shorter transfusion intervals for INTERCEPT platelets suggest that platelet injury may occur during treatment; however, this injury does not result in a detectable increase in bleeding.
Slichter, SJ et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med, 2010. 362:600-613. Randomized, Controlled Clinical Study: (Not an INTERCEPT study) PLADO study. Evaluated platelet dose on bleeding in patients.
Corash, L et al. Determination of acute lung injury after repeated platelet transfusions. Blood. 2011 Jan 20;117(3):1014-20. SPRINT retrospective re-analysis (most recent publication): No difference was found between the treated and untreated groups with regard to acute lung injury (ALI), including ARDs (discrepancy likely due to different diagnosis criteria used for ALI).
Snyder, E et al. Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial. Transfusion, 2005. 45(12):1864-75. SPRINT retrospective re-analysis: No difference was found between the treated and untreated groups with regard to acute lung injury (ALI), including ARDs (discrepancy likely due to different diagnosis criteria used for ALI).
Janetzko, K et al. Therapeutic efficacy and safety of photochemically treated apheresis platelets processed with an optimized integrated set. Transfusion, 2005. 45(9):1443-1452. Randomized, Controlled Clinical Study: Evaluated safety, efficacy of INTERCEPT platelets. Primary endpoint was 1 hr platelet count increment (primary endpoint met). (N=43)
van Rhenen, D J et al. Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial. Blood, 2003. 101:2426-2433. Randomized, Controlled Clinical Study: EuroSprite study. Evaluated safety, efficacy of INTERCEPT platelets. Primary endpoint was 1 hr platelet count increment (primary endpoint met). (N=103)
Slichter, SJ et al. Platelets photochemically treated with amotoslaen HCl and ultraviolet A light correct prolonged bleeding times in thrombocytopenic patients. Transfusion, 2006. 46:731-740. Randomized, Controlled Clinical Study: Evaluated safety, efficacy of INTERCEPT platelets. Primary endpoint was bleeding time (primary endpoint met). (N=32)
Schlenke, P et al. Safety and clinical efficacy of platelet components prepared with pathogen inactivation in routine use for thrombocytopenic patients. Ann Hematol, 2011. 90(12):1457-65. Observational Study: Evaluated frequency of acute transfusion reactions in routine setting. (N=51)
Infanti, L et al. Pathogen-inactivation of platelet components with the INTERCEPT Blood System : a cohort study. Transfus Apher Sci, 2011. 45(2):175-81. Observational Study: Evaluated frequency of acute transfusion reactions in routine setting. (N=46)
Platelet Hemovigilance
Knutson, F et al. A prospective, active haemovigilance study with combined cohort analysis of 19,175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment. Vox Sang 2015 May 15. doi:10.1111/vox.12287 [Epub ahead of print]. Platelets – Routine Use: Hemovigilance study evaluating 4,067 patients receiving 19,175 platelet transfusions over 7 years, in 21 centres, across 11 countries.
Osselaer, JC et al. An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment. Vox Sang, 2008. 94(4):315-23. Platelets – Routine Use: Active hemovigilance study evaluating the routine use of INTERCEPT platelets.
Osselaer, JC et al. A prospective observational cohort safety study of 5106 platelet transfusions with components prepared with photochemical pathogen inactivation treatment. Transfusion, 2008. 48(6):1061-71. Platelets – Routine Use: Hemovigilance study evaluating the routine use of INTERCEPT platelets.
Osselaer, JC et al. Universal adoption of pathogen inactivation of platelet components: impact on platelet and red blood cell component use. Transfusion, 2009. 49(7):1412-22. Platelets – Routine Use: Hemovigilance study evaluating the routine use of INTERCEPT platelets.
Cazenave, J et al. Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period. Transfusion, 2011. 51(3):622-9. Platelets – Routine Use: Hemovigilance study evaluating the routine use of INTERCEPT platelets in France.
Cazenave, JP, H Isola, et al., Pathogen Inactivation of Platelets, in Platelet Transfusion Therapy, J.D. Sweeney and M. Lozano, Editors. 2013, AABB Press: Bethesda, MD.119-176. Platelets – Routine Use: National hemovigilance study evaluating the routine use of INTERCEPT platelets in France.
Toxicity Studies
Ciaravino, V et al. Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 AND UVA treated) platelets. Human and Experimental Toxicology, 2001. 20:533-550. Toxicity: Animal studies (rats, dogs) evaluating toxicology and kinetics of INTERCEPT.
Ciaravino, V et al. Assessment of safety in neonates for transfusion of platelets and plasma prepared with amotosalen photochemical pathogen inactivation treatment by a 1-month intravenous toxicity study in neonatal rats. Transfusion 2009; 49:985–994. Toxicity: Studies conducted in neonatal rats to evaluate the safety of INTERCEPT-treated blood components for neonates. No reproductive or developmental toxicities observed.
Tice, RR et al. The pathogen reduction treatment of platelets with S-59 HCl (Amotosalen) plus ultraviolet A light: genotoxicity profile and hazard assessment. Mutation Research 2007;630:50-68. Toxicity: Reviews the genotoxicity profile of INTERCEPT, and assesses the mutagenic and carcinogenic hazards in recipients of treated components. No genotoxicity or mutagenicity observed.
Other
AABB, Standards for Blood Banks and Transfusion Services, in Process Control 2014, AABB: Bethesda, MD. AABB Standard 5.1.5.1. “Blood bank or transfusion service shall have methods to limit and to detect or inactivate bacterial contamination in all platelet components.”

Publications about the INTERCEPT Blood System for Plasma pathogen reduction system

Citation Topic
Mechanism of Action
Wollowitz S. Fundamentals of the psoralen-based Helinx technology for inactivation of infectious pathogens and leukocytes in platelets and plasma. Semin Hematol 2001;38:4-11. Mechanism of Action
In Vitro Inactivation Data
Singh, Y et al. Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function. Transfusion 2006;46(7): 1168-77. Plasma – Inactivation Data, Coagulation Function: In vitro studies evaluating inactivation efficacy of INTERCEPT for viruses, bacteria, protozoa, and effect on plasma function.
Sawyer, L et al. Inactivation of Transfusion-Transmitted Vector Borne Pathogens. Vox Sang 2009;96(Suppl 1):233-234. Emerging Pathogens: In vitro studies evaluating inactivation efficacy of INTERCEPT for vector-borne pathogens such as WNV, Chikungunya, Plasmodium, T. cruzi.
Sawyer, L et al. Inactivation of Influenza A H5N1 and Lymphocytic Choriomeningitis Virus (LCMV) by the INTERCEPT Blood System (IBS). Transfusion 2008;48 (S1);88A. Emerging Pathogens: In vitro study evaluating inactivation efficacy of INTERCEPT for Influenza virus (H5N1).
Van Voorhis, WC et al. Trypanosoma cruzi inactivation in human platelet concentrates and plasma by a psoralen (amotosalen HCl) and long-wavelength UV. Antimicrob Agents Chemother 2003;47(2): 475-9. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of Chikungunya. 
Grellier, P et al. Photochemical inactivation with amotosalen and long-wavelength ultraviolet light of Plasmodium and Babesia in platelet and plasma components. Transfusion 2008;48(8): 1676-84. Emerging Pathogens: In vitro study evaluating efficacy of INTERCEPT for inactivation of Plasmodium (malaria) and Babesia.
Clinical Trials
Hambleton, J et al. Pharmacokinetic study of FFP photochemically treated with amotosalen (S-59) and UV light compared to FFP in healthy volunteers anticoagulated with warfarin. Transfusion 2002;42:1302–1307

2 Prospective Clinical Studies:

  • Evaluated tolerability, safety, amotosalen clearance after transfusion of INTERCEPT plasma to healthy subjects. (N=15)
  • Evaluated transfusion of INTERCEPT plasma to healthy subjects anticoagulated with warfarin sodium. (N=27)
de Alarcon, P et al. Fresh frozen plasma prepared with amotosalen HCl (S-59) photochemical pathogen inactivation: transfusion of patients with congenital coagulation factor deficiencies. Transfusion 45(8): 1362-72.

2 Prospective Clinical Studies:

  • Transfusion of INTERCEPT plasma to patients with multiple coagulation factor deficiencies evaluated. (N=13)
  • Transfusion of INTERCEPT plasma to patients with congenital coagulation factor deficiencies conducted in multicenter study. (N=34)
Mintz, PD et al. A randomized, controlled Phase III trial of therapeutic plasma exchange with fresh-frozen plasma (FFP) prepared with amotosalen and ultraviolet A light compared to untreated FFP in thrombotic thrombocytopenic purpura. Transfusion 2006; 46:1693–1704 Prospective Clinical Study: Transfusion of INTERCEPT plasma to patients with TTP by therapeutic plasma exchange studied. (N=35)
Mintz, PD et al. Photochemically treated fresh frozen plasma for transfusion of patients with acquired coagulopathy of liver disease. Blood 2006; 107:3753–3760. Prospective Clinical Study: Transfusion of INTERCEPT plasma to patients with acquired coagulopathy due to liver disease with/without liver transplantation assessed.(N=121)
Cinqualbre, J et al. Comparative effectiveness of plasma prepared with amotosalen-UVA pathogen inactivation and conventional plasma for support of liver transplantation. Transfusion 2015 Jul;55(7):1710-20. Retrospective Clinical Study: Post-marketing experience with transfusion of INTERCEPT plasma to patients undergoing liver transplant. (N=174)
Herbrecht, R et al. Comparative Effectiveness of Plasma Prepared with Pathogen Inactivation (INTERCEPT™) and Quarantine Plasma (PFCs) for Therapeutic Plasma Exchange of Patients with Thrombotic Thrombocytopenic Purpura. Vox Sang 2012;103(S1):245. Retrospective Clinical Study:Post-marketing experience with transfusion of INTERCEPT plasma to patients with TTP evaluated. (N=31)
Cinqualbre, J et al. Comparative Effectiveness of Plasma Prepared with Pathogen Inactivation (INTERCEPT™) and Quarantine for Support of Liver Transplantation. Vox Sang 2012;103(S2):247-248. Retrospective Clinical Study:Post-marketing experience with transfusion of INTERCEPT plasma to patients undergoing liver transplant assessed. (N=328)
Plasma Hemovigilance
Bost, V et al. Independent evaluation of tolerance of therapeutic plasma inactivated by amotosalen-HCI-UVA (INTERCEPT™) over a 5-year period of extensive delivery. Vox Sang 2015 May 29. doi:10.1111/vox.12300. [Epub ahead of print] Emerging Pathogens: Hemovigilance study evaluating routine use of INTERCEPT plasma in 15,133 transfusions.
Cazenave, JP et al. An active hemovigilance program characterizing the safety profile of 7,483 transfusions with plasma components prepared with amotosalen and UVA photochemical treatment. Transfusion 2010;50:1210-1219. Plasma – Routine Use: Active hemovigilance study evaluating the routine use of INTERCEPT plasma in France.
Bost, V et al. A regional haemovigilance retrospective study of four types of therapeutic plasma in a ten-year survey period in France. Vox Sanguinis 2013;104:337-341. Plasma – Routine Use: Retrospective hemovigilance study evaluating the routine use of INTERCEPT plasma in France.
Toxicity Studies
Ciaravino, V et al. Preclinical safety profile of plasma prepared using the INTERCEPT Blood System. Vox Sang 2003; 85:171–182. Toxicity: The studies of general toxicology, safety pharmacology, phototoxicity, reproductive toxicity and venous irritation, summarized in this review.
Ciaravino, V et al. Assessment of safety in neonates for transfusion of platelets and plasma prepared with amotosalen photochemical pathogen inactivation treatment by a 1-month intravenous toxicity study in neonatal rats. Transfusion 2009; 49:985–994. Toxicity: Studies conducted in neonatal rats to evaluate the safety of INTERCEPT-treated blood components for neonates.
Other
Hawkins BM et al. Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review. Transfusion 48(2): 382-392. Review that suggests that cardiac abnormalities may be important and often unrecognized causes of mortality and morbidity in patients with TTP.