Hepatitis: Klein HG

Alter HJ, Klein HG. · Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA. · Blood. · Pubmed #18809775 No free full text.

Abstract: The beginning of the modern era of blood transfusion coincided with World War II and the resultant need for massive blood replacement. Soon thereafter, the hazards of transfusion, particularly hepatitis and hemolytic transfusion reactions, became increasingly evident. The past half century has seen the near eradication of transfusion-associated hepatitis as well as the emergence of multiple new pathogens, most notably HIV. Specific donor screening assays and other interventions have minimized, but not eliminated, infectious disease transmission. Other transfusion hazards persist, including human error resulting in the inadvertent transfusion of incompatible blood, acute and delayed transfusion reactions, transfusion-related acute lung injury (TRALI), transfusion-associated graft-versus-host disease (TA-GVHD), and transfusion-induced immunomodulation. These infectious and noninfectious hazards are reviewed briefly in the context of their historical evolution.

Klein HG, Spahn DR, Carson JL. · Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA. · Lancet. · Pubmed #17679019 No free full text.

Abstract: Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications.

Bryant BJ, Klein HG. · National Institutes of Health, Warren G. Magnuson Clinical Center, Department of Transfusion Medicine, 10 Center Dr, MSC-1184, Building 10, Room 1C711, Bethesda, MD 20894-1184, USA. · Arch Pathol Lab Med. · Pubmed #17488157 No free full text.

Abstract: CONTEXT: Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma fractionation and manufacturing industry, pathogen inactivation technologies have been successfully implemented resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US-licensed plasma derivatives since 1985. However, these technologies cannot be used to pathogen inactivate cellular blood components. Although current blood donor screening and disease testing has drastically reduced the incidence of transfusion-transmitted diseases, there still looms the threat to the blood supply of a new or reemerging pathogen. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection. OBJECTIVE: To review and summarize the principles, challenges, achievements, prospective technologies, and future goals of pathogen inactivation of the blood supply. DATA SOURCES: The current published English-language literature from 1968 through 2006 and a historical landmark article from 1943 are integrated into a review of this subject. CONCLUSIONS: The ultimate goal of pathogen inactivation is to maximally reduce the transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. This must be accomplished without introducing toxicities into the blood supply and without causing neoantigen formation and subsequent antibody production. Several promising pathogen inactivation technologies are being developed and clinically tested, and others are currently in use. Pathogen inactivation offers additional layers of protection from infectious agents that threaten the blood supply and has the potential to impact the safety of blood transfusions worldwide.

Klein HG. · Department of Medicine and Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA. · J Intern Med. · Pubmed #15715679 No free full text.

Abstract: The calculated residual infectious risk of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) from blood transfusion is extremely low. However, the risk of bacterial contamination remains and a variety of other agents including emerging viruses, protozoa and tick-borne agents threaten blood supplies and undermine public confidence in blood safety. Traditional methods of donor screening and testing have limited ability to further reduce disease transmission and cannot prevent an emerging infectious agent from entering the blood supply. Pathogen inactivation technologies have all but eliminated the infectious risks of plasma-derived protein fractions, but as yet no technique has proved sufficiently safe and effective for traditional blood components. Half-way technologies can reduce the risk of pathogen transmission from fresh frozen plasma and cryoprecipitate. Traditional methods of mechanical removal such as washing and filtration have limited success in reducing the risk of cell-associated agents, but methods aimed at sterilizing blood have either proved toxic to the cells or to the recipients of blood components. Several promising methods that target pathogen nucleic acid have recently entered clinical testing.