George Garratty

Antibody against poly(ethylene glycol) adversely affects PEG‐asparaginase therapy in acute lymphoblastic leukemia patients

Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti‐PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti‐PEG was associated with rapid clearance PEG‐ASNase.

Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents

In contrast to the accepted general assumption that polyethylene glycol (PEG) is non-immunogenic and non-antigenic, animal studies clearly showed that uricase, ovalbumin and some other PEGylated agents can elicit antibody formation against PEG (anti-PEG). In humans, anti-PEG may limit therapeutic efficacy and/or reduce tolerance of PEG-asparaginase (PEG-ASNase) in patients with acute lymphoblastic leukemia and of pegloticase in patients with chronic gout, but did not impair hyposensitization of allergic patients with mPEG-modified ragweed extract or honeybee venom or the response to PEG-IFN in patients with hepatitis C. Of major importance is the recent finding of a 22 – 25% occurrence of anti-PEG in healthy blood donors, compared with a very low 0.2% occurrence two decades earlier. This increase may be due to an improvement of the limit of detection of antibodies during the years and to greater exposure to PEG and PEG-containing compounds in cosmetics, pharmaceuticals and processed food products. These results raise obvious concerns regarding the efficacy of PEG-conjugated drugs for a subset of patients. To address these concerns, the immunogenicity and antigenicity of approved PEGylated compounds should be carefully examined in humans. With all these data in hand, patients should be pre-screened and monitored for anti-PEG prior to and throughout a course of treatment with a PEGylated compound. Finally, protein conjugates with the poorly immunogenic hydroxy-PEG sequence or other hydrophilic polymers are in early phases of development and may represent an alternative to immunogenic PEGylated proteins.

Motivations to donate blood: demographic comparisons

BACKGROUND: Understanding blood donor motivations is crucial to improving effectiveness of donor recruitment and retention programs.

Drug-induced immune hemolytic anemia

Drug administration causes from 16 to 18 per cent of cases of acquired immune hemolytic anemia. The pathogenesis of erythrocyte sensitization by drug-related antibody with or without fixation of complement is variable, and there is a relationship between the responsible drug, the mechanism of red cell sensitization, clinical manifestations and laboratory methods of diagnosis. Drugs such as phenacetin and quinidine form a complex with the antidrug antibody, and the immune complex attaches to red cells usually fixing complement and causing acute intravascular hemolysis. Other drugs (e.g., penicillins), when given in large doses, coat normal red cells in vivo and in some patients a high titer IgG anti-drug antibody develops which reacts with the coated cells. Hemolytic anemia may develop with red cell destruction being primarily extravascular. Cephalosporins cause positive direct antiglobulin tests in a small percentage of patients either by the same mechanism as penicillins or by modification of the red cell membrane leading to nonimmunologic absorption of serum proteins. Hemolytic anemia has been reported only rarely. A few drugs (notably alpha methyldopa) cause the development of autoimmune hemolytic anemia. Knowledge of clinical manifestations and laboratory aids to diagnosis is necessary to distinguish immunohematologic abnormalities caused by drugs from other causes.

Blood group terminology 2004: from the International Society of Blood Transfusion committee on terminology for red cell surface antigens

1 Bristol Institute for Transfusion Sciences, Bristol, UK 2 Growing your Knowledge, Spit Junction, NSW, Australia 3 American Red Cross Blood Services, Los Angeles-Orange Counties Region, Los Angeles, CA, USA 4 Biotechnology Research Centre, Auckland University of Technology, Auckland, New Zealand 5 Regional Blood Transfusion Center, Department of Clinical Immunology, University Hospital, Arhus N, Denmark 6 Department of Pathology, University Hospitals UH-2G332, Ann Arbor, Michigan, USA 7 Reference Laboratory for Immunohematology and Blood Groups, National Blood Services Centre, Tel Hashomer, Israel 8 New York Blood Center, New York, NY, USA 9 Ortho-Clinical Diagnostics, Raritan, NJ, USA 10 Drexel University College of Medicine, Philadelphia, PA, USA 11 Gamma Biologicals Inc (subsidiary of Immunocor Inc), Houston, TX, USA 12 Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, the Netherlands 13 Centre national de Reference pour les Groupes sanguines (CNTS), Paris, France 14 International Blood Group Reference Laboratory, Bristol, UK 15 Finnish Red Cross Blood Transfusion Service, Helsinki, Finland 16 South African National Blood Service, East Coast Region, Pinetown, South Africa 17 Osaka Red Cross Blood Center, Osaka, Japan 18 Blood Bank, Hospital Sirio-Libanes, Sao Paulo, Brazil 19 Rh Laboratory, University of Manitoba, Winnipeg, Manitoba, Canada

Immune hemolytic anemia associated with drug therapy

Drug-induced immune hemolytic anemia (DIIHA) is rare; it can be mild or associated with acute severe hemolytic anemia (HA) and death. About 125 drugs have been implicated as the cause. The HA can be caused by drug-independent antibodies that are indistinguishable, in vitro and in vivo, from autoantibodies causing idiopathic warm type autoimmune hemolytic anemia (AIHA). More commonly, the antibodies are drug-dependent (i.e., will only react in vitro in the presence of the drug). The most common drugs to cause DIIHA are anti-microbials (e.g., cefotetan, ceftriaxone and piperacillin), which are associated with drug-dependent antibodies. The most common drug to cause AIHA is fludarabine. Finding out which drug is causing the problem and stopping that drug is the first approach to therapy. It is not easy to identify the drug interactions accurately in vitro; laboratories specializing in this area can be of great help.

The role of altruistic behavior, empathetic concern, and social responsibility motivation in blood donation behavior

BACKGROUND: Blood donation can be described as a prosocial behavior, and donors often cite prosocial reasons such as altruism, empathy, or social responsibility for their willingness to donate. Previous studies have not quantitatively evaluated these characteristics in donors or examined how they relate to donation frequency.

First year donation patterns predict long-term commitment for first-time donors

Background and Objectives  Converting first‐time donors to become regular donors continues to be a challenge facing blood centres. We examined whether first‐time donors with frequent return in the first 12 months were more likely to become regular donors.

First-time blood donors: demographic trends.

BACKGROUND: With changing demographics of the United States population and the continuous need to recruit new donors, it is important to monitor the demographic profile of first‐time donors and to evaluate changes in the donor pool to improve recruitment targeting.

International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Berlin report.

The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.