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1
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Puliyanda DP, Jordan SC. Management of the sensitized pediatric renal transplant candidate. Pediatr Transplant 2024; 28:e14694. [PMID: 38400645 DOI: 10.1111/petr.14694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 12/14/2023] [Accepted: 01/05/2024] [Indexed: 02/25/2024]
Abstract
Kidney transplantation is the treatment of choice for patients with ESRD as it is associated with improved patient survival and better quality of life, especially in children. There are several barriers to a successful transplant including organ shortage, anatomic barriers, and immunologic barriers. One of the biggest immunologic barriers that precludes transplantation is sensitization, when patients have antibodies prior to transplantation, resulting in positive crossmatches with donor. 30%-40% of adult patients on the wait list are sensitized. There is a growing number of pediatric patients on the wait list who are sensitized. This poses a unique challenge to the pediatric transplant community. Therefore, attempts to perform desensitization to remove or suppress pathogenic HLA antibodies resulting in acceptable crossmatches, and ultimately a successful transplant, while reducing the risk of acute rejection, are much needed in these children. This review article aims to address the management of such patients both prior to transplantation, with strategies to overcome sensitization, and after transplantation with monitoring for allograft rejection and other complications.
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Affiliation(s)
- Dechu P Puliyanda
- Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Stanley C Jordan
- Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
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2
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Hill M, Iro M, Sadarangani M, Absoud M, Cantrell L, Chong K, Clark C, Easton A, Gray V, Kneen R, Lim M, Liu X, Pike M, Solomon T, Vincent A, Willis L, Yu LM, Pollard AJ. Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial. BMJ Open 2023; 13:e072134. [PMID: 37945292 PMCID: PMC10649701 DOI: 10.1136/bmjopen-2023-072134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 09/29/2023] [Indexed: 11/12/2023] Open
Abstract
OBJECTIVE To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. DESIGN Phase 3b multicentre, double-blind, randomised placebo-controlled trial. SETTING Twenty-one hospitals in the UK. PARTICIPANTS Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308. INTERVENTION Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment. MAIN OUTCOME MEASURE The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended. SECONDARY OUTCOME MEASURES The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data. RESULTS 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG. CONCLUSIONS The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis. TRIAL REGISTRATION NUMBER Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925.
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Affiliation(s)
- Matilda Hill
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
| | - Mildred Iro
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
| | - Manish Sadarangani
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Department of Paediatrics, University of Oxford, Oxford, UK
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Michael Absoud
- Children's Neurosciences, Evelina London Children's Hospital Neurosciences Department, London, UK
- Department of Womens and Childrens Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Liberty Cantrell
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
| | - Kling Chong
- UCL Great Ormond Street Institute of Child Health, London, UK
| | | | - Ava Easton
- The Encephalitis Society, Malton, North Yorkshire, UK
- Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK
| | - Victoria Gray
- Clinical Health Psychology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
| | - Rachel Kneen
- Department of Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Ming Lim
- Children's Neurosciences, Evelina London Children's Hospital Neurosciences Department, London, UK
- Department of Womens and Childrens Health, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Xinxue Liu
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
| | - Michael Pike
- Department of Paediatric Neurology, Oxford University Hospitals NHS Trust, Oxford, UK
| | - Tom Solomon
- Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
- National Institute for Health Research Health Protection Research Unit in Emerging Zoonotic Infections, University of Liverpool, Liverpool, UK
- Walton Centre NHS Foundation Trust, Liverpool, UK
- The Pandemic Institute, Liverpool, UK
| | - Angela Vincent
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
| | - Louise Willis
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
| | - Ly-Mee Yu
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Andrew J Pollard
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK
- Department of Paediatrics, University of Oxford, Oxford, UK
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3
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Hou YB, Chang S, Chen S, Zhang WJ. Intravenous immunoglobulin in kidney transplantation: Mechanisms of action, clinical applications, adverse effects, and hyperimmune globulin. Clin Immunol 2023; 256:109782. [PMID: 37742791 DOI: 10.1016/j.clim.2023.109782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/11/2023] [Accepted: 09/20/2023] [Indexed: 09/26/2023]
Abstract
Intravenous immunoglobulin (IVIG) has been developed for over 40 years. The mechanisms of action of IVIG are complex and diverse, and there may be multiple mechanisms that combine to influence it. IVIG has been used in kidney transplantation for desensitization, treatment of antibody-mediated rejection, and ABO-incompatible transplantation. and treatment or prevention of some infectious diseases. Hyperimmune globulins such as cytomegalovirus hyperimmune globulin (CMV-IG) and hepatitis B hyperimmune globulin (HBIG) have also been used to protect against cytomegalovirus and hepatitis B virus, respectively. However, IVIG is also associated with some rare but serious adverse effects and some application risks, and clinicians need to weigh the pros and cons and develop individualized treatment programs to benefit more patients. This review will provide an overview of the multiple mechanisms of action, clinical applications, adverse effects, and prophylactic measures of IVIG, and hyperimmune globulin will also be introduced in it.
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Affiliation(s)
- Yi-Bo Hou
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China
| | - Sheng Chang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China
| | - Song Chen
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China
| | - Wei-Jie Zhang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.
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4
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Routray SS, Tripathy S, Ray GK. Hemolysis in reverse grouping: Evaluation and implication of high titer isoagglutinin of two blood donors. Asian J Transfus Sci 2023; 17:288-290. [PMID: 38274977 PMCID: PMC10807518 DOI: 10.4103/ajts.ajts_165_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/20/2023] [Accepted: 03/19/2023] [Indexed: 01/27/2024] Open
Abstract
Hemolysis is a positive agglutination reaction and is primarily associated with high anti-A or anti-B antibody titers. This high titer may result in no agglutination due to the "prozone" phenomenon. Platelet concentrate of high titer has an adverse effect on the recipient of the non-identical ABO blood group. Similarly, the blood products with higher titers of isoagglutinin have recently increased the incidence of intravenous immunoglobulins-related hemolysis. In this Asian subcontinent, the impact of O blood donors with high antibody titers or ABO incompatible platelets is hardly addressed. Blood was collected from two healthy donors and subjected to blood grouping as done routinely. Hemolysis was observed in the reverse grouping with the "B-"cell. Blood grouping was repeated with the conventional tube technique (CTT) where there was no agglutination with the "B"-cell. Suspecting the "prozone" phenomenon, serial dilution of anti-B was done by CTT, and the titer was found to be 1:256 and 1:128 in both cases. Then, the reverse grouping was repeated with a diluted serum (1:8), and the blood group was confirmed to be A RhD-positive and O RhD-positive, respectively. The absence of agglutination in a reverse grouping is not only an indicator of weak antibody but also a presentation of the "prozone" phenomenon. This could be differentiated by doing the titer of isoagglutinin. Hemolysis due to high agglutinin levels should be documented and evaluated, and blood components should be properly labeled to ensure that the product is transfused to the same blood group patients.
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Affiliation(s)
- Suman Sudha Routray
- Department of Immunohematology and Blood Transfusion, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Sukanta Tripathy
- Department of Immunohematology and Blood Transfusion, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Gopal Krushna Ray
- Department of Immunohematology and Blood Transfusion, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
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5
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Ucar İ, Koyuncu MB, Solmaz AA, Ugurludogan AC, Mercan S, Kucuk M, Unal T, Mazman S, Atilla E. Don't neglect the rare adverse event with intravenous immunoglobulin: Hemolytic anemia. Transfus Clin Biol 2023; 30:11-15. [PMID: 36028153 DOI: 10.1016/j.tracli.2022.08.144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 08/18/2022] [Accepted: 08/19/2022] [Indexed: 02/07/2023]
Abstract
Intravenous immunoglobulin (IVIG) associated hemolytic anemia is an under-recognized complication of IVIG therapy. The incidence of this adverse event is not clear. Patients at high risk for IVIG-associated hemolytic anemia include non-O blood group recipients and those undergoing high-dose administration for inflammatory or autoimmune disorders. Here, two different cases of IVIG-associated hemolytic anemia are demonstrated. The first patient, a 66 year-old male with Guillain-Barré syndrome, had a severe attack for which erythrocyte replacement was required. Mild hemolysis was detected during IVIG administration in the second patient, a 57 year-old female with chronic immune thrombocytopenic purpura. Following IVIG termination, the hemolysis diminished gradually. Although it is rare and often manageable, clinicians should be aware of and monitor patients for hemolytic anemia following IVIG therapy.
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Affiliation(s)
- İsmail Ucar
- Mersin City Hospital, Department of Rhemautology, Turkey
| | | | | | | | | | | | - Tufan Unal
- Mersin City Hospital, Blood Bank, Turkey
| | - Semir Mazman
- Mersin City Hospital, Department of Neurology, Turkey
| | - Erden Atilla
- Mersin City Hospital, Department of Hematology, Turkey.
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6
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Frutos MÁ, Crespo M, Valentín MDLO, Alonso-Melgar Á, Alonso J, Fernández C, García-Erauzkin G, González E, González-Rinne AM, Guirado L, Gutiérrez-Dalmau A, Huguet J, Moral JLLD, Musquera M, Paredes D, Redondo D, Revuelta I, Hofstadt CJVD, Alcaraz A, Alonso-Hernández Á, Alonso M, Bernabeu P, Bernal G, Breda A, Cabello M, Caro-Oleas JL, Cid J, Diekmann F, Espinosa L, Facundo C, García M, Gil-Vernet S, Lozano M, Mahillo B, Martínez MJ, Miranda B, Oppenheimer F, Palou E, Pérez-Saez MJ, Peri L, Rodríguez O, Santiago C, Tabernero G, Hernández D, Domínguez-Gil B, Pascual J. Recommendations for living donor kidney transplantation. Nefrologia 2022; 42 Suppl 2:5-132. [PMID: 36503720 DOI: 10.1016/j.nefroe.2022.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 10/26/2021] [Indexed: 06/17/2023] Open
Abstract
This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.
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Affiliation(s)
| | - Marta Crespo
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | | | | | - Juana Alonso
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | | | - Esther González
- Nephrology Department, Hospital Universitario 12 Octubre, Spain
| | | | - Lluis Guirado
- Nephrology Department, Fundacio Puigvert, Barcelona, Spain
| | | | - Jorge Huguet
- RT Surgical Team, Fundació Puigvert, Barcelona, Spain
| | | | - Mireia Musquera
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | - David Paredes
- Donation and Transplantation Coordination Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Ignacio Revuelta
- Nephrology and RT Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Antonio Alcaraz
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Manuel Alonso
- Regional Transplantation Coordination, Seville, Spain
| | | | - Gabriel Bernal
- Nephrology Department, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - Alberto Breda
- RT Surgical Team, Fundació Puigvert, Barcelona, Spain
| | - Mercedes Cabello
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | - Joan Cid
- Apheresis and Cell Therapy Unit, Haemotherapy and Haemostasis Department, Hospital Clinic Universitari, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and RT Department, Hospital Clinic Universitari, Barcelona, Spain
| | - Laura Espinosa
- Paediatric Nephrology Department, Hospital La Paz, Madrid, Spain
| | - Carme Facundo
- Nephrology Department, Fundacio Puigvert, Barcelona, Spain
| | | | | | - Miquel Lozano
- Apheresis and Cell Therapy Unit, Haemotherapy and Haemostasis Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | | | | | | | - Eduard Palou
- Immunology Department, Hospital Clinic i Universitari, Barcelona, Spain
| | | | - Lluis Peri
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | | | | | - Domingo Hernández
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain.
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7
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Recomendaciones para el trasplante renal de donante vivo. Nefrologia 2022. [DOI: 10.1016/j.nefro.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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8
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Koo Y, Yun T, Chae Y, Lee D, Choi D, Oh J, Kim J, Kim H, Yang MP, Kang BT. Suspected human intravenous immunoglobulin-induced acute haemolytic anaemia in a dog. J Small Anim Pract 2021; 63:482-485. [PMID: 34874062 DOI: 10.1111/jsap.13449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 10/18/2021] [Accepted: 10/31/2021] [Indexed: 11/28/2022]
Abstract
A 2-year-old mixed breed dog presented with a 1-year history of crust and erosion on the nasal planum. Because histopathological examination revealed ruptured intraepidermal pustules and superficial dermal inflammation, the dog was diagnosed with pemphigus foliaceus. Human intravenous immunoglobulin was administered in two consecutive doses of 0.5 g/kg/day due to poor therapeutic response to previous immunosuppressive therapy. From Day 3 after the first dose of human intravenous immunoglobulin, tachypnoea, pale mucous membrane, haemoglobinuria and haemoglobinemia were observed, thus confirming haemolytic anaemia. Other drug-induced haemolytic anaemias were excluded because no additional drugs had been administered before the haemolysis occurred. Immune-mediated haemolytic anaemia was also excluded because the direct antiglobulin test was negative. Two transfusions were performed, and haemolysis was not observed from Day 4 of haemolytic anaemia onset. In conclusion, human intravenous immunoglobulin-induced haemolytic anaemia should be considered in dogs that develop haemolysis following the administration of human intravenous immunoglobulin.
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Affiliation(s)
- Y Koo
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - T Yun
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Y Chae
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - D Lee
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - D Choi
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - J Oh
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - J Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - H Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - M P Yang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - B T Kang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
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9
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Treatment-associated hemolysis in Kawasaki disease: association with blood-group antibody titers in IVIG products. Blood Adv 2021; 4:3416-3426. [PMID: 32722782 DOI: 10.1182/bloodadvances.2020002253] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 06/18/2020] [Indexed: 12/20/2022] Open
Abstract
Hemolytic anemia resulting from IV Immunoglobulin (IVIG) treatment can be a serious complication, especially for those with underlying conditions with a high level of inflammation and after administration of high IVIG dosages, such as Kawasaki disease (KD), a multisystem vasculitis affecting young children. This hemolysis is caused by antibodies against blood groups A and B, but the precise mechanism for hemolysis is not known. We performed a single center, partly retrospective, partly prospective study of a cohort of 581 patients who received IVIG for treatment of KD from 2006 to 2013. Factors associated with hemolysis were identified through univariable and multivariable logistic regression. Six IVIG preparations were assayed for their hemolytic effect with serological and cellular assays to clarify the mechanism of red cell destruction. During the study period, a sudden increase in the incidence of hemolysis was observed, which coincided with the introduction of new IVIG preparations in North America that contained relatively high titers of anti-A and anti-B. These blood-group-specific antibodies were of the immunoglobulin G2 (IgG2) subclass and resulted in phagocytosis by monocyte-derived macrophages in an FcγRIIa-dependent manner. Phagocytosis was increased in the presence of proinflammatory mediators that mimicked the inflammatory state of KD. An increased frequency of severe hemolysis following IVIG administration was caused by ABO blood-group-specific IgG2 antibodies leading to FcγRIIa-dependent clearance of erythrocytes. This increase in adverse events necessitates a reconsideration of the criteria for maximum titer (1:64) of anti-A and anti-B in IVIG preparations.
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10
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Implications of Fc Neonatal Receptor (FcRn) Manipulations for Transplant Immunotherapeutics. Transplantation 2020; 104:17-23. [PMID: 31397806 DOI: 10.1097/tp.0000000000002912] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Alloimmune injury to allografts is mediated by pathogenic donor-specific alloantibodies, usually of the IgG isotype. Currently, strategies used to reduce donor-specific alloantibodies are collectively called desensitization. Despite successes, these treatments have limited efficacy and can be associated with adverse events, infectious complications, and high cost. Fc neonatal receptor (FcRn) was originally discovered as a transport mechanism for IgG from maternal circulation to fetus. FcRn receptors are now known to be widely distributed in virtually all tissues. IgG and albumin binding to FcRn is pH-dependent, which results in a significant prolongation their half-life. Structural analysis shows FcRn is a nonclassical major histocompatibility complex Class I receptor, which is emerging as a novel target to significantly reduce the half-life of pathogenic antibodies or extend the half-life of therapeutic monoclonals. Manipulation of IgG-Fc/FcRn interactions has implications for treatment of virtually all IgG-mediated diseases. The use of monoclonals directed at the FcRn can rapidly enhance the turnover of total IgG, including pathogenic IgG. In this review, we highlight the aspects of FcRn biology responsible for development of FcRn targeted therapeutics aimed at pathogenic autoantibodies and alloantibodies. We also explore the novel modifications of therapeutic monoclonals that exploit FcRn functions to enhance therapeutic efficacy.
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11
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Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible kidney transplantation. World J Transplant 2020; 10:191-205. [PMID: 32844095 PMCID: PMC7416363 DOI: 10.5500/wjt.v10.i7.191] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 05/17/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
One of the principal obstacles in transplantation from living donors is that approximately 30% are immunologically incompatible because of the presence in the recipient of antibodies directed against the human leukocyte antigen system of the donor or because of the incompatibility of the ABO system. The aim of this review is to describe the more recent data from the literature on the different protocols used and the clinical outcomes of ABO-incompatible kidney transplantation. Two different strategies are used to overcome these barriers: desensitization of the recipient to remove the antibodies and to prevent their rebound after transplantation and the exchange of organs between two or more pairs. The largest part of this review is dedicated to describing the techniques of desensitization. Even if the first reports of successful renal transplantation between ABO-incompatible pairs have been published by 1980, the number of ABO-incompatible transplants increased substantially in this century because of our improved knowledge of the immune system and the availability of new drugs. Rituximab has substantially replaced splenectomy. The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects. Recent reports document outcomes for such transplantation similar to the outcomes of standard transplantation.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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12
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Wallenhorst C, Patel A, Shebl A, Hubsch A, Simon TL, Martinez C. Anti-A/B isoagglutinin reduction in an intravenous immunoglobulin product and risk of hemolytic anemia: a hospital-based cohort study. Transfusion 2020; 60:1381-1390. [PMID: 32488887 PMCID: PMC7496198 DOI: 10.1111/trf.15859] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/03/2020] [Accepted: 04/08/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Intravenous immunoglobulins (IVIG) are derived from large human plasma pools. IVIG-associated hemolytic anemia (HA) is a known class effect, likely attributed to dose-dependent passive transfer of anti-A/B isoagglutinins. Two isoagglutinin reduction steps were implemented in the manufacturing process of Privigen (human 10% liquid IVIG): exclusion of high-anti-A-titer donors in 2013, replaced by specific immunoaffinity chromatography in 2015. We aim to estimate the clinical effectiveness of both measures. STUDY DESIGN AND METHODS Using the US hospital-based Premier Healthcare Database, three Privigen cohorts were generated based on calendar periods indicative of manufacturing changes: Period 1 (baseline) January 2008 to December 2012, Period 2 (high-anti-A-titer donor exclusion) October 2013 to December 2015, and Period 3 (immunoaffinity chromatography) October 2016 to April 2019. HA within a 10-day at-risk period after Privigen administrations was identified from review of patient record summaries. Incidence rate ratios (IRRs) were estimated from Poisson regression (Period 1 reference) adjusting for hospital setting, sex, age, Privigen indication, dose, and first use. RESULTS Crude incidence rates of HA were 1.49 per 10,000 person-days in Period 1 (38 HA, 9439 patients), 1.01 in Period 2 (20 HA, 7710 patients), and 0.14 in Period 3 (3 HA, 7759 patients). Adjusted IRR for HA in Period 2 was 0.71 (95% confidence interval [CI], 0.41-1.23), and in Period 3 was 0.10 (0.03-0.33) compared with Period 1. The IRR for HA in Period 3 compared with Period 2 was 0.14 (95% CI, 0.04-0.47). CONCLUSION Implementation of immunoaffinity chromatography in Privigen manufacturing resulted in a significant 90% reduction of HA risk. HA has become a rare event in association with Privigen use.
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Affiliation(s)
| | - Ami Patel
- CSL Behring LLC, King of Prussia, Pennsylvania, USA
| | | | | | | | - Carlos Martinez
- Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt, Germany
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13
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Shebl A, Gabriel S, Van Dinther K, Hubsch A, Lawo JP, Hoefferer L, Welsh S. Isoagglutinin reduction in intravenous immunoglobulin (IgPro10, Privigen) by specific immunoaffinity chromatography reduces its reporting rates of hemolytic reactions: an analysis of spontaneous adverse event reports. Transfusion 2020; 60:1278-1286. [PMID: 32410287 PMCID: PMC7383922 DOI: 10.1111/trf.15846] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 04/01/2020] [Accepted: 04/02/2020] [Indexed: 01/24/2023]
Abstract
BACKGROUND Hemolysis is an infrequent but recognized and potentially serious adverse effect of intravenous immunoglobulin (IVIG). Relatively elevated hemolysis reporting rates were seen with some IVIG products with high anti-A/B isoagglutinin content, among which IgPro10 (Privigen, CSL Behring). For IgPro10, two isoagglutinin reduction measures were successively implemented: 1) anti-A donor screening and 2) immunoaffinity chromatography (IAC; Ig IsoLo)-based isoagglutinin reduction step included in the production process. The aim of this analysis was to investigate the effects of these isoagglutinin reduction measures on the reporting rates of IgPro10 hemolysis worldwide. STUDY DESIGN AND METHODS Between February 2008 and December 2018, hemolysis reports from the CSL Behring Global Safety Database were analyzed in relationship to changes in IVIG IgPro10 production methods. Further analysis classified hemolysis reports by indication and blood group. RESULTS Median (minimum-maximum) anti-A/anti-B titers were 32 (8-64)/16 (8-32) at baseline, 32 (8-64)/16 (8-32) after donor screening, and 8 (8-32)/4 (2-8) after implementation of IAC. The reporting rate of hemolytic reactions per 1000 kg IgPro10 sold was 4.05 cases at baseline, 2.00 after donor screening, and 0.50 after implementation of IAC. In 2018, there were seven reports of hemolytic reactions; representing 0.18 cases per 1000 kg IgPro10 sold, with a reduction of 95.6% versus baseline. CONCLUSION Following implementation of the IAC isoagglutinin reduction step, spontaneous reports of hemolytic events with IgPro10 were significantly and consistently reduced versus IgPro10 without isoagglutinin reduction, offering patients a more favorable benefit-risk profile.
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Affiliation(s)
| | | | | | | | | | | | - Susan Welsh
- CSL Behring, King of Prussia, Pennsylvania, USA
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14
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Abstract
Sensitization to human leukocyte antigens (HLAs) has been one of the major clinical challenges for successful kidney transplantation. In end-stage renal disease, kidney transplantation provides benefits compared with dialysis in terms of improved patient survival better quality of life, and lower ongoing costs after the first year. Living donor kidney transplantation has an advantage with improved allograft survival, and performed earlier and electively compared with deceased donor transplantation. However sensitized patients are increasing in number on transplant waiting lists, and their prospect of getting a transplant is less than nonsensitized patients due to immunological incompatibility with the donor. Strategy for sensitized patients are listing for a compatible deceased donor transplant or, if they have a living donor, either selecting a kidney exchange program or undergoing a desensitization procedure. Desensitization procedures may be undertaken to increase access to either living or deceased donor transplants, and in some situations may also be employed to facilitate participation in a kidney exchange, in less immunological barrier to be overcome. The question of whether individuals are better off with a desensitization treatment followed by HLA-incompatible living donor transplantation or waiting on the deceased donor kidney transplant list for a compatible transplant has recently been addressed by two large multicenter studies, with conflicting results. A multicenter study from the United States published in the New England Journal of Medicine [365;318 326.2011] concluded that there was a strong survival benefit for sensitized patients undergoing desensitization followed by HLA-incompatible living donor kidney transplant compared with those remaining on the waiting list. Of interest, a second study, published in the Lancet, [389;727 734.2017] found no significant survival advantage for desensitized patients compared with similar patients remaining on the waiting list in the United Kingdom. Controversies still remain regarding how desensitization can be achieved and which techniques are effective and safe. In this chapter various complications from the desensitization will be dealt with in current use of medications or armamentum.
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15
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Keh R, Kahlil A, Nihoyannopoulos L, Compton L, Kapoor M, Gosal D, Manji H, Rossor A, Reilly M, Lunn M, Lavin T, Carr A. Routine blood monitoring in maintenance immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant? J Neurol Sci 2020; 408:116527. [DOI: 10.1016/j.jns.2019.116527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 09/21/2019] [Accepted: 10/08/2019] [Indexed: 01/01/2023]
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16
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Figgins BS, Aitken SL, Whited LK. Optimization of intravenous immune globulin use at a comprehensive cancer center. Am J Health Syst Pharm 2019; 76:S102-S106. [DOI: 10.1093/ajhp/zxz233] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Abstract
Purpose
Intravenous immune globulin (IVIG) is a high-cost medication used in a diverse range of settings. At many institutions, IVIG is dosed using total body weight (TBW). Recent evidence suggests that alternative dosing weights reduce waste without compromising clinical outcomes. The objective of this study was to quantify the waste reduction potential generated through the use of alternative IVIG dosing weights.
Methods
We performed a retrospective analysis of all IVIG doses administered from January 2011 through January 2016 to adults (≥18 years). TBW and height at the time of administration were used to calculate prescribed dose (g/kg), ideal body weight (IBW), and adjusted body weight (AdjBW). Three dosing methods were analyzed, as follows: use of AdjBW if TBW is >120% IBW (method 1), AdjBW for all doses (method 2), and IBW for all doses (method 3). Outcomes included potential IVIG use averted, direct drug cost savings, and reductions in outpatient infusion times for each method.
Results
A total of 9,918 doses were administered to 2,564 patients over 5 years, representing an average usage of 75,994 g/year. If dosing methods 1, 2, and 3 had been used, the annual use of IVIG would have decreased by 21.9% (16,658 g/year, p < 0.001), 24.2% (18,371 g/year, p < 0.001), and 35.9% (27,252 g/year, p < 0.001), respectively. This translates into average annual cost differences of $2.37 million, $2.62 million, and $3.89 million and average annual outpatient infusion time savings of 841 hours, 920 hours, and 1,366 hours, respectively.
Conclusion
IVIG dosing optimization through use of alternative dosing weights represents a significant source of waste reduction and cost reduction.
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Affiliation(s)
- Bradley S Figgins
- Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Samuel L Aitken
- Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Laura K Whited
- Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX
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17
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Abbas A, Rajabally YA. Complications of Immunoglobulin Therapy and Implications for Treatment of Inflammatory Neuropathy: A Review. Curr Drug Saf 2019; 14:3-13. [PMID: 30332974 DOI: 10.2174/1574886313666181017121139] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 10/11/2018] [Accepted: 10/12/2018] [Indexed: 11/22/2022]
Abstract
BACKGROUND Intravenous Immunoglobulin (IVIg) forms a cornerstone of effective treatment for acute and chronic inflammatory neuropathies, with a class I evidence base in Guillain-Barré Syndrome (GBS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). It is generally considered to be a safe therapy however there are several recognised complications which are reviewed in this article. DISCUSSION AND CONCLUSION Most adverse events are immediate and mild such as headache, fever and nausea although more serious immediate reactions such as anaphylaxis may rarely occur. Delayed complications are rare but may be serious, including thromboembolic events and acute kidney injury, and these and associated risk factors are also discussed. We emphasise the importance of safe IVIg administration and highlight practical measures to minimise complications of this therapy.
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Affiliation(s)
- Ahmed Abbas
- Department of Neurophysiology, Queen Elizabeth Hospital, University Hospital of Birmingham, Birmingham, United Kingdom
| | - Yusuf A Rajabally
- Department of Neurophysiology, Queen Elizabeth Hospital, University Hospital of Birmingham, Birmingham, United Kingdom.,Department of Neurology, Queen Elizabeth Hospital, University Hospital of Birmingham, Birmingham, United Kingdom.,Department of Aston Brain Centre, Aston University, Birmingham, United Kingdom
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18
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Taylor AS, Cooling L, Yamada C. ABO-associated antibody-mediated rejection following A2B-to-B renal transplantation and successful treatment with therapeutic plasma exchange. Transfusion 2019; 59:1883-1885. [PMID: 31050827 DOI: 10.1111/trf.15201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 01/15/2019] [Accepted: 01/20/2019] [Indexed: 11/28/2022]
Affiliation(s)
- Alexander S Taylor
- Transfusion Medicine/Department of Pathology, University of Michigan, Ann Arbor, MI
| | - Laura Cooling
- Transfusion Medicine/Department of Pathology, University of Michigan, Ann Arbor, MI
| | - Chisa Yamada
- Transfusion Medicine/Department of Pathology, University of Michigan, Ann Arbor, MI
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19
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Mangiola M, Marrari M, Ensor C, Spycher MO, Berger M, Zeevi A. Therapeutic Human IgG Preparations Contain Mixture of HLA Antibodies to Native HLA Antigens and Cryptic Epitopes With Little Clinical Significance. Transplantation 2019; 102:2126-2132. [PMID: 29877923 DOI: 10.1097/tp.0000000000002312] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Human immunoglobulins (H-Ig) are widely used in solid organ transplantation for immunoglobulin G (IgG) replacement and for desensitization and treatment of antibody-mediated rejection. They are obtained from plasma pools and may contain HLA antibodies that can be detrimental to transplant recipients. The goal of this study was to evaluate HLA antibodies in multiple lots of 2 commercial H-Ig preparations by Luminex single-antigen bead (SAB) and cell-based crossmatch assays. METHODS Thirty lots of 2 commercial H-Ig products (CSL Behring, King of Prussia, PA) were evaluated: 6 Hizentra and 24 Privigen. All were adsorbed and diluted 1:10 before testing. HLA IgG antibodies were determined by 2 Luminex SAB kits and C1q screen for complement-binding capability. Lots were tested for the presence of antibody to denatured vs. intact class I HLA alleles using acid-treated SAB. Surrogate T and B-cell flow cytometry crossmatches (FCXM) were performed with peripheral blood lymphocytes from 2 healthy donors. RESULTS Twenty-two (73%) lots at 1:10 showed SAB reactivity with mean fluorescent intensity of 2000 or greater for HLA class I, 67% (20/30 lots) for class II. The reactivity pattern was similar using both SAB kits. Acid treatment revealed antibodies to denatured class I: the majority of HLA-C, half of HLA-B and few HLA-A alleles. No C1q reactivity was observed. Surrogate flow cytometry crossmatch results were positive (>150 median channel shift), but were fourfold to eightfold lower than expected. CONCLUSIONS The H-Ig products tested consisted of low titer, non-complement-binding HLA class I and class II antibodies; most of the observed class I HLA reactivity was toward denatured HLA antigens.
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Affiliation(s)
- Massimo Mangiola
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Marilyn Marrari
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Christopher Ensor
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.,Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA
| | | | | | - Adriana Zeevi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
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20
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21
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Lioger B, Maillot F, Ternant D, Passot C, Paintaud G, Bejan-Angoulvant T. Efficacy and Safety of Anti-D Immunoglobulins versus Intravenous Immunoglobulins for Immune Thrombocytopenia in Children: Systematic Review and Meta-analysis of Randomized Controlled Trials. J Pediatr 2019; 204:225-233.e8. [PMID: 30314658 DOI: 10.1016/j.jpeds.2018.07.065] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 07/11/2018] [Accepted: 07/13/2018] [Indexed: 01/19/2023]
Abstract
OBJECTIVES To compare the efficacy and safety of intravenous immunoglobulins (IVIG) and anti-D immunoglobulin (anti-D) in pediatric immune thrombocytopenia (ITP). STUDY DESIGN We conducted a systematic review and meta-analysis following PRISMA guidelines, including all randomized controlled trials that have assessed the efficacy and safety of anti-D and IVIG in children with ITP. We searched Medline, Embase, and Cochrane databases. Primary outcomes were the proportion of children achieving platelet count responses as defined in each study and bleeding response. Other safety outcomes included infusion reactions and hemolysis. RESULTS Eleven studies with 558 children were included. Anti-D was significantly inferior to IVIG at increasing platelet counts, both for thresholds of >20 × 109/L at 24-72 hours (response rate ratio for anti-D vs IVIG: 0.85, 95% CI 0.78-0.94) and >50 × 109/L at 24-72 hours (response rate ratio for anti-D vs IVIG: 0.75, 95% CI 0.61-0.92). Bleeding response was assessed in 4 studies, but some heterogeneity in reporting leads to unclear conclusion. General symptoms after anti-D infusion were less frequent than after IVIG (Peto OR 0.39, 95% CI 0.25-0.62). Hemolysis was more frequent after anti-D. The overall quality of the studies was low. CONCLUSIONS Compared with anti-D, IVIG led to a better response in terms of platelet count and may be preferred as a first-line treatment of ITP in children with acute hemorrhagic symptoms. However, the clinical significance of IVIG superiority on platelet count remains unclear.
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Affiliation(s)
- Bertrand Lioger
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Service de Médecine Interne, Tours, France.
| | - François Maillot
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; Université François-Rabelais de Tours, INSERM 1069, Tours, France
| | - David Ternant
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Laboratoire de Pharmacologie-Toxicologie, Tours, France
| | - Christophe Passot
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Laboratoire de Pharmacologie-Toxicologie, Tours, France
| | - Gilles Paintaud
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Laboratoire de Pharmacologie-Toxicologie, Tours, France
| | - Theodora Bejan-Angoulvant
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Service de Pharmacologie Clinique, Tours, France
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22
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Lim AKH, Kansal A, Kanellis J. Factors associated with anaemia in kidney transplant recipients in the first year after transplantation: a cross-sectional study. BMC Nephrol 2018; 19:252. [PMID: 30290796 PMCID: PMC6173839 DOI: 10.1186/s12882-018-1054-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Accepted: 09/24/2018] [Indexed: 11/13/2022] Open
Abstract
Background Anaemia after kidney transplantation may reduce quality of life, graft or patient survival. We aimed to determine the prevalence and risk factors for anaemia in the initial 12 months after transplantation. Methods We conducted a cross-sectional study at 6 and 12 months after transplantation. Anaemia was defined by World Health Organization criteria taking into consideration erythropoietin use. Logistic regression was used to determine the association between demographic, clinical and pharmacological risk factors for the main outcome of moderate-severe anaemia. Results A total of 336 transplant recipients were included and the prevalence of moderate-severe anaemia was 27.4% at 6 months and 15.2% at 12 months. Lower kidney function, female gender, transferrin saturation below 10% and proteinuria were associated with moderate-severe anaemia at both time points. Recent intravenous immunoglobulin treatment was associated with anaemia at 6 months. Recent infection and acute rejection were also associated with anaemia 12 months. Around 20% of patients had at least one blood transfusion but they were uncommon beyond 3 months. Conclusions Anaemia remains highly prevalent requiring treatment with erythropoietin and transfusions. Most identifiable risk factors relate to clinical problems rather than pharmacological management, while markers of iron-deficiency remain difficult to interpret in this setting. Electronic supplementary material The online version of this article (10.1186/s12882-018-1054-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Andy K H Lim
- Department of Nephrology, Monash Health, Clayton, Victoria, 3168, Australia. .,Department of Medicine, Monash University, Clayton, Victoria, 3168, Australia.
| | - Arushi Kansal
- Department of Nephrology, Monash Health, Clayton, Victoria, 3168, Australia
| | - John Kanellis
- Department of Nephrology, Monash Health, Clayton, Victoria, 3168, Australia.,Department of Medicine, Monash University, Clayton, Victoria, 3168, Australia
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23
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Nolan BE, Wang Y, Pary PP, Luban NLC, Wong ECC, Ronis T. High-dose intravenous immunoglobulin is strongly associated with hemolytic anemia in patients with Kawasaki disease. Transfusion 2018; 58:2564-2571. [PMID: 30265742 DOI: 10.1111/trf.14879] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 05/03/2018] [Accepted: 05/04/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hemolysis is a reported side effect of intravenous immunoglobulin (IVIG) therapy in adults, but pediatric data are scarce. We determined the frequency of IVIG-associated hemolysis in patients with Kawasaki disease (KD) and characterized risk factors for hemolysis. We hypothesized that hemolysis is more common in children with KD than adults with other disorders, and hemolysis risk is related to IVIG dose and degree of inflammation. STUDY DESIGN AND METHODS This was an 8-year, single-center, retrospective cohort study. A total of 419 KD patients were identified; 123 had pre- and post-treatment complete blood counts allowing for assessment of anemia. Hemolytic anemia was defined as decrease in hemoglobin after IVIG greater than 1 g/dL with immunohematologic or biochemical studies supporting hemolysis. RESULTS 123 patients were stratified as having hemolysis (n = 18, 15%) or nonhemolysis (n = 105, 85%). Patients with hemolysis were more likely to have complete versus incomplete KD (65% vs. 39%, p = 0.04) and refractory versus nonrefractory course (78% vs. 16%, p < 0.001). Patients receiving 4 g/kg versus 2 g/kg IVIG were more likely to hemolyze (89% vs. 34%, p < 0.001). Patients with hemolysis had mostly non-O blood group (94%), positive direct antiglobulin tests (89%), and positive eluates (72%). Two-thirds of patients with hemolysis required RBC transfusion. CONCLUSIONS Hemolysis occurred in 15% of KD patients evaluated for anemia and is strongly associated with high-dose (4 g/kg) IVIG. KD patients receiving high-dose IVIG should have close hematologic monitoring to identify hemolysis.
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Affiliation(s)
| | - Yunfei Wang
- Center for Translational Science, Washington, DC
| | - Philippe P Pary
- Division of Laboratory Medicine, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC
| | - Naomi L C Luban
- Department of Pediatrics, Washington, DC.,Center for Translational Science, Washington, DC.,Division of Laboratory Medicine, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC.,Division of Hematology, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC.,Department of Pathology, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC
| | - Edward C C Wong
- Department of Pediatrics, Washington, DC.,Center for Translational Science, Washington, DC.,Division of Laboratory Medicine, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC.,Division of Hematology, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC.,Department of Pathology, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC
| | - Tova Ronis
- Department of Pediatrics, Washington, DC.,Center for Translational Science, Washington, DC.,Division of Rheumatology, Center for Cancer and Blood Disorders, George Washington School of Medicine and Health Sciences, Children's National Health System, Washington, DC
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24
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Technological Aspects of Ensuring the Specific Safety of Human Immunoglobulin and Albumin Preparations. Pharm Chem J 2018. [DOI: 10.1007/s11094-018-1842-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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25
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Chu Z, Zou W, Xu Y, Sun Q, Zhao Y. The regulatory roles of B cell subsets in transplantation. Expert Rev Clin Immunol 2018; 14:115-125. [PMID: 29338551 DOI: 10.1080/1744666x.2018.1426461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Zhulang Chu
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Department of Pathology, Beijing University of Chinese Medicine, Beijing, China
| | - Weilong Zou
- Surgery of Transplant and Hepatopancrobiliary, The General Hospital of Chinese People’s Armed Police Forces, Beijing, China
| | - Yanan Xu
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Qiquan Sun
- Department of Renal Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yong Zhao
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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26
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Ha KS, Jang GY, Lee J, Lee KC, Son CS. Laboratory Markers in Incomplete Kawasaki Disease according to Coronary Artery Outcome. Korean Circ J 2018; 48:287-295. [PMID: 29625511 PMCID: PMC5889978 DOI: 10.4070/kcj.2017.0342] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/27/2017] [Accepted: 01/17/2018] [Indexed: 11/30/2022] Open
Abstract
Background and Objectives We defined laboratory marker profiles typical of incomplete Kawasaki disease (iKD) during illness, especially with respect to the presence of a coronary artery abnormality such as coronary artery dilation or aneurysm. Methods This retrospective study examined the clinical and laboratory markers of patients with iKD over time, along with those of patients with complete KD (cKD) and febrile controls. Results Of 795 patients, 178 had iKD, 504 had cKD and 113 were febrile controls. During the transition from the acute to subacute phase, the age-adjusted hemoglobin levels and platelet counts were significantly lower and higher, respectively, in the subacute phase than in the acute phase in both iKD and cKD patients, which differed from those of febrile controls. Lower levels of acute and subacute age-adjusted hemoglobin levels in iKD patients (odds ratio [OR], 0.538 and 0.583; p=0.006 and 0.018, respectively) and higher subacute platelet counts in cKD patients (OR, 1.004; p=0.014) were correlated with the risk of coronary dilation. A higher acute neutrophil-to-lymphocyte ratio was associated with aneurysm only in cKD patients (OR, 1.059; p=0.044). Conclusions The iKD patients share KD-specific laboratory marker profiles in terms of complete blood cell counts and acute phase reactant levels with cKD patients. However, the factors predicting coronary dilation differ according to the phenotype; lower acute and subacute age-adjusted hemoglobin levels predict coronary dilation only in iKD patients.
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Affiliation(s)
- Kee Soo Ha
- Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea
| | - Gi Young Jang
- Department of Pediatrics, Korea University Ansan Hospital, Seoul, Korea
| | - JungHwa Lee
- Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea.
| | - Kwang Chul Lee
- Department of Pediatrics, Korea University Anam Hospital, Seoul, Korea
| | - Chang Sung Son
- Department of Pediatrics, Korea University Anam Hospital, Seoul, Korea
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27
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Cicha A, Fischer MB, Wesinger A, Haas S, Bauer WM, Wolf HM, Sauerwein KMT, Reininger B, Petzelbauer P, Pehamberger H, Handisurya A. Effect of intravenous immunoglobulin administration on erythrocyte and leucocyte parameters. J Eur Acad Dermatol Venereol 2017; 32:1004-1010. [PMID: 29114967 DOI: 10.1111/jdv.14671] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 10/20/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Intravenous immunoglobulins (IVIG) are an attractive therapeutic tool for therapy of toxic epidermal necrolysis and severe forms of certain autoimmune diseases, including dermatomyositis, autoimmune blistering diseases, systemic vasculitis and lupus erythematodes. OBJECTIVES Prompted by a case of IVIG-associated haemolytic anaemia, the effects of IVIG administrations on haematological parameters in patients with dermatological conditions were investigated. METHODS Erythrocyte and leucocyte parameters were retrospectively analysed in 16 patients who had received IVIG at doses from 1 to 3 g/kg bodyweight (n = 35 cycles). The influence of IVIG on leucocyte survival was determined in vitro. RESULTS Decreased absolute erythrocyte numbers, haemoglobin and haematocrit levels and a case of haemolytic anaemia were linked to transfusion of high-, but not low-dose IVIG. In contrast, leucopenia post-IVIG occurred in the vast majority of the recipients, unrelated to the administered IVIG amounts. In vitro investigations revealed a dose-dependent impairment of cell survival by IVIG in the neutrophil and monocyte, but not in the lymphocyte subpopulations. In several IVIG preparations, substantial amounts of blood group anti-A/anti-B antibodies were detected which could have accounted for the observed changes in the haematological parameters in our study cohort. CONCLUSIONS IVIG products should be administered strictly according to indications. Commercially available IVIG products can contain blood group-specific antibodies that may induce haemolysis in some recipients. Monitoring of blood counts during applied IVIG therapy, especially when high doses are administered, is recommended.
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Affiliation(s)
- A Cicha
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - M B Fischer
- Department of Health Science and Biomedicine, Danube University Krems, Krems an der Donau, Austria.,Department of Transfusion Medicine, Medical University of Vienna, Vienna, Austria
| | - A Wesinger
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - S Haas
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - W M Bauer
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - H M Wolf
- Immunology Outpatient Clinic, Vienna, Austria.,Medical School, Sigmund Freud University Vienna, Vienna, Austria
| | | | - B Reininger
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - P Petzelbauer
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - H Pehamberger
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - A Handisurya
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
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28
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Sridhar G, Ekezue BF, Izurieta HS, Forshee RA, Selvam N, Mintz PD, Anderson SA, Menis MD. Occurrence of hemolytic reactions on the same day as immune globulin product administrations during 2008 to 2014. Transfusion 2017; 58:70-80. [DOI: 10.1111/trf.14384] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 08/24/2017] [Accepted: 08/24/2017] [Indexed: 11/26/2022]
Affiliation(s)
| | | | - Hector S. Izurieta
- Center for Biologics Evaluation and Research, U.S. Food and Drug Administration; Silver Spring Maryland
| | - Richard A. Forshee
- Center for Biologics Evaluation and Research, U.S. Food and Drug Administration; Silver Spring Maryland
| | | | - Paul D. Mintz
- Center for Biologics Evaluation and Research, U.S. Food and Drug Administration; Silver Spring Maryland
| | - Steven A. Anderson
- Center for Biologics Evaluation and Research, U.S. Food and Drug Administration; Silver Spring Maryland
| | - Mikhail D. Menis
- Center for Biologics Evaluation and Research, U.S. Food and Drug Administration; Silver Spring Maryland
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29
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Mielke O, Fontana S, Goranova-Marinova V, Shebl A, Spycher MO, Wymann S, Durn BL, Lawo JP, Hubsch A, Salama A. Hemolysis related to intravenous immunoglobulins is dependent on the presence of anti-blood group A and B antibodies and individual susceptibility. Transfusion 2017; 57:2629-2638. [PMID: 28840942 DOI: 10.1111/trf.14289] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 06/14/2017] [Accepted: 06/25/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients treated with intravenous immunoglobulins (IVIG) rarely experience symptomatic hemolysis. Although anti-A and anti-B isoagglutinins from the product are involved in most cases, the actual mechanisms triggering hemolysis are unclear. STUDY DESIGN AND METHODS A prospective, open-label, multicenter, single-arm clinical trial in 57 patients with immune thrombocytopenia treated with IVIG (Privigen, CSL Behring) was conducted. RESULTS Twenty-one patients received one infusion (1 g/kg) and 36 received two infusions (2 × 1 g/kg) of IVIG. After a study duration of more than 2 years, no cases of clinically significant hemolysis as defined in the protocol were identified. Data of patients with mild hematologic and biochemical changes were analyzed in more detail. Twelve cases (10/23 patients with blood group A1 and 2/11 patients with blood group B, all having received 2 g/kg IVIG) were adjudicated as mild hemolysis (median hemoglobin [Hb] decrease, -3.0 g/dL); Hb decreases were transient, with partial or full recovery achieved by last visit. Eighteen patients (31.6%), all with non-O blood group, of whom 16 (88.9%) received 2 g/kg IVIG, fulfilled post hoc criteria for hemolytic laboratory reactions. Red blood cell (RBC) eluates of all direct antiglobulin test-positive samples were negative for non-ABO blood group antibodies. Blood groups A and B antigen density on RBCs appeared to be a risk factor for hemolytic laboratory reactions. Platelet response to treatment was observed in 42 patients (74%); eight of 12 patients with complete response had blood group A1. CONCLUSION Isoagglutinins are involved in clinically nonsignificant hemolysis after treatment with IVIG, but individual susceptibility varies greatly.
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Affiliation(s)
| | - Stefano Fontana
- Interregional Blood Transfusion Service SRC, Bern, Switzerland
| | | | | | | | | | | | | | | | - Abdulgabar Salama
- Institut für Transfusionsmedizin, Charité-Universitätsmedizin Berlin, Berlin, Germany
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30
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Prise en charge des événements indésirables chez les patients sous traitement par immunoglobulines : recommandations pour la pratique clinique. Rev Med Interne 2017; 38:312-319. [DOI: 10.1016/j.revmed.2016.10.390] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 09/25/2016] [Accepted: 10/20/2016] [Indexed: 12/29/2022]
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31
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Severe Hemolytic Anemia Following Intravenous Immunoglobulin in an Infant With Kawasaki Disease. J Pediatr Hematol Oncol 2017; 39:e100-e102. [PMID: 27879540 DOI: 10.1097/mph.0000000000000704] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Severe hemolytic anemia (HA) is an uncommon adverse reaction of intravenous immunoglobulin (IVIg) administration. Previous reports assume that antibodies contained in IVIg preparations are the cause of hemolysis. We report a 10-month-old infant with Kawasaki disease who was treated with high-dose IVIg and developed severe HA. The patient's Rh blood type was D+C+c+E-e+. He developed anti-C and anti-e antibodies following treatment with IVIg, and, after considering all possible causes of hemolysis, we concluded that this was a case of autoimmune HA induced by immunoglobulin treatment. The hyperinflammatory condition associated with Kawasaki disease may have contributed to the severity of anemia.
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32
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Reduction of Isoagglutinin in Intravenous Immunoglobulin (IVIG) Using Blood Group A- and B-Specific Immunoaffinity Chromatography: Industry-Scale Assessment. BioDrugs 2017; 30:441-451. [PMID: 27646589 PMCID: PMC5054059 DOI: 10.1007/s40259-016-0192-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Hemolysis, a rare but potentially serious complication of intravenous immunoglobulin (IVIG) therapy, is associated with the presence of antibodies to blood groups A and B (isoagglutinins) in the IVIG product. An immunoaffinity chromatography (IAC) step in the production process could decrease isoagglutinin levels in IVIG. OBJECTIVES Our objectives were to compare isoagglutinin levels in a large number of IVIG (Privigen®) batches produced with or without IAC and to assess the feasibility of the production process with an IAC step on an industrial scale. METHODS The IAC column comprised a blend of anti-A and anti-B resins formed by coupling synthetic blood group antigens (A/B-trisaccharides) to a base bead matrix, and was introduced towards the end of the industrial-scale IVIG manufacturing process. Isoagglutinin levels in IVIG were determined by anti-A and anti-B hemagglutinin direct and indirect methods according to the European Pharmacopoeia (Ph. Eur.) and an isoagglutinin flow cytometry assay. IVIG product quality was assessed with respect to the retention of immunoglobulin G (IgG) subclasses, specific antibodies, and removal of IgM using standardized procedures. RESULTS The IAC step reduced isoagglutinins in IVIG by two to three titer steps compared with lots produced without IAC. The median anti-A and anti-B titers with IAC were 1:8 and 1:4, respectively, when measured by the Ph. Eur. direct method, and 1:2 and <1, respectively, when measured by the Ph. Eur. indirect method. The isoagglutinin flow cytometry assay showed an 87-90 % reduction in isoagglutinins in post-IAC versus pre-IAC fractions. IAC alone reduced anti-A and anti-B of the IgMs isotype by 92.5-97.8 % and 95.4-99.2 %, respectively. Other product quality characteristics were similar with and without IAC. CONCLUSIONS IAC is an effective method for reducing isoagglutinin levels in IVIG, and it is feasible on an industrial scale.
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33
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Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, El-Gamal Y, Harville TO, Hossny E, Mazer B, Nelson R, Secord E, Jordan SC, Stiehm ER, Vo AA, Ballow M. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol 2016; 139:S1-S46. [PMID: 28041678 DOI: 10.1016/j.jaci.2016.09.023] [Citation(s) in RCA: 407] [Impact Index Per Article: 45.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 09/12/2016] [Accepted: 09/23/2016] [Indexed: 12/20/2022]
Abstract
Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence-based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.
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Affiliation(s)
- Elena E Perez
- Allergy Associates of the Palm Beaches, North Palm Beach, Fla.
| | - Jordan S Orange
- Department of Pediatrics, Section of Immunology Allergy and Rheumatology, Center for Human Immunobiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Tex
| | - Francisco Bonilla
- Department of Pediatrics, Clinical Immunology Program, Children's Hospital Boston and Harvard Medical School, Boston, Mass
| | - Javier Chinen
- Department of Pediatrics, Section of Immunology Allergy and Rheumatology, Center for Human Immunobiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Tex
| | - Ivan K Chinn
- Department of Pediatrics, Section of Immunology Allergy and Rheumatology, Center for Human Immunobiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Tex
| | - Morna Dorsey
- Department of Pediatrics, Allergy, Immunology and BMT Division, Benioff Children's Hospital and University of California, San Francisco, Calif
| | - Yehia El-Gamal
- Department of Pediatrics, Pediatric Allergy and Immunology Unit, Children's Hospital and Ain Shams University, Cairo, Egypt
| | - Terry O Harville
- Departments of Pathology and Laboratory Services and Pediatrics, University of Arkansas, Little Rock, Ark
| | - Elham Hossny
- Department of Pediatrics, Pediatric Allergy and Immunology Unit, Children's Hospital and Ain Shams University, Cairo, Egypt
| | - Bruce Mazer
- Department of Pediatrics, Allergy and Immunology, Montreal Children's Hospital and McGill University, Montreal, Quebec, Canada
| | - Robert Nelson
- Department of Medicine and Pediatrics, Division of Hematology and Oncology and Stem Cell Transplantation, Riley Hospital, Indiana University School of Medicine and the IU Melvin and Bren Simon Cancer Center, Indianapolis, Ind
| | - Elizabeth Secord
- Department of Pediatrics, Wayne State University, Children's Hospital of Michigan, Detroit, Mich
| | - Stanley C Jordan
- Nephrology & Transplant Immunology, Kidney Transplant Program, David Geffen School of Medicine at UCLA and Cedars-Sinai Medical Center, Los Angeles, Calif
| | - E Richard Stiehm
- Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, Calif
| | - Ashley A Vo
- Transplant Immunotherapy Program, Comprehensive Transplant Center, Kidney Transplant Program, Cedars-Sinai Medical Center, Los Angeles, Calif
| | - Mark Ballow
- Department of Pediatrics, Division of Allergy & Immunology, University of South Florida, Morsani College of Medicine, Johns Hopkins All Children's Hospital, St Petersburg, Fla
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34
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Moon JW, Lee SH, Oh YK, Choi DY, Yu ST. Autoimmune Hemolytic Anemia after Intravenous Immunoglobulin Therapy in a Child with Kawasaki Disease. CLINICAL PEDIATRIC HEMATOLOGY-ONCOLOGY 2016. [DOI: 10.15264/cpho.2016.23.2.162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Joung Whan Moon
- Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
| | - Seung Hyun Lee
- Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
| | - Yeon Kyun Oh
- Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
| | - Du Young Choi
- Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
| | - Seung Taek Yu
- Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea
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35
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Lakkaraja M, Jin JC, Manotas KC, Vinograd CA, Ferd P, Gabor J, Wissert M, Berkowitz RL, McFarland JG, Bussel JB. Blood group A mothers are more likely to develop anemia during antenatal intravenous immunoglobulin treatment of fetal and neonatal alloimmune thrombocytopenia. Transfusion 2016; 56:2449-2454. [PMID: 27611703 DOI: 10.1111/trf.13779] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 04/28/2016] [Accepted: 05/26/2016] [Indexed: 11/30/2022]
Abstract
BACKGROUND Incompatibility between parental platelet (PLT) antigens may lead to sensitization of mother and development of fetal and neonatal alloimmune thrombocytopenia (FNAIT) resulting in fetal thrombocytopenia. Intravenous immunoglobulin (IVIG) with or without prednisone is the most effective, evidence-based antenatal treatment for subsequent FNAIT-affected pregnancies. IVIG infusion causes hemolysis in other settings, the degree depending upon patient blood groups (BGs). STUDY DESIGN AND METHODS In ClinicalTrials.gov NCT00194987, 102 pregnant women received randomized antenatal treatment: Arm A received 2 g/kg/week IVIG; Arm B received 1 g/kg/week IVIG + 0.5 mg/kg/day prednisone. This post hoc analysis explored BG and anemia in 69 FNAIT mothers treated with Arm A or Arm B without salvage treatment to explore the effects of IVIG and steroid treatment on development of anemia in these women. Mothers whose treatment changed, for example, those with insufficient or unknown fetal PLT response who received salvage therapy, were excluded. RESULTS For Arm A, 17 of 21 (hemoglobin [Hb] < 10 g/dL) mothers with anemia but only three of 15 mothers without anemia had BG-A and/or BG-B (p = 0.0005). BG was unrelated to anemia in Arm B; only nine of 33 Arm B mothers became anemic during treatment. The mean decrease in Hb level in women with BG-non-O was 1.9 g/dL and in women with BG-O was 1.1 g/dL (p = 0.004). Anemia was not caused by iron deficiency; the lowest mean corpuscular volume was 79. CONCLUSION FNAIT women with BG-non-O more frequently develop anemia secondary to high-dose IVIG infusion (2 g/kg/week), quite possibly from isohemagglutinin-mediated hemolysis; maternal Hb requires monitoring. IVIG at 1 g/kg/week did not cause anemia in women with BG-non-O; concomitant prednisone likely alleviated the IVIG effect. Maternal BG could influence selection of antenatal treatment for FNAIT.
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Affiliation(s)
- Madhavi Lakkaraja
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Jenny C Jin
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Karen C Manotas
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Cheryl A Vinograd
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Polina Ferd
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Julia Gabor
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Megan Wissert
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University
| | - Richard L Berkowitz
- Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, New York
| | - Janice G McFarland
- Platelet and Neutrophil Immunology Laboratory, Blood Center of Wisconsin, Milwaukee, Wisconsin.,Department of Medicine, Division of Hematology-Oncology, Medical College of Wisconsin, Wauwatosa, Wisconsin
| | - James B Bussel
- Department of Pediatrics, Division of Hematology, Weill Medical College of Cornell University.
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36
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Staley EM, Carruba SS, Manning M, Pham HP, Williams LA, Marques MB, Locke JE, Lorenz RG. Anti-Blood Group Antibodies in Intravenous Immunoglobulin May Complicate Interpretation of Antibody Titers in ABO-Incompatible Transplantation. Am J Transplant 2016; 16:2483-6. [PMID: 26913485 DOI: 10.1111/ajt.13760] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 02/09/2016] [Accepted: 02/14/2016] [Indexed: 01/25/2023]
Abstract
Patients receiving ABO-incompatible (ABOi) kidney transplants are treated before and after transplant with combination therapy, such as intravenous immunoglobulin (IVIG) and therapeutic plasma exchange, to prevent allograft rejection by reducing anti-A and anti-B titers. Although generally considered safe, it is well known that commercial IVIG products contain detectable anti-A and anti-B, which can be associated with hemolysis. Different preparative manufacturing techniques during the production of IVIG affect ABO antibody levels in IVIG preparations; therefore, some manufacturers now use new methods to reduce anti-A/B levels at the preproduction stage. The variations in implementing these strategies creates the potential for significant variation in antibody titers between products and, in some cases, even between lots of the same IVIG product. We report a case of persistently elevated anti-A titers in an ABOi kidney transplant recipient associated with elevated ABO antibody titers present in the preparation of IVIG used at our facility.
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Affiliation(s)
- E M Staley
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
| | - S S Carruba
- Pharmacy Department, University of Alabama at Birmingham, Birmingham, AL
| | - M Manning
- Pharmacy Department, University of Alabama at Birmingham, Birmingham, AL
| | - H P Pham
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
| | - L A Williams
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
| | - M B Marques
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
| | - J E Locke
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - R G Lorenz
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
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37
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Markvardsen LH, Christiansen I, Jakobsen J. Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. Transfusion 2016; 56:2443-2448. [DOI: 10.1111/trf.13727] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 06/01/2016] [Accepted: 06/05/2016] [Indexed: 12/11/2022]
Affiliation(s)
| | - Ingelise Christiansen
- Department of Neurology; Rigshospitalet, Copenhagen University Hospital; Copenhagen Denmark
| | - Johannes Jakobsen
- Department of Neurology; Rigshospitalet, Copenhagen University Hospital; Copenhagen Denmark
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38
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Telcharova-Mihaylovska A, Stefanov S, Nikolova I. Kawasaki disease and acute haemolytic anaemia after two IVIG infusions. BIOTECHNOL BIOTEC EQ 2016. [DOI: 10.1080/13102818.2016.1159529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Affiliation(s)
- Albena Telcharova-Mihaylovska
- Clinic of Rheumatology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
| | - Stefan Stefanov
- Clinic of Rheumatology, Pediatric University Hospital SBALDB “Prof. Ivan Mitev”, Medical University of Sofia, Sofia, Bulgaria
| | - Irina Nikolova
- Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
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39
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Pulvirenti F, Granata G, Girelli G, Quinti I. Immunoglobulin-induced hemolysis, splenomegaly and inflammation in patients with antibody deficiencies. Expert Rev Clin Immunol 2016; 12:725-31. [PMID: 26854522 DOI: 10.1586/1744666x.2016.1151787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
IgG replacement for primary antibody deficiencies is a safe treatment administered to prevent recurrent infections and reduce mortality. Recently, several reports described acute hemolytic episodes following IgG administration due to a passive transfer of blood group alloantibodies, including anti-A, anti-B, as well as anti-Rh antibodies. Here, we reviewed and discussed the consequences of passively transferred RBCs antibodies. The chronic passive transfer of alloantibodies might also cause a subclinical condition due to a compensated extravascular chronic hemolysis with poorly understood consequences. This phenomenon might possibly represent an unrecognized cause of splenomegaly and might contribute to inflammation in patients with primary antibody deficiencies.
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Affiliation(s)
- Federica Pulvirenti
- a Centre for Primary Immune Deficiencies, Department of Molecular Medicine , Sapienza University of Rome , Rome , Italy
| | - Guido Granata
- a Centre for Primary Immune Deficiencies, Department of Molecular Medicine , Sapienza University of Rome , Rome , Italy
| | - Gabriella Girelli
- b Unit of Immunohematology and Transfusion Medicine , Sapienza University of Rome , Rome , Italy
| | - Isabella Quinti
- a Centre for Primary Immune Deficiencies, Department of Molecular Medicine , Sapienza University of Rome , Rome , Italy
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40
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Živković S. Intravenous immunoglobulin in the treatment of neurologic disorders. Acta Neurol Scand 2016; 133:84-96. [PMID: 25997034 DOI: 10.1111/ane.12444] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2015] [Indexed: 12/17/2022]
Abstract
Intravenous immunoglobulins (IVIGs) are often used in the treatment of autoimmune disorders and immunodeficiencies, and it has been estimated that neurologic indications can account for up to 43% of IVIG used in clinical practice. In neurologic clinical practice, IVIG is used for acute therapy of newly diagnosed autoimmune disorders or exacerbations of pre-existing conditions, or as long-term maintenance treatment for chronic disorders. IVIG exerts its effects on humoral and cell-based immunity through multiple pathways, without a single dominant mechanism. Clinical use of IVIG has been supported by guidelines from American Academy of Neurology and European Federation of Neurologic Societies. IVIG is generally recommended for the treatment of Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy in adults, multifocal motor neuropathy and myasthenia gravis, and should be considered as a treatment option for dermatomyositis in adults and Lambert-Eaton myasthenic syndrome. Additional potential indications include stiff person syndrome, multiple sclerosis during pregnancy or while breastfeeding, refractory autoimmune epilepsy, and paraneoplastic disorders. Clinical use of IVIG is mostly safe but few adverse effects may still occur with potentially severe complications, including aseptic meningitis and thromboembolism. In addition to intravenous route (IVIG), subcutaneous immunoglobulins have been used as an alternative treatment option, especially in patients with limited intravenous access. Treatment with IVIG is effective in various autoimmune diseases, but its broader use is constrained by limited supply. This review evaluates the use of immunoglobulins in treatment of neurologic diseases.
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Affiliation(s)
- S. Živković
- Department of Neurology; University of Pittsburgh Medical Center; Pittsburgh PA USA
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41
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Jovanovich E, Karam C. Human immune globulin infusion in the management of multifocal motor neuropathy. Degener Neurol Neuromuscul Dis 2015; 6:1-12. [PMID: 30050363 PMCID: PMC6053084 DOI: 10.2147/dnnd.s96258] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Multifocal motor neuropathy (MMN) is a debilitating and rare disease causing profound weakness with minimal to no sensory symptoms. Conduction block is frequently seen on electrodiagnostic testing. An immune-mediated pathology is suspected though the exact underlying pathophysiology has yet to be elucidated. The presence of anti-GM1 ganglioside IgM antibodies coupled with favorable response to intravenous and subcutaneous immunoglobulins supports a complement-mediated mechanism which leads to destruction of nerve tissue with probable predilection to the nodes of Ranvier. High-dose immunoglobulin currently is the only treatment with proven efficacy for MMN patients. Unfortunately, many patients experience decreased responsiveness to immunoglobulins over time, requiring higher and more frequent dosing. In this review, we will focus on the pharmacology, efficacy, safety, and tolerability of intravenous and subcutaneous immune globulin infusion for treatment of MMN.
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Affiliation(s)
| | - Chafic Karam
- Department of Neurology, The University of North Carolina, Chapel Hill, NC, USA,
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42
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Bamoulid J, Staeck O, Halleck F, Dürr M, Paliege A, Lachmann N, Brakemeier S, Liefeldt L, Budde K. Advances in pharmacotherapy to treat kidney transplant rejection. Expert Opin Pharmacother 2015; 16:1627-48. [PMID: 26159444 DOI: 10.1517/14656566.2015.1056734] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Current immunosuppressive combination therapy provides excellent prevention of T-cell-mediated rejection following renal transplantation; however, antibody-mediated rejection remains of high concern and accounts for a large number of long-term allograft losses. The recent development of protocol biopsies resulted in the definition of subclinical rejection (SCR), showing histologic evidence for rejection but unremarkable clinical course. AREAS COVERED This review describes the current knowledge and evidence of pharmacotherapy to treat kidney allograft rejections and covers SCR treatment options. Each substance is analyzed with regard to its classical indication and further discussed for the treatment of other forms of rejection. EXPERT OPINION Despite a lack of randomized trials, early acute T-cell-mediated rejection can be treated effectively in most cases without graft loss. The necessity to treat SCR is currently unclear. Due to a lack of effective therapies, new treatment approaches for antibody-mediated rejection are an urgent medical need to improve long-term outcomes. Future research should aim to better define pathophysiology and histology, stratify risk, and develop rational treatment strategies from randomized controlled trials, in order to establish the value of novel therapies in the arsenal of rejection pharmacotherapy. However, the effective prevention of rejection with minimal side effects still remains the goal in immunosuppression.
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Affiliation(s)
- Jamal Bamoulid
- Charité Universitätsmedizin Berlin, Department of Nephrology , Berlin , Germany +49 30 450 514002 ; +49 30 450 514902 ;
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Salvatore A, Esin S, Batoni G, Ascione E, Farina C, Nardini C. Anti-A and anti-B hemagglutinin depletion during Cohn purification process of 5% immunoglobulin. Transfusion 2015; 55 Suppl 2:S110-6. [PMID: 26174888 DOI: 10.1111/trf.13112] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Polyvalent immunoglobulin G (IgG) products obtained by fractionation of human plasma are widely used to treat a broad range of conditions, including immunodeficiency syndromes and autoimmune, inflammatory, and infectious diseases. For high-quality products and to minimize adverse events related to the use of intravenous IgG (IVIG) it is very important to perform detailed analyses of their components. One of these components, that in rare cases can cause severe hemolytic conditions, is the amount of hemagglutinins, natural antibodies that bind A and/or B (anti-A or -B) antigens present in red blood cells (RBCs). STUDY DESIGN AND METHODS To characterize different IgG batches and to monitor the efficacy of the production procedure in the hemagglutinin reduction, a direct agglutination test (DAT) and a new flow cytometry (FC)-based assay were used for measuring the activity and the content of hemagglutinins in IgG samples obtained at different stages of the purification process. RESULTS A total of 113 batches of 5% IVIG, produced in 2013 by Kedrion Biopharma, were analyzed for the ability to agglutinate RBCs by DAT. All batches tested were within the limits set by the European Pharmacopoeia. Three batches of 5% IVIG were analyzed for their hemagglutinin levels. The finished products and the production intermediates were evaluated by the DAT and the FC assay. A significant decrease of anti-A and anti-B titer after the Fraction (F)III precipitation was observed in all batches tested and an evaluation of the results obtained by the two methods was performed. CONCLUSIONS This study shows that the hemagglutinin titer, accurately measured in a high number of 5% IVIG batches, is within the allowed limits for the DAT method. The specific production process employed, in particular the FIII precipitation step, successfully removes IgM and significantly reduces IgG class hemagglutinins.
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Affiliation(s)
| | - Semih Esin
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giovanna Batoni
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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Winiecki S, Baer B, Chege W, Jankosky C, Mintz P, Baker M, Woodworth T, Nguyen M. Complementary use of passive surveillance and Mini-Sentinel to better characterize hemolysis after immune globulin. Transfusion 2015; 55 Suppl 2:S28-35. [PMID: 26174895 DOI: 10.1111/trf.13116] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Hemolysis after intravenous immune globulins (IGIVs) is a known complication, but expanding indications and recent manufacturing changes warrant ongoing postmarketing surveillance. Characterization of post-IGIV hemolysis to date has been limited to small case series. STUDY DESIGN AND METHODS We queried the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) from 2007 to 2014. All reported post-IGIV hemolysis cases were classified using a prespecified case definition and a case series analysis performed. We also conducted two assessments using FDA's Mini-Sentinel (MS) system to quantify the risk of hemolysis by six product indications and by IGIV formulation and evaluate the onset interval. RESULTS A total of 109 FAERS cases met our definition. For cases with available information, 83% (66/80) received IGIV doses of at least 2 g/kg, 98.1% (51/52) had non-O blood group, and 75% (64/85) of events occurred within 4 days of IGIV exposure. We identified 313,045 treatment episodes and 337 post-IGIV hemolytic events in MS from 2006 to 2014, with 72% occurring within 2 days. Rates of hemolysis were highest among patients with Kawasaki disease (KD) and immune thrombocytopenia (ITP). The risk among patients receiving nonlyophilized products was 2.3 times higher than that in patients receiving lyophilized products. CONCLUSION With the largest case series to date, FAERS data support that higher doses and non-O blood group are key risk factors. The incident rate of post-IGIV hemolysis is estimated at one per 1000 IGIV treatment episodes, with most occurring within 2 days of exposure. The risk is higher in patients with KD and ITP and after receipt of nonlyophilized IGIV.
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Affiliation(s)
- Scott Winiecki
- Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
| | - Bethany Baer
- Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
| | - Wambui Chege
- Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
| | - Christopher Jankosky
- Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
| | - Paul Mintz
- Division of Hematology Clinical Review, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
| | - Meghan Baker
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.,Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Tiffany Woodworth
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
| | - Michael Nguyen
- Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland
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Flegel WA. Pathogenesis and mechanisms of antibody-mediated hemolysis. Transfusion 2015; 55 Suppl 2:S47-58. [PMID: 26174897 DOI: 10.1111/trf.13147] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 03/24/2015] [Accepted: 03/25/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND The clinical consequences of antibodies to red blood cells (RBCs) have been studied for a century. Most clinically relevant antibodies can be detected by sensitive in vitro assays. Several mechanisms of antibody-mediated hemolysis are well understood. Such hemolysis after transfusion is reliably avoided in a donor-recipient pair, if one individual is negative for the cognate antigen to which the other has the antibody. STUDY DESIGN AND RESULTS Mechanisms of antibody-mediated hemolysis were reviewed based on a presentation at the Strategies to Address Hemolytic Complications of Immune Globulin Infusions Workshop addressing intravenous immunoglobulin (IVIG) and ABO antibodies. The presented topics included the rates of intravascular and extravascular hemolysis; immunoglobulin (Ig)M and IgG isoagglutinins; auto- and alloantibodies; antibody specificity; A, B, A,B, and A1 antigens; A1 versus A2 phenotypes; monocytes-macrophages, other immune cells, and complement; monocyte monolayer assay; antibody-dependent cell-mediated cytotoxicity; and transfusion reactions due to ABO and other antibodies. CONCLUSION Several clinically relevant questions remained unresolved, and diagnostic tools were lacking to routinely and reliably predict the clinical consequences of RBC antibodies. Most hemolytic transfusion reactions associated with IVIG were due to ABO antibodies. Reducing the titers of such antibodies in IVIG may lower the frequency of this kind of adverse event. The only way to stop these events is to have no anti-A or anti-B in the IVIG products.
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Affiliation(s)
- Willy A Flegel
- Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland
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Pendergrast J, Willie-Ramharack K, Sampson L, Laroche V, Branch DR. The role of inflammation in intravenous immune globulin-mediated hemolysis. Transfusion 2015; 55 Suppl 2:S65-73. [PMID: 26174900 DOI: 10.1111/trf.13097] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Intravenous immune globulin (IVIG) therapy has shown great success in a number of autoimmune and inflammatory conditions and its use continues to increase worldwide. There is growing awareness of significant side effects of high-dose IVIG: however, particularly severe hemolysis in patients that are non-group O. It has been proposed that IVIG-associated hemolysis may be heralded by an existing inflammatory condition. In the work presented herein, we have provided a review of the pathophysiology of inflammation, particularly as it applies in immune-mediated red blood cell hemolysis, and a summary of previous publications that suggest an association between IVIG-mediated hemolysis and a state of existing inflammation. In addition, preliminary results from a prospective study to address the mechanism of IVIG-associated hemolysis are provided. These preliminary data support the idea of an existing inflammatory condition preceding overt hemolysis after high-dose IVIG therapy that: 1) is restricted to non-group O patients, 2) is seen when using IVIG doses of more than 2 g/kg, 3) involves an activated mononuclear phagocyte system, 4) may be presaged by a significant increase in the anti-inflammatory cytokine interleukin-1 receptor agonist, and 5) is independent of secretor status.
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Affiliation(s)
- Jacob Pendergrast
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
| | | | - Lorna Sampson
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
| | - Vincent Laroche
- Institut Universitaire de Cardiologie et Pneumologie de Québec & CHU de Québec and Hôpitaux Enfant-Jésus et Saint-Sacrement, Quebec City, Quebec, Canada
| | - Donald R Branch
- Centre for Innovation, Canadian Blood Services, Toronto, Ontario, Canada
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Management of adverse events in the treatment of patients with immunoglobulin therapy: A review of evidence. Autoimmun Rev 2015; 15:71-81. [PMID: 26384525 DOI: 10.1016/j.autrev.2015.09.002] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 09/08/2015] [Indexed: 12/12/2022]
Abstract
Immunoglobulin (IG) therapy is actually used for a broad range of diseases including primary and secondary immunodeficiency disorders, and autoimmune diseases. This therapy is available for intravenous (IV) and subcutaneous (SC) administration. The efficacy of the IG therapy has been demonstrated in numerous studies and across different diseases. Generally, IG infusions are well tolerated; however some well-known adverse reactions, ranging from mild to severe, are associated with the therapy. The most common adverse reactions including headache, nausea, myalgia, fever, chills, chest discomfort, skin and anaphylactic reactions, could arise immediately during or after the infusion. Delayed events could be more severe and include migraine headaches, aseptic meningitis, haemolysis renal impairment and thrombotic events. This paper reviews all the potential adverse events related to IG therapy and establishes a comprehensive guideline for the management of these events. Moreover it resumes the opinions and clinical experience of expert endorsers on the utilization of the treatment. Published data were classified into levels of evidence and the strength of the recommendation was given for each intervention according to the GRADE system.
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Lasica M, Zantomio D. Severe intravenous immunoglobulin-induced hemolysis with pigment nephropathy managed with red cell exchange. J Clin Apher 2015; 31:464-6. [PMID: 26297048 DOI: 10.1002/jca.21416] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 06/29/2015] [Accepted: 06/30/2015] [Indexed: 11/10/2022]
Abstract
We report on the use of red cell exchange in a case of severe intravenous immune globulin induced hemolysis and pigment nephropathy. Renal impairment and hemoglobinuria were not ameliorated by supportive measures including hydration. Partial red cell exchange with group O blood reduced hemoglobinuria and appeared to stabilize renal function. This is the first report on the use of red cell exchange in this clinical setting. J. Clin. Apheresis 31:464-466, 2016. © 2015 Wiley Periodicals, Inc.
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Affiliation(s)
- Masa Lasica
- Clinical Haematology Department, Austin Health, Victoria, Australia
| | - Daniela Zantomio
- Clinical Haematology Department, Austin Health, Victoria, Australia.
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Siani B, Willimann K, Wymann S, Marques Antunes A, Widmer E. Donor screening reduces the isoagglutinin titer in immunoglobulin products. Transfusion 2015; 55 Suppl 2:S95-7. [DOI: 10.1111/trf.13095] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
| | | | - Sandra Wymann
- Product Development; CSL Behring AG; Berne Switzerland
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