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Blood Apr 2019Blood transfusion is the most common procedure completed during a given hospitalization in the United States. Although often life-saving, transfusions are not risk-free.... (Review)
Review
Blood transfusion is the most common procedure completed during a given hospitalization in the United States. Although often life-saving, transfusions are not risk-free. One sequela that occurs in a subset of red blood cell (RBC) transfusion recipients is the development of alloantibodies. It is estimated that only 30% of induced RBC alloantibodies are detected, given alloantibody induction and evanescence patterns, missed opportunities for alloantibody detection, and record fragmentation. Alloantibodies may be clinically significant in future transfusion scenarios, potentially resulting in acute or delayed hemolytic transfusion reactions or in difficulty locating compatible RBC units for future transfusion. Alloantibodies can also be clinically significant in future pregnancies, potentially resulting in hemolytic disease of the fetus and newborn. A better understanding of factors that impact RBC alloantibody formation may allow general or targeted preventative strategies to be developed. Animal and human studies suggest that blood donor, blood product, and transfusion recipient variables potentially influence which transfusion recipients will become alloimmunized, with genetic as well as innate/adaptive immune factors also playing a role. At present, judicious transfusion of RBCs is the primary strategy invoked in alloimmunization prevention. Other mitigation strategies include matching RBC antigens of blood donors to those of transfusion recipients or providing immunomodulatory therapies prior to blood product exposure in select recipients with a history of life-threatening alloimmunization. Multidisciplinary collaborations between providers with expertise in transfusion medicine, hematology, oncology, transplantation, obstetrics, and immunology, among other areas, are needed to better understand RBC alloimmunization and refine preventative strategies.
Topics: ABO Blood-Group System; Blood Group Incompatibility; Erythrocyte Transfusion; Erythrocytes; Humans; Isoantibodies; Transfusion Reaction
PubMed: 30808636
DOI: 10.1182/blood-2018-08-833962 -
Advances in Neonatal Care : Official... Apr 2021Neonatal alloimmune thrombocytopenia (NAIT) is defined as an uncommon platelet disorder caused by maternal alloimmunization to human-specific antigens (HPAs) that are... (Review)
Review
BACKGROUND
Neonatal alloimmune thrombocytopenia (NAIT) is defined as an uncommon platelet disorder caused by maternal alloimmunization to human-specific antigens (HPAs) that are paternally inherited, resulting in low fetal/neonatal platelet levels and debilitating effects on the newborn. The incidence of NAIT is 1 in every 1000 live births within the United States; it is the most common cause of severe thrombocytopenia (<30 × 109/L) and intracranial hemorrhage in term newborns.
PURPOSE
The purpose of this article is to discuss the pathophysiology, clinical manifestations, diagnosis, and treatment of NAIT and its implications upon the lifespan of the neonate.
METHODS
A literature review was conducted using PubMed, CINAHL, and Google Scholar (2014-2019). Search terms included NAIT, neonatal/fetal alloimmune thrombocytopenia, newborn platelets, and intracranial bleeding and NAIT.
RESULTS
NAIT can affect first pregnancies and often goes undiagnosed until delivery. Universal screening tools with a focus on HPA-1a typing via noninvasive testing have been successfully trialed and have yielded promising results indicating a 75% reduction in risks associated with NAIT; however, none have been incorporated into practice and prophylactic treatment remains unavailable.
IMPLICATIONS FOR RESEARCH
Adopting a universal screening tool and prophylaxis for NAIT would allow for early diagnosis and treatment in utero.
IMPLICATIONS FOR PRACTICE
Many healthcare providers are not familiar with NAIT often focusing on other causes of thrombocytopenia as a potential diagnosis.
Topics: Antigens, Human Platelet; Blood Platelets; Female; Fetus; Humans; Infant, Newborn; Pregnancy; Prenatal Care; Thrombocytopenia, Neonatal Alloimmune
PubMed: 32657948
DOI: 10.1097/ANC.0000000000000775 -
Vox Sanguinis Aug 2015Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal... (Review)
Review
Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal anaemia with a risk for fetal death and to severe forms of neonatal hyperbilirubinaemia with a risk for kernicterus. Most severe cases are caused by anti-D, despite the introduction of antental and postnatal anti-D immunoglobulin prophylaxis. In general, red blood cell antibody screening programmes are aimed to detect maternal alloimmunization early in pregnancy to facilitate the identification of high-risk cases to timely start antenatal and postnatal treatment. In this review, an overview of the clinical relevance of red cell alloantibodies in relation to occurrence of HDFN and recent views on prevention, screening and treatment options of HDFN are provided.
Topics: Erythroblastosis, Fetal; Female; Humans; Immunotherapy; Infant, Newborn; Pregnancy; Rh-Hr Blood-Group System
PubMed: 25899660
DOI: 10.1111/vox.12265 -
Current Opinion in Organ Transplantation Aug 2020Despite significant improvement in pancreas allograft survival, rejection continues to be a major clinical problem. This review will focus on emerging literature related... (Review)
Review
PURPOSE OF REVIEW
Despite significant improvement in pancreas allograft survival, rejection continues to be a major clinical problem. This review will focus on emerging literature related to the impact of pretransplant and de-novo DSA (dnDSA) in pancreas transplant recipients, and the diagnosis and treatment of T-cell-medicated rejection (TCMR) and antibody-mediated rejection (ABMR) in this complex group of patients.
RECENT FINDINGS
Recent data suggest that pretransplant DSA and the emergence of dnDSA in pancreas transplant recipients are both associated with increased risk of ABMR. The pancreas allograft biopsy is essential for the specific diagnosis of TCMR and/or ABMR, distinguish rejection from other causes of graft dysfunction, and to guide-targeted therapy. This distinction is important especially in the setting of solitary pancreas transplants but also in simultaneous pancreas-kidney transplants where solid evidence has now emerged demonstrating discordant biopsy findings. Treatment of rejection in a functioning pancreas can prolong allograft survival.
SUMMARY
The accurate and timely diagnosis of active alloimmune destruction in pancreas transplant recipients is paramount to preserving graft function in the long term. This review will discuss new, rapidly evolving information that is valuable for the physician caring for these patients to achieve optimal immunological outcomes.
Topics: Allografts; Antibodies; Antibody Specificity; Graft Rejection; HLA Antigens; Histocompatibility; Humans; Pancreas Transplantation; Risk Factors; T-Lymphocytes; Transplantation Immunology; Transplantation, Homologous
PubMed: 32692039
DOI: 10.1097/MOT.0000000000000776 -
Transfusion Medicine and Hemotherapy :... Apr 2020Alloimmunization is caused by exposure to erythrocytes from a donor that expresses blood group antigens other than those of the recipient and is related to processes...
INTRODUCTION
Alloimmunization is caused by exposure to erythrocytes from a donor that expresses blood group antigens other than those of the recipient and is related to processes that alter the balance of the immune system. Knowing the pathophysiology of alloimmunization process is essential to understand clinical complications associated with this process.
PATIENTS AND METHODS
From October 2016 to April 2017, irregular antibody screening was performed in 1,434 polytransfused (compatible with the ABO and D system) patients by means of agglutination techniques using erythrocytes of a known phenotype of 44 patients with a positive alloantibody screening. Non-alloimmunized (control) subjects were matched for age, gender, pathology, and treatment group with alloimmunized patients. The subsets of B, T, and Treg lymphocytes were determined by flow cytometry.
RESULTS
The results of screening for alloantibodies in patients by specificity of antibodies were as follows: nonspecific (30%), followed by anti-Di (13%), anti-e (9%), anti-S (9%), anti-I (7%), anti-K (7%), and anti-P (7%). A lower percentage of CD4+ T lymphocytes and an increase of CD8+ T lymphocytes were observed in alloimmunized patients, as well as a low CD4/CD8 ratio (0.7 vs. 1.6, = 0.003), a higher percentage of B lymphocytes versus the control group (30 vs. 20%, = 0.003), and a decrease of Treg CD4+ lymphocytes versus the control group (3 vs. 12 cells/μL, = 0.043). These observations suggest that alloimmunized patients have important alterations in the number of some lymphocyte subsets that can be translated into clinical immune dysregulation.
CONCLUSION
A decreased CD4/CD8 ratio, increased B lymphocytes, and Treg lymphocyte deficiency are the most significant changes observed in alloimmunized patients.
PubMed: 32355475
DOI: 10.1159/000501861 -
Transfusion and Apheresis Science :... Oct 2020The components of the immune system may be present in early stages of embryonic and then fetal, then they reach maturity at different stages of pregnancy. Just as the... (Review)
Review
The components of the immune system may be present in early stages of embryonic and then fetal, then they reach maturity at different stages of pregnancy. Just as the growth and development of the components of the embryonic and then fetal immune system progressively mature, functions are acquired sequentially during the course of pregnancy, both the ability to mount a cell-mediated or antibody-mediated immune response and the tolerance towards a certain group of antigens. The fetus is immunocompetent because during this development, it acquires the ability to generate an immune response. As development takes place, the fetus also generates specific tolerance as it is exposed to genetically foreign and non-inherited maternal antigens. Nonetheless, the fetal immune system does not attack nor harm maternal tissues. At birth, the immune system, although developed, is not mature enough yet. Furthermore, passive transfer of maternal antibodies creates a unique scenario of compatibility that cannot be seen in children or adults. Recent advances in knowledge of fetal and neonatal immunology make it possible to recognize the risks associated with transfusion and how to resolve them.
Topics: Fetus; Humans; Immune Tolerance; Immunity; Infant, Newborn
PubMed: 32958398
DOI: 10.1016/j.transci.2020.102945 -
Transplantation Aug 2022Eosinophils are bone-marrow-derived granulocytes known for their ability to facilitate clearance of parasitic infections and their association with asthma and other... (Review)
Review
Eosinophils are bone-marrow-derived granulocytes known for their ability to facilitate clearance of parasitic infections and their association with asthma and other inflammatory diseases. The purpose of this review is to discuss the currently available human observational and animal experimental data linking eosinophils to the immunologic response in solid organ transplantation. First, we present observational human studies that demonstrate a link between transplantation and eosinophils yet were unable to define the exact role of this cell population. Next, we describe published experimental models and demonstrate a defined mechanistic role of eosinophils in downregulating the alloimmune response to murine lung transplants. The overall summary of this data suggests that further studies are needed to define the role of eosinophils in multiple solid organ allografts and points to the possibility of manipulating this cell population to improve graft survival.
Topics: Animals; Eosinophils; Graft Survival; Humans; Lung Transplantation; Mice; Organ Transplantation; Transplantation, Homologous
PubMed: 34966103
DOI: 10.1097/TP.0000000000004030 -
Transfusion Clinique Et Biologique :... Sep 2018Platelet transfusion in patients, particularly in onco-haematology, is frequent and can become chronic in some cases. Post-transfusion alloimmunization is often seen, in... (Review)
Review
Platelet transfusion in patients, particularly in onco-haematology, is frequent and can become chronic in some cases. Post-transfusion alloimmunization is often seen, in practice. The risk of this is significantly improved in multitransfused patients. Several classes of antigens binding on platelets (HLA and HPA) are involved and also red blood cell antigens (residual red blood cells in platelet concentrates). Platelet alloimmunization causes a poor transfusion response, refractoriness and, more rarely, post-transfusion purpura. In an alloimmunized recipient, the efficiency of platelet transfusion is based on the selection of compatible products. Significant technical progress means that several methods are currently available to ensure a good post-transfusion platelet count and a satisfactory clinical outcome for the patient.
Topics: Antibody Formation; Blood Platelets; Humans; Platelet Transfusion
PubMed: 29478960
DOI: 10.1016/j.tracli.2018.01.003 -
Prenatal Diagnosis Aug 2020Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of... (Review)
Review
Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.
Topics: Blood Transfusion, Intrauterine; Erythroblastosis, Fetal; Female; Fetal Diseases; History, 21st Century; Humans; Pregnancy; Prenatal Care; Prenatal Exposure Delayed Effects; Rh Isoimmunization
PubMed: 32108353
DOI: 10.1002/pd.5674 -
Transfusion Clinique Et Biologique :... Aug 2015Red blood cell (RBC) alloimmunization can be a life-threatening complication for patients with sickle cell disease (SCD) receiving therapeutic transfusions. Despite... (Review)
Review
Red blood cell (RBC) alloimmunization can be a life-threatening complication for patients with sickle cell disease (SCD) receiving therapeutic transfusions. Despite provision of extended antigen-matched donor RBCs, patients continue to develop antibodies due to high degree of polymorphisms in the immunogenic antigens in individuals of African ancestry. Identification of biomarkers of alloimmunization in this patient population is therefore of great interest and will help to identify in advance patients most likely to make antibodies in response to transfusion. We have recently identified altered T cell responses and innate immune abnormalities in alloimmunized SCD patients. In this paper, we summarize this work and propose our working model of how innate immune abnormalities can contribute to pathogenic T cell responses in alloimmunized SCD patients. We believe that unravelling the basis of such altered interactions at the cellular and molecular level will help future identification of biomarkers of alloimmunization with the goal that this information will ultimately help guide therapy in these patients.
Topics: Anemia, Sickle Cell; B-Lymphocytes; Biomarkers; Blood Group Incompatibility; Erythrocyte Transfusion; Erythrocytes; Heme; Heme Oxygenase-1; Hemin; Humans; Interleukin-10; Interleukin-12; Isoantibodies; Lymphocyte Cooperation; Membrane Proteins; Models, Immunological; Monocytes; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Transfusion Reaction
PubMed: 26056038
DOI: 10.1016/j.tracli.2015.05.005