Did you mean: alloimmunization
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Blood Jun 2023Neonatal thrombocytopenia, defined as the presence of a circulating platelet count <150 × 109/L, is a common abnormality in babies admitted to neonatal intensive care... (Review)
Review
Neonatal thrombocytopenia, defined as the presence of a circulating platelet count <150 × 109/L, is a common abnormality in babies admitted to neonatal intensive care units. Thrombocytopenia that is typically mild and self-limiting often accompanies neonatal stress in scenarios such as premature delivery or intrauterine growth restriction. However, the differential diagnosis of neonatal thrombocytopenia is wide and includes potentially life-threatening disorders, such as bacterial sepsis, viral infection, and necrotizing enterocolitis. Distinguishing these causes of thrombocytopenia from entities such as genetic thrombocytopenia and fetal and neonatal alloimmune thrombocytopenia is critical for the accurate quantitation of significant adverse events, such as intracranial bleeding, and for the selection of treatments, such as platelet transfusion. In this review, we focus on common differential diagnoses of neonatal thrombocytopenia and highlight how the landscape of diagnosis and management is changing with recent advances in genomic technology and the completion of pivotal clinical trials of platelet transfusion practice. Increasing evidence highlights the need for judicious and restrictive use of platelet transfusions in neonates.
Topics: Humans; Infant, Newborn; Intracranial Hemorrhages; Platelet Count; Platelet Transfusion; Prenatal Care; Thrombocytopenia, Neonatal Alloimmune
PubMed: 36787503
DOI: 10.1182/blood.2022018017 -
Archivos Argentinos de Pediatria Jun 2021Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm... (Review)
Review
Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.
Topics: Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Placenta; Platelet Count; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34033425
DOI: 10.5546/aap.2021.eng.e202 -
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 -
American Journal of Obstetrics and... Aug 2021Fetal and neonatal alloimmune thrombocytopenia, the platelet equivalent of hemolytic disease of the fetus and newborn, can have devastating effects on both the fetus and... (Review)
Review
Fetal and neonatal alloimmune thrombocytopenia, the platelet equivalent of hemolytic disease of the fetus and newborn, can have devastating effects on both the fetus and neonate. Current management of fetal and neonatal alloimmune thrombocytopenia in a subsequent affected pregnancy involves antenatal administration of intravenous immune globulin and prednisone to the pregnant woman to prevent the development of severe fetal thrombocytopenia and secondary intracranial hemorrhage in utero. That therapy has proven to be highly effective but is associated with maternal side effects and is expensive. This commentary describes 4 advances that could substantially change the current approach to detecting and managing fetal and neonatal alloimmune thrombocytopenia in the near future. The first would be an introduction of a program to screen all antepartum patients in this country for pregnancies at risk of developing fetal and neonatal alloimmune thrombocytopenia. Strategies to implement this complex process have been described. A second advance is testing of cell-free fetal DNA obtained from maternal blood to noninvasively determine the fetal human platelet antigen 1 genotype. A third, in preliminary development, is creation of a prophylactic product that would be the platelet equivalent of Rh immune globulin (RhoGAM). Finally, a fourth major potential advance is the development of neonatal Fc receptor inhibitors to replace the current medical therapy administered to pregnant women with an affected fetus. Neonatal Fc receptor recycles plasma immunoglobulin G to increase its half-life and is the means by which immunoglobulin G crosses the placenta from the maternal to the fetal circulation. Blocking the neonatal Fc receptor is an ideal way to prevent maternal immunoglobulin G antibody from causing fetal and neonatal alloimmune thrombocytopenia in a fetus at risk of developing that disorder. The pertinent pathophysiology and rationale for each of these developments will be presented in addition to our thoughts relating to steps that must be taken and difficulties that each approach would face for them to be successfully implemented.
Topics: Antigens, Human Platelet; Cell-Free Nucleic Acids; Drug Development; Female; Genotype; Glucocorticoids; Histocompatibility Antigens Class I; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunologic Factors; Integrin beta3; Maternal-Fetal Exchange; Noninvasive Prenatal Testing; Prednisone; Pregnancy; Prenatal Diagnosis; Receptors, Fc; Risk Assessment; Thrombocytopenia, Neonatal Alloimmune
PubMed: 33839095
DOI: 10.1016/j.ajog.2021.04.211 -
Blood Nov 2021
Topics: CD36 Antigens; Humans; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34735001
DOI: 10.1182/blood.2021012454 -
NeoReviews Jul 2022Immune-mediated thrombocytopenia in neonates is caused by the transplacental passage of maternally derived antiplatelet antibodies. The 2 most common causes include... (Review)
Review
Immune-mediated thrombocytopenia in neonates is caused by the transplacental passage of maternally derived antiplatelet antibodies. The 2 most common causes include neonatal alloimmune thrombocytopenia, which leads to significant thrombocytopenia and risk of intracranial hemorrhage, and autoimmune thrombocytopenia, which is generally less severe. No specific guidelines for prenatal management exist for either disease; however, intravenous immune globulin treatments and systemic steroids for women with at-risk pregnancies can be useful in both diseases. In this review, we discuss the current literature and management strategies for both pregnant women and newborns with immune-mediated thrombocytopenia.
Topics: Female; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 35773506
DOI: 10.1542/neo.23-7-e462 -
Experimental Eye Research May 2022Despite constant exposure to various environmental stimuli, the ocular surface remains intact and uninflamed while maintaining the transparency of the cornea and its... (Review)
Review
Despite constant exposure to various environmental stimuli, the ocular surface remains intact and uninflamed while maintaining the transparency of the cornea and its visual function. This 'immune privilege' of the ocular surface is not simply a result of the physical barrier function of the mucosal lining but, more importantly, is actively maintained through a variety of immunoregulatory mechanisms that prevent the disruption of immune homeostasis. In this review, we focus on essential molecular and cellular players that promote immune quiescence in steady-state conditions and suppress inflammation in disease-states. Specifically, we examine the interactions between the ocular surface and its local draining lymphoid compartment, by encompassing the corneal epithelium, corneal nerves and cornea-resident myeloid cells, conjunctival goblet cells, and regulatory T cells (Treg) in the context of ocular surface autoimmune inflammation (dry eye disease) and alloimmunity (corneal transplantation). A better understanding of the immunoregulatory mechanisms will facilitate the development of novel, targeted immunomodulatory strategies for a broad range of ocular surface inflammatory disorders.
Topics: Conjunctiva; Cornea; Corneal Transplantation; Dry Eye Syndromes; Humans; Inflammation
PubMed: 35257715
DOI: 10.1016/j.exer.2022.109007 -
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