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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 -
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 -
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 -
Blood Nov 2021
Topics: CD36 Antigens; Humans; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34735001
DOI: 10.1182/blood.2021012454 -
Transfusion Medicine and Hemotherapy :... Oct 2018Neonatal alloimmune neutropenia (NAIN, NAIN or NIN) is a neutrophil blood group antagonism, analogous to hemolytic disease of the fetus and newborn (HDFN) and... (Review)
Review
Neonatal alloimmune neutropenia (NAIN, NAIN or NIN) is a neutrophil blood group antagonism, analogous to hemolytic disease of the fetus and newborn (HDFN) and fetal/neonatal alloimmune thrombocytopenia (FNAIT). A limited number of prospective screening studies showed that granulocyte-specific antibodies were detectable in 0.35-1.1% of random postnatal maternal samples and that the incidence of NAIN was below 0.1%. Symptoms vary from none to mild skin infections, omphalitis or more severe infections like pneumonia, sepsis, and meningitis. Treatment of neonatal infection with antibiotics and granulocyte-colony stimulating factor is advised.
PubMed: 31049048
DOI: 10.1159/000492949 -
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 -
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 -
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 -
Frontiers in Immunology 2022The transcriptional regulation of B-cell response to antigen stimulation is complex and involves an intricate network of dynamic signals from cytokines and transcription... (Review)
Review
The transcriptional regulation of B-cell response to antigen stimulation is complex and involves an intricate network of dynamic signals from cytokines and transcription factors propagated from T-cell interaction. Long-term alloimmunity, in the setting of organ transplantation, is dependent on this B-cell response, which does not appear to be halted by current immunosuppressive regimens which are targeted at T cells. There is emerging evidence that shows that B cells have a diverse response to solid organ transplantation that extends beyond plasma cell antibody production. In this review, we discuss the mechanistic pathways of B-cell activation and differentiation as they relate to the transcriptional regulation of germinal center B cells, plasma cells, and memory B cells in the setting of solid organ transplantation.
Topics: B-Lymphocytes; Germinal Center; Graft Rejection; Histocompatibility; Organ Transplantation
PubMed: 36016958
DOI: 10.3389/fimmu.2022.895157 -
Hematology. American Society of... Dec 2016Blood group alloimmunization is "triggered" when a person lacking a particular antigen is exposed to this antigen during transfusion or pregnancy. Although exposure to... (Review)
Review
Blood group alloimmunization is "triggered" when a person lacking a particular antigen is exposed to this antigen during transfusion or pregnancy. Although exposure to an antigen is necessary for alloimmunization to occur, it is not alone sufficient. Blood group antigens are diverse in structure, function, and immunogenicity. In addition to red blood cells (RBCs), a recipient of an RBC transfusion is exposed to donor plasma, white blood cells, and platelets; the potential contribution of these elements to RBC alloimmunization remains unclear. Much attention in recent years has been placed on recipient factors that influence RBC alloantibody responses. Danger signals, identified in murine and human studies alike as being risk factors for alloimmunization, may be quite diverse in nature. In addition to exogenous or condition-associated inflammation, autoimmunity is also a risk factor for alloantibody formation. Triggers for alloimmunization in pregnancy are not well-understood beyond the presence of a fetal/maternal bleed. Studies using animal models of pregnancy-induced RBC alloimmunization may provide insight in this regard. A better understanding of alloimmunization triggers and signatures of "responders" and "nonresponders" is needed for prevention strategies to be optimized. A common goal of such strategies is increased transfusion safety and improved pregnancy outcomes.
Topics: Animals; Blood Group Incompatibility; Erythrocytes; Female; Fetomaternal Transfusion; Humans; Immunization; Isoantibodies; Isoantigens; Mice; Pregnancy
PubMed: 27913514
DOI: 10.1182/asheducation-2016.1.446