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Fetal alloimmunization

Marta Ferro, Hada C Macher, Pilar Noguerol, Pilar Jimenez-Arriscado, Patrocinio Molinero, Juan M Guerrero, Amalia Rubio
Fetal and Neonatal alloimmune thrombocytopenia (FNAIT) is a condition which could occur when pregnant women develop an alloimmunization against paternally inherited antigens of the fetal platelets. Approximately 80 % of FNAIT cases are caused by anti-HPA-1a, about 15 % by anti-HPA-5b and 5 % by other HPA antibodies. Only 2 % of the total population is HPA-1a negative (HPA-1b1b). The HPA-1a allele differs by one single nucleotide from HPA-1b allele, yet it represents around 27 % of total severe thrombocytopenias...
2016: Advances in Experimental Medicine and Biology
Susanna Sainio, Kaija Javela, Jarno Tuimala, Katri Haimila
Lack of reliable laboratory parameters is the main challenge in the management of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Despite the long-known association between the HLA-DRB3*01:01 allele and human platelet antigen 1a (HPA-1a) alloimmunisation, maternal human leucocyte antigen (HLA) typing has been of little clinical value. Recently, other DRB3 allele variants have been suggested to predict the severity of FNAIT. In this nationwide population-based retrospective cohort study, we performed extensive HLA typing of 96 women, accounting for 87% of our cohort of 110 families with confirmed or possible HPA-1a-immunisation...
October 17, 2016: British Journal of Haematology
Hannah B Anastasio, Maureen Grundy, Meredith L Birsner, Karin J Blakemore
BACKGROUND: Gestational alloimmune liver disease, a form of profound liver failure in the newborn, is the main underlying cause of the entity formerly known as neonatal hemochromatosis. Antepartum maternal intravenous immunoglobulin (IVIG) has been shown to prevent gestational alloimmune liver disease, which otherwise has a recurrence risk above 90% in subsequent pregnancies. CASE: A 30-year-old woman, gravida 3 para 0120, presented early in gestation. Her previous pregnancy had been complicated by fetal growth restriction, oligohydramnios, and ultimately fatal fulminant neonatal liver failure...
October 6, 2016: Obstetrics and Gynecology
Marije M Kamphuis, Heidi Tiller, E S van den Akker, Magnus Westgren, Eleonor Tiblad, Dick Oepkes
OBJECTIVE: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). METHODS: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome...
October 12, 2016: Fetal Diagnosis and Therapy
Carolien Zwiers, Irene T M Lindenburg, Frans J C M Klumper, Masja de Haas, Dick Oepkes, Inge L van Kamp
BACKGROUND: maternal alloimmunization to fetal red blood cell antigens is a major cause of fetal anemia, which in untreated cases can lead to hydrops and perinatal death. The cornerstone of the management during pregnancy is intrauterine intravascular blood transfusion. Although this procedure is considered to be relatively safe, (procedure-related) complications continue to occur. OBJECTIVES: to evaluate procedure-related complications and perinatal loss rates of intrauterine transfusion and changes over time, aiming to identify factors leading to improved outcome...
October 5, 2016: Ultrasound in Obstetrics & Gynecology
Maria Therese Ahlen, Anne Husebekk, Ida Løken Killie, Bjørn Skogen, Tor Brynjar Stuge
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a pregnancy-related condition caused by maternal antibodies binding an alloantigen on fetal platelets. In most cases the alloantigen is formed by a single amino acid, integrin β3 Leu33, referred to as human platelet antigen-1a (HPA-1a). Production of anti-HPA-1a antibodies likely depends on CD4(+) T cells that recognize the same alloantigen in complex with the HLA-DRA/DRB3*01:01 molecule. While this complex is well characterized, T cell recognition of it is not...
September 8, 2016: JCI Insight
S Ronzoni, J Keunen, D Arnold, J Smith, G Ryan
No abstract text is available yet for this article.
September 2016: Ultrasound in Obstetrics & Gynecology
Whitney A McCarthy, Edwina J Popek
Fetal anemia and hydrops may be caused by parvovirus B19 infection and maternal alloimmunization to RhD with subsequent hemolytic disease of the fetus and newborn. The use of intrauterine transfusion over the last few decades has dramatically improved outcomes. Prior literature has extensively documented placental changes associated with untreated parvovirus infection and RhD HDFN in intrauterine fetal demises (IUFD) and pre-term births; however, histopathologic changes in term placentas from term infants treated with IUT have not been reported...
September 19, 2016: Pediatric and Developmental Pathology
Ying-Jan Weng, Anne Husebekk, Björn Skogen, Mette Kjaer, Liang-Tzung Lin, Thierry Burnouf
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed...
2016: PloS One
Madhavi Lakkaraja, Jenny C Jin, Karen C Manotas, Cheryl A Vinograd, Polina Ferd, Julia Gabor, Megan Wissert, Richard L Berkowitz, Janice G McFarland, James B Bussel
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...
October 2016: Transfusion
Gabriella Martillotti, Francoise Rypens, Michele David, Nancy Catalfamo, Johanne Dubé, Catherine Taillefer, Christian Lachance, François Audibert
INTRODUCTION: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition that may lead to intracerebral haemorrhage (ICH) in the fetus or neonate. Platelet alloimmunisation causing FNAIT has been described in association with fetal cerebral ventriculomegaly (VM), presumably due to subclinical ICH. The objective of this study was to assess the association between fetal VM and platelet alloimmunisation. METHODS: This is a case series of pregnancies with fetal VM screened for platelet alloantibodies from 2003 to 2012...
September 7, 2016: Fetal Diagnosis and Therapy
Mariela Granero Farias, Suzane Dal Bó, Simone Martins de Castro, Aline Reis da Silva, Joyce Bonazzoni, Luciana Scotti, Sergio H Almeida Martins Costa
Accurate detection and quantitation of fetomaternal hemorrhage (FMH) is critical to the obstetric management of rhesus D alloimmunization in Rh-negative pregnant women. The flow cytometry is based on the detection of fetal red blood cells using a monoclonal anti-HbF antibody, and is the method most indicated for this estimation. The objective of this study was to quantify fetal red blood cell levels of pregnant women using flow cytometry. We analyzed 101 peripheral blood samples from Rh-negative and Rh-positive women, whose mean age was 24 years (20-32 years), after vaginal delivery or cesarean section...
August 5, 2016: Fetal and Pediatric Pathology
Kassie J Hyde, Danny J Schust
Characterization of the implanting human fetus as an allograft prompted a field of research in reproductive immunology that continues to fascinate and perplex scientists. Paternal- or partner-derived alloantigens are present in the maternal host at multiple times during the reproductive process. They begin with exposure to semen, continue through implantation and placentation, and may persist for decades in the form of fetal microchimerism. Changes in maternal immune responses that allow allogenic fertilization and survival of semiallogenic concepti to delivery must be balanced with a continued need to respond appropriately to pathogenic invaders, commensals, cell or tissue damage, and any tendency toward malignant transformation...
September 1, 2016: Fertility and Sterility
Giuseppina Perrone, Roberto Brunelli, Eleonora Marcoccia, Ilaria Zannini, Miriam Candelieri, Maria Gozzer, Claudia Stefanutti
Therapeutic apheresis (TA) is a complex extracorporeal procedure for the treatment of several acute and chronic diseases. TA in pregnancy is considered safe for both mother and fetus and has the same indications of non-pregnant patients. TA can be used during the entire course of the pregnancy with the following purposes: (i) to treat several maternal acute and chronic conditions; (ii) to treat fetal conditions; (iii) to avoid administration of drugs potentially harmful to the fetus; and (iv) to reach a more advanced gestational age in order to prevent fetal prematurity...
July 14, 2016: Therapeutic Apheresis and Dialysis
Jeanne E Hendrickson, Meghan Delaney
Red blood cell (RBC) sensitization occurs in some women in response to exposure to paternally derived RBC antigens during pregnancy or to nonself antigens on transfused RBCs during their lifetime. Once sensitized, future pregnancies may be at risk for hemolytic disease of the fetus and newborn. Although great strides have been made over the past few decades in terms of identifying blood group antigens and in predicting fetal anemia through the use of noninvasive monitoring, many questions remain in terms of understanding RBC alloimmunization risk factors, preventative therapies, and treatment strategies...
October 2016: Transfusion Medicine Reviews
Marije Kamphuis, Noortje Paridaans, Dian Winkelhorst, Agneta Wikman, Eleonor Tiblad, Enrico Lopriore, Magnus Westgren, Dick Oepkes
BACKGROUND: Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose-finding study. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG. STUDY DESIGN AND METHODS: We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH)...
September 2016: Transfusion
Sentot Santoso, Hevi Wihadmadyatami, Tamam Bakchoul, Silke Werth, Nadia Al-Fakhri, Gregor Bein, Volker Kiefel, Jieqing Zhu, Peter J Newman, Behnaz Bayat, Ulrich J Sachs
OBJECTIVE: Fetal/neonatal alloimmune thrombocytopenia is a severe bleeding disorder, which can result in intracranial hemorrhage (ICH), leading to death or neurological sequelae. In whites, maternal anti-human platelet antigen-1a (HPA-1a) antibodies are responsible for the majority of cases. No predictive factors for ICH are available to guide prophylactic treatment during pregnancy. In this study, we investigated antibodies from mothers with ICH-positive fetal/neonatal alloimmune thrombocytopenia and with ICH-negative fetal/neonatal alloimmune thrombocytopenia to identify serological and functional differences between the groups...
August 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Xiaohong Ruby Xu, Dan Zhang, Brigitta Elaine Oswald, Naadiya Carrim, Xiaozhong Wang, Yan Hou, Qing Zhang, Christopher Lavalle, Thomas McKeown, Alexandra H Marshall, Heyu Ni
Platelets are small anucleate blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. At the site of vascular injury, platelet adhesion, activation and aggregation constitute the first wave of hemostasis. Blood coagulation, which is initiated by the intrinsic or extrinsic coagulation cascades, is the second wave of hemostasis. Activated platelets can also provide negatively-charged surfaces that harbor coagulation factors and markedly potentiate cell-based thrombin generation...
December 2016: Critical Reviews in Clinical Laboratory Sciences
Florentine F Thurik, Godelieve C M L Page-Christiaens, Aicha Ait Soussan, Peter C Ligthart, Goedele M A F Cheroutre, Bernadette Bossers, Barbera Veldhuisen, C Ellen van der Schoot, Masja de Haas
BACKGROUND: Fetal RHD genotyping allows targeted diagnostic testing, fetal surveillance, and eventually intrauterine treatment to D-alloimmunized pregnant women who carry an RHD+ fetus. However, false-positive and false-negative results of noninvasive prenatal fetal RHD genotyping have been described due to a variety of causes. In this case report we present two cases where noninvasive fetal RHD typing was complicated by a previous bone marrow transplantation (BMT). CASE REPORT: We describe two women with a history of allogeneic BMT in early childhood...
August 2016: Transfusion
Xiaohong Ruby Xu, Reid C Gallant, Heyu Ni
Platelets are small versatile blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. Platelet accumulation (adhesion and aggregation) at the site of injury has been considered the first wave of hemostasis. Interestingly, although fibrinogen and von Willebrand factor (VWF) are documented to be essential for hemostasis, fibrinogen/VWF-independent platelet aggregation and thrombosis still occur. Following platelet activation and phosphatidylserine expression, platelets also contribute to cell-based thrombin generation and blood coagulation - the second wave of hemostasis...
May 2016: Thrombosis Research
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