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Erythroblastosis Fetalis [keywords]
- [Maternal blood intrauterine transfusions in the therapy of red-cell alloimmunization performed in three difficult cases]. [Case Reports, English Abstract, Journal Article]
- Ginekol Pol 2014 Sep; 85(9):703-7.
Maternal alloimmunization can lead to hemolytic anemia, hydrops fetalis and even fetal or neonatal death. Intrauterine treatment is possible and effective even though it is associated with some risk. We present a rare method of maternal blood intrauterine transfusions in the therapy of three difficult cases of erythroblastosis fetalis. The aim of this report was to present an alternative to volunteer donors. In severe cases, i.e. in the absence of matching blood types from the donor in the presence of multiple alloantibodies in the pregnant woman or if multiple transfusions are required, this can be the only therapeutic option. To the best of our knowledge, this has been the first publication on maternal blood donation for intrauterine transfusion in the Polish literature.
- Feto-maternal haemorrhage assessment in a woman with a large population of red blood cells containing fetal haemoglobin. [Case Reports, Journal Article, Research Support, Non-U.S. Gov't]
- Ginekol Pol 2014 Aug; 85(8):614-8.
FMH quantification is necessary to calculate an individual dose of prophylactic anti-RhD immunoglobulin and to diagnose fetal anaemia causes. We encountered a healthy woman with a numerous RBCs containing fetal haemoglobin (HbF).To investigate the cause of this sign and the correct evaluation of fetal RBCs in maternal circulation.Patients samples and artificial mixtures were tested by microscopic Kleihaur-Betke (KB) and flow cytometric (FC) tests with anti-HbF + anti-CA (carbonic anhydrase), and with anti-D. The patient's blood count with reticulocyte parameters, and concentration of bilirubin, haptoglobin, iron, transferrin, ferritin, hepcidin, sTR, HbF, HbA2 were measured. Genes coding the beta- and gamma-globin were sequenced.It was impossible to distinguish the population of fetal and maternal HbF positive cells using KBT and FC with anti-HbF. Application of anti-CA and anti-D allowed to separate them. Maternal blood haematological and biochemical parameters were normal but HbF was 3.3% of total Hb concentration (normal < 1%). There were no mutations in the beta- and gamma-globin genes, but Xmn I polymorphism at -158 position in gamma-globin gene was detected in the homozygous state.A very large population of HbF positive cells sometimes can be detect in a healthy woman. Implementation of the various procedures for FMH assessment is necessary in the such case, otherwise, the detection of fetal erythrocytes may not be possible or can give false results.
- Transient neonatal hyperinsulinism with adaptation disorders: a report of three cases. [JOURNAL ARTICLE]
- J Pediatr Endocrinol Metab 2014 Aug 22.
Abstract Transient hyperinsulinism can occur in neonates following exposure to perinatal stress, such as intrauterine growth restriction and birth asphyxia. However, little is known about its pathophysiology and clinical manifestations. We report three neonatal cases of transient severe hyperinsulinism complicated with cardiopulmonary problems, thrombocytopenia, and marked erythroblastosis at birth. All cases showed signs of placental insufficiency, indicating that chronic hypoxia and malnutrition during fetal development might be associated with characteristic clinical features after birth. Perinatal stress-associated hyperinsulinism can be regarded as a systemic syndrome characterized by cardiopulmonary and hematological problems due to fetal chronic hypoxia.
- CD15 - A new marker of pathological villous immaturity of the term placenta. [JOURNAL ARTICLE]
- Placenta 2014 Aug 12.
Idiopathic immaturity is one of the main reasons for latent placental insufficiency and antenatal hypoxia. Postnatal identification of the immature placental phenotype may help early stratification of a heterogeneous population of newborns and individually identify risk of disease in the immediate postnatal life. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental immaturity.111 tissue samples from normal and pathological term placentas with persisting villous immaturity comprised the comparative immunohistochemical study (CD15, CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type.We have shown that pathological villous immaturity is attended by significantly increased CD15-expression in the macro- and microvascular endothelium compared with the normal placenta. CD34-expression was not different from that in normal placentas.This paper documents the correlation of CD15+ endothelium in the macrovascular fetoplacental vessels with a severe form of villous immaturity associated with fetal hypoxia/asphyxia and erythroblastosis. Increased CD15-expression only in the microvascular segment of the fetoplacental vessels correlated with moderate villous immaturity and was associated with GDM, idiopathic fetal macrosomia and nonspecific chronic villitis.We propose that "immature" CD15+ endothelium is an important diagnostic marker of persisting villous immaturity and chronic placental dysfunction. The level of CD15 expression in the macro- and microvasculature reflects the degree of pathological placental villous immaturity.
- Changes in middle cerebral artery velocimetry of fetuses diagnosed postnatally with mild or moderate hemolytic disease. [JOURNAL ARTICLE]
- Acta Obstet Gynecol Scand 2014 Aug 21.
To determine the longitudinal trends of middle cerebral artery peak systolic velocity (MCA PSV) in fetuses with mild or moderate hemolytic disease according to the need of postnatal therapy.Prospective cohort study.University referral center.Twenty-three fetuses from singleton alloimmunized pregnancies.Serial measurements of MCA PSV were performed. After delivery, newborns were grouped by the need for postnatal management into mild hemolytic disease which required no or only phototherapy (n=14, group 1), and moderate hemolytic disease, where postnatal top-up or exchange transfusions were required (n=9, group 2).Serial Doppler MCA PSV data transformed to multiples of the median, analyzed with linear regression and exponential models.We performed 83 measurements in group 1: 3-8 per fetus; mean GA at inclusion, 23 weeks and 65 measurements in group 2: 4-15 per fetus; mean GA at inclusion, 22 weeks. The estimated mean slopes of the MCA PSVs increased with the degree of postnatal therapy required (group 1: MCA PSV = 0.003 GA + 1.298; group 2: MCA PSV = 0.035 GA + 0.436). The relative average increments (RAI) were 4.7% and 7.1%, respectively. The two groups exhibited significant differences in mean slope and RAI (p<0.05).Fetuses that required postnatal transfusions due to hemolytic disease showed an enhanced progressive increase in MCA PSVs compared to those without transfusion requirement. This information might enable their identification during pregnancy. This article is protected by copyright. All rights reserved.
- Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia. [Journal Article]
- Lymphology 2014 Mar; 47(1):28-39.
We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment. Lymphoscintigraphy is safe and useful in the diagnosis of lymphatic dysplasia in the newborn and children. Moreover, it is well tolerated by patients and well accepted by their parents.
- Immunotoxicity assessment of rice-derived recombinant human serum albumin using human peripheral blood mononuclear cells. [Journal Article]
- PLoS One 2014; 9(8):e104426.
Human serum albumin (HSA) is extensively used in clinics to treat a variety of diseases, such as hypoproteinemia, hemorrhagic shock, serious burn injuries, cirrhotic ascites and fetal erythroblastosis. To address supply shortages and high safety risks from limited human donors, we recently developed recombinant technology to produce HSA from rice endosperm. To assess the risk potential of HSA derived from Oryza sativa (OsrHSA) before a First-in-human (FIH) trial, we compared OsrHSA and plasma-derived HSA (pHSA), evaluating the potential for an immune reaction and toxicity using human peripheral blood mononuclear cells (PBMCs). The results indicated that neither OsrHSA nor pHSA stimulated T cell proliferation at 1x and 5x dosages. We also found no significant differences in the profiles of the CD4+ and CD8+ T cell subsets between OsrHSA- and pHSA-treated cells. Furthermore, the results showed that there were no significant differences between OsrHSA and pHSA in the production of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and IL-4. Our results demonstrated that OsrHSA has equivalent immunotoxicity to pHSA when using the PBMC model. Moreover, this ex vivo system could provide an alternative approach to predict potential risks in novel biopharmaceutical development.
- [Haemolytic disease of the fetus and newborn/HDFN/timing in pregnant women and prophylaxis]. [English Abstract, Journal Article]
- Akush Ginekol (Sofiia) 2014; 53(2):58-63.
Haemolytic disease of the fetus and newborn/HDFN/is a condition in which the lifespan of the fetal or newborn infants red cells is shortened by the action of maternal antibodies against antigens present on the infants red cells. The most common routes of maternal sensitization are via blood transfusion or fetomaternal hemorrhage. With the institution of antenatal Rhesus (Rh) D immunoglobulin prophylaxis, the frequency of maternal alloimmunization in Rh D-negative women has decreased significantly. The prevention and treatment of Rh D alloimmunization is a true success story in obstetrics. This article present the reasons for the persistence of the anti-D alloimmunization, protocol for the prevention and diagnosis of HDFN, immunohematological management of all pregnant women, critical titre, protocol and timing in alloimmunized pregnant women.
- Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. [JOURNAL ARTICLE]
- Br J Haematol 2014 Jun 7.
Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (FcγR). Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. This suggests that other factors are involved in the pathogenesis of HDFN. Binding of IgG to FcγR requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). The degree of anti-D fucosylation correlated significantly with CD16 (FcγRIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human FcγRIIIa. Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential.