Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention

Published version. Source at http://doi.org/10.1007/s00005-015-0371-9.Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000–1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway

Recommendations of the Polish Society of Gynecologists and Obstetricians regarding caesarean sections

In recent years, the worldwide percentage of deliveries by caesarean section has increased. However, this has only improved obstetric outcomes in low-income countries [1, 2]. Unfortunately, in Poland and other high-income countries, the rate of caesarean section, which is greater than 20%, is no longer associated with decreases in the perinatal mortality of mothers and their offspring. Currently in Poland, 43.85% of births are by caesarean section [3]. The increased number of caesarean sections may be associated with the development of perinatal medicine, and of diagnostics in particular, which can have an impact on the frequency of detecting foetal abnormalities. The results of randomised multicentre study carried out across various populations in the last two decades have indicated there is a greater risk to a child during vaginal delivery in cases of breech presentation [4]. Also, among women with one prior caesarean, planned elective caesarean section compared with planned vaginal birth was associated with a lower risk of fetal and infant death or serious infant outcome [5]. As a consequently, some national associations of obstetricians and gynecologists recommended the classification of pregnant women with these abnormalities for elective caesarean section. Epidemiological data from various populations indicate, however, that the main indications for caesarean section are still labour arrest and intrapartum fetal hypoxia [6, 7]

Fetal Cardiac Interventions—Polish Experience from “Zero” to the Third World Largest Program

This article presents the technical aspects of the Polish fetal cardiac interventions (FCI) program, including preparation of the team and modifications in the technique of the procedure that aim to increase its safety for the mother and the fetus. Over 9 years, 128 FCI in 113 fetuses have been performed: 94 balloon aortic valvuloplasties (fBAV), 14 balloon atrioseptoplasties (fBAS) with stent (BAS+), 5 balloon atrioseptoplasties without stent placement (BAS−), and 15 fetal pulmonary valvuloplasties (fBPS). The technical success rate ranged from 80% (BAS−) to 89% (fBAV), while the procedure-related death rate (defined as death within 72 hours following the procedure) ranged from 7% (fBAV and fBPV) to 20% (BAS). There were 98 live births after all FCI (3 pregnancies continue). Median gestational age at delivery was 39 weeks in our center and 38 weeks in other centers

Effect of hAM CCM on HUVECs migration assayed by scratch test.

<p>There are results of 160 measurements, 8 independent assays with 10 measurements for test and control each. Median values and (P25, P75) are shown (n = 8, p < 0.05). Detailed description of the assay is in Material and methods.</p

Growth factors in hAM CCM.

<p>Forty-one growth factors were quantitated by antibody array and the obtained values were combined into following growth factor families: EGF family (EGF-2, HB-EGF, EGF-R); FGF family (bFGF, FGF-4, FGF-6, FGF-7); Hematopoietic factors HF (MCSF, MCSF-R, SCF, SCF-R); IGF family (IGF-1, IGF-2, IGF-1SR); IGFBP family (IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6); Neurotrophic factors NF (bNGF, GDNF, NT-3, NT-4); PDGF family (PDGF-AA, PDGF-AB, PDGF-BB, PDGF-Ra, PDGF-Rb); TGF family (TGF-α, TGF-β, TGF-β2, TGF-β3); Vasculogenic factors VF (PLGF, VEGF, VEGF-R3, VEGF-D, VEGF-R2); some growth factors are presented separately: AR; G-CSF; GM-CSF; HGF. Each growth factor fluorescence value (FV) was measured and calculated as described in Materials and methods. (n = 4) (p < 0.05).</p

The example of real time migration assay of stimulated and controlled HUVECs directly from the X-Celligence system.

<p>The assay was repeated seven times with similar result during 25h observation at 37^°C. The difference between migration curves for cells in cultures with presence of hAM CCM and in control medium was significant. (p < 0.05).</p

Effect of hAM CCM on chemotaxy indeks of BM MNCs.

<p>The chemotaxy index (CI) after 2.5 h at 37^°C incubation time was calculated by dividing the number of cells in lower chamber by the number of cells added to the upper chamber counted at the start of the test. Median values and interquartile range (P25, P75) are shown (n = 12, p < 0.05).</p

Effect of hAM CCM on HUVECs expression of cell adhesion molecule-1 (CD31) marker.

<p>Significantly lower expression is observed in presence of hAM CCM. Median values and interquartile ranges (P25, P75) are shown (n = 3, p < 0.05).</p