Intrauterine Transfusion Research Articles

Racial/ethnic disparities among women receiving intrauterine transfusions for alloimmunization at a single fetal treatment center.

Disparities are prevalent in numerous areas of healthcare. We sought to investigate whether there were racial/ethnic disparities among pregnant women with the most severe form of alloimmunization who require intrauterine transfusions (IUT). We reviewed patients who underwent IUT for alloimmunization at a single fetal treatment center between 2015 and 2020. This "IUT cohort" was compared to an "Alloimmunization cohort": patients seen at our institution with a diagnosis of alloimmunization during pregnancy, who did not receive IUT. We collected maternal demographics including self-identified race/ethnicity and primary language, transfusion, and antibody characteristics. The cohorts were compared using unpaired t-tests, Mann-Whitney tests, and Fischer's exact tests, as appropriate. The IUT cohort included 43 patients and the alloimmunization cohort included 1049 patients. Compared to the alloimmunization cohort, there were significantly more patients of Latina descent in the IUT cohort (23.3% vs. 3.4%, p < .0001), and more non-English speakers (18.6% vs. 4.6%, p=.001). Twenty-one percent (9/43) of patients had immigrated to the United States, all of whom had pregnancies or miscarriages in their country of origin. A third of patients had new antibodies identified on serial screens during the current pregnancy. Significantly more women of Latina ethnicity and non-English speakers required IUTs compared to the cohort of women with alloimmunization. Insufficient access to care prior to arriving in the United States and among racial and ethnic minorities in the United States may contribute to these findings. Providers should be cognizant of potential, racial, and ethnic inequalities among women receiving intrauterine transfusions.

Fetal procedures during COVID-19 pandemic: Challenges in a newly developing centre

Prenatal invasive diagnostic and therapeutic procedures have drastically reduced during COVID-19 pandemic. Unlike routine prenatal care, these are time bound and highly skilled procedures available at specialized centres. This adds to the limited accessibility for at-risk women. Major concerns including procedure related risk, exposure of health care personnel and vertical transmission of COVID-19. At newly developing tertiary centre, we had done 36 fetal procedures during pandemic including 25 amniocentesis, three chorion villus sampling and eight intrauterine transfusions. It is advisable to perform life-saving fetal interventions irrespective of COVID-19 status taking full precautions and proper counselling of women.

Effect of intravenous immunoglobulins to postpone the gestational age of first intrauterine transfusion in very severe red blood cell alloimmunization: A case-control study

BackgroundEarly intrauterine transfusion (IUT) is associated with a higher risk of fetal loss. Our objective was to evaluate the efficiciency of intravenous immunoglobulins (IVIG) to postpone the gestational age at first IUT beyond 20 weeks of gestation (WG) compared to the previous pregnancy in case of very severe red blood cell (RBC) alloimmunization. Study design and methodsVery severe RBC alloimmunization was defined by a high titer of antibodies and a previous pregnancy complicated by a first IUT before 24 WG and/or perinatal death directly related to alloimmunization.We performed a single-center case-control study. Cases and controls were patients respectively treated with weekly IVIG infusions started before 13 WG, and without. ResultsTwenty cases and 21 controls were included. Gestational age (GA) at first IUT was postponed after 20 WG in 18/20 (90 %) of patients treated with IVIG and in 15/21 (71 %) in the control group (p = 0.24). Compared to the previous pregnancy, the GA at first IUT was postponed by a median of 22 [+11; +49] days in the IVIG group and occurred in average 2 days earlier [-17 ; +12] in the non-treated group (p = 0.02). There was no difference between number of IUT and need for exchange-transfusion. IVIG treatment was associated with a significant decrease of antibodies' quantitation. ConclusionIn our series, IVIG tends to differ first IUT beyond 20 WG and have a significant effect in postponing the gestational age of the first IUT in patients with very severe RBC alloimmunization.

Nationwide survey of intrauterine blood transfusion for fetal anemia in Japan.

The present study investigated the current situation regarding intrauterine blood transfusion (IUT) for fetal anemia in Japan. We conducted a nationwide, multicenter, retrospective cohort questionnaire survey for cases that underwent IUT from 2011 to 2015. The questionnaire required perioperative information, indications, details of the procedure, procedure-related complications, and neonatal morbidity. A total of 100 IUT procedures were performed in 66 cases at 19 institutions during the study period. The most frequent indication of IUT was complicated monochorionic diamniotic (MCDA) twins in 28 (42.4%) cases, followed by 16 (24.2%) cases of red-cell alloimmunization, and 10 (15.2%) cases of parvovirus B19 infection. IUT was performed through the umbilical cord in the vast of majority cases (92%). Bleeding from the IUT site was the most common adverse event (40%). Two cases (2%) underwent emergency cesarean section after the procedure. There were no cases of rupture of membrane or intrauterine infection after IUT. The neonatal survival rate was 77.3% in the 66 total cases and 64% in the hydrops cases. The neonatal survival rates in MCDA twins, red-cell alloimmunization, and parvovirus B19 infection were 75%, 93.8%, and 70%, respectively. IUT was performed for mainly three indications in Japan: MCDA twins, red-cell alloimmunization, and parvovirus B19 infection. The incidences of severe adverse events seemed very low. The outcomes after IUT were favorable with variations in survival rates according to indications. However, further studies with long-term follow-up will be required to assess the effectiveness of IUT, especially for complicated MCDA twins.

Delivery and neuraxial technique outcomes in patients with hemophilia and in hemophilia carriers: a systematic review.

Female carriers are more common than males with hemophilia and unrecognized factor VIII or IX deficiency is associated with intrauterine growth retardation, epidural hematomas, blood transfusion, and peripartum hemorrhage. A review was conducted to assess the evidence for professional society recommendations for > 50% factor levels during labor. Two searches of Pubmed, CINAHL, Cochrane, and Google Scholar were completed in October 2019. The first for case reports and series described neuraxial techniques in patients with hemophilia-regardless of sex, age, or pregnant status. The second for case reports and series described bleeding outcomes of parturients with hemophilia. Primary outcomes were diagnosis of neuraxial hematoma (first search) and postpartum bleeding complications (second search). Thirteen articles (n = 134) described neuraxial techniques in patients with hemophilia. Neuraxial hematoma with paraplegia occurred in 3/134 patients-all had a factor level of 1%. Nineteen articles (2712 deliveries in 2657 women) described bleeding outcomes. Postpartum hemorrhage occurred in 7.1% (193/2712) of deliveries, of which 60% necessitated blood transfusion. Postpartum bleeding complications were twice as likely (51.0% [25/49] vs. 25.6% [52/203], P < 0.001) with factor activity < 50%. Therefore, factor levels should be assessed and increased above 50% prior to neuraxial technique and delivery.Trial registration: PROSPERO 2018 CRD42018110215.

Are fetal bilirubin levels associated with the need for neonatal exchange transfusions in hemolytic disease of the fetus and newborn?

Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the clinical value of fetal bilirubin assessment is not well known, and the information is rarely used. We speculated that there could be a role for this measurement in predicting the need for neonatal exchange transfusion. This study aimed to evaluate the predictive value of fetal bilirubin for exchange transfusions in severe hemolytic disease of the fetus and newborn. A total of 186 infants with Rh alloantibody-mediated hemolytic disease of the fetus and newborn treated with one or more intrauterine transfusions at the Leiden University Medical Center between January 2006 and June 2020 were included in this observational study. Antenatal and postnatal factors were compared between infants with and without exchange transfusion treatments. The primary outcome was the fetal bilirubin levels before the last intrauterine transfusion in relation to the need for exchange transfusion. In a multivariate logistic regression analysis, the fetal bilirubin level before the last intrauterine transfusions (odds ratio, 1.32; 95% confidence interval, 1.09-1.61 per 1 mg/dL) and the total number of intrauterine transfusions (odds ratio, 0.63; 95% confidence interval, 0.44-0.91 per intrauterine transfusion) were independently associated with the need for exchange transfusion. The area under the curve was determined at 0.71. A Youden index was calculated at 0.43. The corresponding fetal bilirubin level was 5 mg/dL and had a sensitivity of 79% and a specificity of 64%. A high fetal bilirubin level before the last intrauterine transfusion was associated with a high likelihood of neonatal exchange transfusion.

Corticosteroids for management of Rh-isoimmunization, extended study in a tertiary referral centre.

Background: RhD isoimmunization is a life threatening condition for affected fetuses. It is currently treated only by intrauterine transfusion of packed red blood cells. This procedure required special skill and has potential complications.Aim : The aim of the present study was to evaluate the role of corticosteroids in prevention of fetal anemia due to RhD isoimmunization.Material and Methods: The study was conducted on 15 pregnant patients with RH isoimmunization in Shatby Maternity University Hospital, Alexandria, Egypt, during the period from July 30th 2016 to July 30th 2019. Recruited women received 40 mg oral prednisolone starting from 10th week of gestation. Follow up of Anti-Rh antibodies titer and-from 18 weeks gestation- middle cerebral artery peak systolic velocity (MSA-PSV) was done every 2 weeks. Patients were delivered at 34 weeks gestation by elective caesarean section after receiving 4 doses of dexamethasone to enhance fetal lung maturity.Results: 12 patients continued the trial. Significant reduction was achieved in anti-Rh antibodies titer. Reduction in MSA-PSV was achieved and maintained below 1.5 MOM. Gestational age at delivery ranged from30.3-34 weeks (33.18±1.2 weeks). Fetal eight at delivery ranged from 1550-2270 grams (1978.5±232.5 gm). 9 newborns required NICU admission, only 2 newborns underwent exchange transfusion therapy.Conclusion: In Rh iso-immunization, oral prednisolone proved to have a good rule in preventing fetal anemia and introducing its use should be considered. More studies with bigger sample size are needed to confirm its efficacy

Our Experience of Immune Fetal Hydrops: its Clinical Characteristics and Perinatal Outcome.

Fetal hydrops is a serious condition which has high morbidity and mortality. Incidences of immune hydrops have decreased by manifold after introduction of anti-D immunoglobulin. Intra-uterine fetal blood transfusion revolutionized the treatment of these affected fetuses after diagnosis of immune fetal hydrops. In this study we aim to evaluate the clinical characteristics of immune hydropic fetuses and perinatal outcome after institution of intra-uterine transfusions. A retrospective study was carried out in pregnant women with immune fetal hydrops from October 2004 to December 2019 in our tertiary care hospital. After diagnosis of fetal hydrops, all the fetuses received intra-uterine transfusions. All the newborns were followed up till 3months postdelivery. All the fetuses were divided in two groups: hydrops diagnosed below 32weeks (Group A) and in second group hydrops diagnosed after 32weeks gestation (Group B). Total 63 patients were diagnosed to have hydrops during the study period. Group A had 48 fetuses and Group B had 15 fetuses. Average gestational age of diagnosis of hydrops in group A was 24.2weeks and in group B it was 32.5weeks. All the fetuses received intra-vascular intra-uterine transfusion. Pericardial effusion was found to be significantly associated with group A. Successful perinatal outcome was seen in 92% fetuses. 87% fetuses had complete resolution of hydrops before delivery. All the fetuses received phototherapy and intra-venous immunoglobulin after delivery, and 5 fetuses underwent exchange transfusion. Favourable perinatal outcome was achieved in hydropic fetuses with intra-uterine blood transfusions. Complete resolution of hydrops before delivery increases the chances of perinatal survival. The online version contains supplementary material available at 10.1007/s13224-020-01423-4.

792 Intrauterine transfusion practice patterns among members of the society for Maternal-Fetal medicine

To describe practice pattern among providers of intrauterine transfusion (IUT). In this cross-sectional study, maternal-fetal medicine specialists (MFM) were surveyed regarding their IUT practices. The survey was made available to members of the Society for Maternal-Fetal Medicine (SMFM) via posting on the SMFM website and via distribution through the SMFM Special Delivery email list. IUT survey questions included number performed annually, location of procedure, perioperative medications, maternal analgesia, fetal access site, and postoperative care. Data were reported using descriptive statistics. A total of 51 respondents completed the survey. The majority (75%) reported an institutional rate of fewer than 10 IUT per year. The majority (81%) responded that fewer than 5 MFM perform IUT at their institution. While most IUT occur in the operating room (78% viable and 49% previable), previable cases were more likely to occur elsewhere when compared to viable cases (34% vs 14% in Labor/Delivery room; 17% vs 7% in ultrasound suite). There were a variety of responses regarding perioperative use of tocolytics, antibiotics, paralytics, and steroids (Figure 1). Of the 41 who provided information about immediate postoperative care, most reported a minimal fetal monitoring period of a few hours after the procedure, with only 9 (22%) reporting universal admission for extended overnight monitoring. The most commonly reported fetal access site was the placental cord insertion (PCI), followed by a free loop of cord (Figure 2). There appears to be a wide range of IUT-specific practices among IUT-performing members of SMFM. Consideration should be given to convening an expert panel to review the available evidence and provide a list of best practices for IUT. Additional topics to address include frequency of ultrasound monitoring following first IUT, threshold for repeating IUT, and latest gestational age to perform IUT. Querying blood bank personnel regarding IUT-specific preparation of blood products should be another focus of future research.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

432 To determine the rate of decline of fetal hemoglobin following an intrauterine blood transfusion

Hemolytic disease of the fetus and newborn (HDFN) is characterized by fetal anemia, secondary to maternal alloantibody-mediated fetal erythrocyte destruction. While RhD immunoprophylaxis has reduced the requirement for intrauterine blood transfusion (IUT), this procedure remains the cornerstone of treatment for severe fetal anemia. The objective of this study was to calculate the rate of daily decline in fetal haemoglobin (FHb) following IUT for fetal anemia. This was a retrospective review of all patients who underwent IUT for fetal anemia at the National Maternity Hospital, Dublin, a tertiary referral centre, over a 10-year period (2011-2020). Data was analysed and the rate of daily decline was calculated for those after one, two and three IUT procedures. Results are presented in Table 1. A total of 98 intrauterine blood transfusions were performed in 46 fetuses, of which 31/98 (67%) and 16/98 (34.7%) required a second and a third IUT, respectively. The median gestational age (GA) at first IUT was 29+1 weeks (range 17+2-34+5 weeks), and the median GA at second IUT was 29+2 weeks (range: 22+0-34+4 weeks). The median rate of decline in FHb between first and second IUT was 0.442g/dl/day (range: 0.12-1.03g/dl/day). The median GA for a third IUT was 32 weeks (range: 26+2-34+5 weeks). The rate of decline in FHb level between the second and third IUT was 0.291g/dl/day (range: 0.16-0.43g/dl/day). Only 5/98 (10.8%) of cases required a fourth IUT at a median GA of 31+4 weeks (range 30+0-34+0 weeks), with a rate of decline of 0.26g/dl/day (range 0.217-0.317g/dl/day). No fetal or maternal mortality was observed in our series. This study provides guidance as to the rate of FHb decline post a varying number of IUT procedures, and observed a reducing rate of decline following successive transfusions. It also highlights the significant range of decline that exists between patients. Careful fetal monitoring between transfusions must remain a vital part of the management of HDFN.

Pregnancy management tactics in fetal hemolytic disease. Literature review

Hemolytic disease of the fetus is one of the types of pathological abnormalities in the development of the fetus, the reason of which is isoimmune hemolytic anemia. Depending on the degree of severity of this pathology, it can influence the development of the fetus both in a mild form, practically leaving no trace and in a severe form, which can cause fetal death.&#x0D; When carrying out a timely diagnostic research to detect this pathology, tactics of pregnancy management should differ, that will allow maintaining of pregnancy and ensure normal development of the fetus just until the moment of childbirth. To determine the tactics, which will be used during pregnancy management, it is necessary to identify not only the symptoms of hemolytic diseases of the fetus but its degree as well. Depending on the degree of severity of this disease, the activities will differ. If the disease is developing in a mild form, a pregnant woman is thoroughly observed and repeatedly diagnosed; if it is a severe form, intrauterine fetal blood transfusions are regularly conducted. The tactics of managing pregnancy with the detected fetal hemolytic disease will differ from the standard one and its right choice will ensure normal development of the fetus and term labor with minimum risks for both a mother and a child.

Синдром анемии-полицитемии – современные подходы к диагностике и антенатальной коррекции

Twin anemia polycythemia sequence (TAPS) is a specific complication of the monochorionic multiple birth, which is based on chronic feto-fetal blood transfusion over placental vascular anastomoses, and the main clinical symptom is discordant fetal hemoglobin level in the absence amniotic fluid imbalance. Currently, there is no generally recognized consensus on the optimal treatment tactics. Dynamic observation, labor, intrauterine blood transfusion, selective fetocide, fetoscopic laser coagulation of placental vascular anastomoses are applied, although the latter is recognized by the majority of researchers as the most promising method for treating TAPS. There are disagreements in estimating the frequency of perinatal morbidity and mortality during pregnancy, complicated by the development of TAPS, and their real value has not yet been completely defined. Key words: intrauterine transfusion, Solomon method, monochorionic twins, twin anemia polycythemia sequence, fetoscopic laser coagulation

Immunization against αIIbβ3 and αvβ3 in Glanzmann thrombasthenia patients carrying the French Gypsy mutation

Unlabelled Box AbstractBackgroundGlanzmann thrombasthenia (GT) is a rare bleeding disorder caused by the absence or the dysfunction of the platelet αIIbβ3 integrin. A founder mutation in the ITGA2B gene was previously identified in French Gypsy patients. Interestingly, this mutation was strongly linked to the human platelet antigen‐1b (HPA‐1b). The HPA‐1bb Gypsy patients are at risk of isoimmunization against αIIbβ3, as this complex is not expressed at their platelet surface. Tentatively, they would, however, not have an increased risk of developing anti‐HPA‐1a alloantibodies by exposure of αIIbβ3 on platelets from random platelet transfusions. However, the β3 chain can also associate with the αv subunit expressed at the platelet surface. Because Gypsy GT patients express normal αvβ3 carrying HPA‐1b epitopes, these patients might develop anti‐HPA‐1a alloantibodies reacting with αvβ3 and/or β3. Objectives/Patients/MethodsTo demonstrate this hypothesis, sera from HPA‐1bb (n = 5) and HPA‐1ab (n = 1) Gypsy GT patients were investigated by modified antigen capture assay using platelets or stable transfected cells. Furthermore, stable transfected cells expressing either αIIbβ3 or αvβ3 together with soluble monomeric chimeric β3 (as absorbent) were used to differentiate anti‐β3 and anti‐αvβ3 reactivity. ResultsOnly HPA‐1bb patients developed alloantibodies reacting with HPA‐1a cells. Further analysis showed that HPA‐1bb patients developed anti‐HPA‐1a alloantibodies reacting with β3 and/or αvβ3. ConclusionIn this study, we found that HPA‐1bb patients who failed to express αIIbβ3 on the platelet surface can develop alloantibodies against HPA‐1a reacting with β3 as well as αvβ3. This is of particular importance as anti‐HPA‐1a alloantibodies might cause fetal neonatal alloimmune thrombocytopenia and/or platelet transfusion refractoriness.

Multiple intrauterine transfusions in case of rhesus alloimmunization and severe forms of hemolytic disease of the newborn

Multiple intrauterine transfusions in case of rhesus alloimmunization and severe forms of hemolytic disease of the newborn

Intrauterine Blood Transfusion in an HCV and HIV Co-Infected Woman

Abstract Hepatitis C infection is not uncommon in pregnant women. Vertical transmission of the virus from mother to fetus is estimated at 4%-8%, however this transmission rate is significantly higher when the mother is co-infected with HIV. Intrauterine blood transfusions can be a necessary part of management for certain perinatal conditions like hemolytic disease of the fetus. Currently there is no published material available on the vertical transmission risk of HCV infection to the fetus as a result of this procedure, irrespective of HIV co-infection. We present a case of a pregnant woman co-infected with HCV and HIV that required an intrauterine blood transfusion during pregnancy. Vertical transmission of either infection to the child did not occur. This provides important evidence that vertical transmission of HCV and/or HIV does not necessarily occur with intrauterine blood transfusions.

Maternal Red Blood Cell Alloimmunization Managed with Intrauterine Blood Transfusion: Predictors of Poor Outcome

Background: The rhesus (Rh) and Kell blood group systems are the most common of over 50 different antigens capable of causing maternal red blood cell (RBC) alloimmunization and severe fetal hemolytic disease. Anti-K and anti-D are responsible for a significant proportion of fetal anemia requiring intrauterine transfusion (IUT). Whilst IUT of packed RBCs improves neonatal survival and morbidity, clinical prognostic indicators are lacking. Our primary objective was to identify predictors of adverse outcome. Methods: We conducted a retrospective single-center study at Mount Sinai Hospital (MSH), Toronto, Canada. All pregnant patients alloimmunized with anti-K and anti-D as a single antibody, between 1991 and 2018 were included. Data were obtained from patient medical records, ultrasound reports and information from the transfusion medicine laboratory. Data included maternal demographics, antibody titers, pregnancy history, number of IUTs, hemoglobin (HB) concentration at the beginning and end of all IUTs. Neonatal outcomes included survival, mode of delivery, gestational age at delivery, birth weight, HB at birth and need for neonatal transfusion, phototherapy or intravenous immunoglobulins (IVIG). Our primary outcome was the composite outcome of stillbirth or neonatal death (SB/NND). We also constructed a secondary outcome consisting of top-up neonatal transfusion, exchange transfusion, phototherapy, or use of IVIG. Medians and interquartile ranges (IQR) or mean±SD were used as summary statistics and compared by Mann-Whitney or t-test; p&amp;lt;0.05 was statistically significant. Outcome predictors were identified using multivariable logistic or linear regression analysis; accounting for patient level clustering by marginal Generalized Estimating Equation did not significantly affect variables. Data were analyzed using SPSS. Results: 116 women with 128 pregnancies and 425 IUTs with anti-K or anti-D as a single antibody were identified. Median maternal age was 31 years (27.0-35.0) for anti-K and 32 years (23.6-40.6) for anti-D. The gestational age at 1st IUT differed significantly between anti-K and anti-D (24.3 vs 28.7 weeks respectively, p=0.004). Women with anti-K antibodies required more IUTs than women with anti-D (3.84 vs 3.12 IUTs, p=0.036) and HB at 1st IUT was significantly lower in the anti-K group (5.10 vs 7.05 g/dL, p=0.001) (Table 1). Following initiation of IUT, the time from 1st IUT to delivery was 69.6 days in the anti-K group and 54.6 in the anti-D group (p=0.06). The daily decrease of HB between 1st and 2nd IUT (as a marker of disease severity), development of fetal hydrops and severe preterm birth did not differ significantly between the two groups. Mean gestation age at delivery was 35.0 weeks in the anti-K and 36.0 weeks in the anti-D group (p=0.28), with 87.1% and 93.9% survival (p=0.37), respectively. The proportion of neonates requiring phototherapy, IVIG and exchange/top-up transfusion was comparable across the two antibody groups (Table 1). Regression analysis showed that delivery occurred sooner if HB dropped more rapidly between the first two IUTs (p=0.01). Each additional transfusion gained on average 22.5 days in utero (Table 2). In multivariable analysis, gestational age at 1st IUT was the only predictor of a SB/NND outcome (adjusted OR 0.79 [95%CI 0.67-0.93]; p=0.006). With 1st IUT at 23 weeks, the risk of SB/NND was 8%, but only 2.5% at 28 weeks and &amp;lt;0.01% at 36 weeks (Table 3). Gestational age at delivery (adjusted OR 1.11 [95%CI 1.00 to 1.23]; p=0.046) and HB at 1st IUT (adjusted OR 0.84 [95%CI 0.72 to 0.99]; p=0.038) were the only predictors of a composite adverse blood product requirement/intervention outcome (Table 4). The odds of blood product requirement/intervention postnatally at 1st IUT (median HB at 1st IUT of 6.6g/dL) at 28 weeks were 43% and increased by a further 38% for delivery at 34 weeks. Conclusion: The earlier in gestation that IUTs are implemented, the higher the odds of a SB/NND; however the later the gestation at delivery, the greater the odds of the neonate requiring blood products post-partum. The greater the HB drop between the 1st and 2nd IUT, the shorter the 'time between the first IUT and delivery', which increases the odds of a SB/NND outcome. Disclosures Garbowski: Vifor Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imara: Consultancy. Shehata:Ferring: Honoraria.

The Clinical Severity of Alpha-2 Globin Gene Variants: Homozygosity for Hb Agrinio (HBA2: c.89T>C) Leads to Severe Antenatal Anemia, about 8 Cases in 3 Families

Introduction: Hemoglobin (Hb) Agrinio (HBA2: c.89T&amp;gt;C (Leu29Pro) mutation) is a rare highly unstable Hb variant resulting from a leucine to proline substitution at codon29 of the alpha2-globin gene. Eleven homozygous cases of this non-deletional alpha thalassemia were described in literature. Clinical course ranged from moderate (non-transfusion dependent anemia) to severe (transfusion dependent thalassemia). In addition, one probable case of Hb barts hydrops fetalis was also reported in a Greek series. Hb Agrinio was first described in individuals of Greek or Cypriot origins. Subsequently, some cases were reported among patients living in Spain and Macedonia, most often of Gypsy origin. We report here the clinical presentation of the 8 homozygous cases diagnosed by molecular biology analysis in France and underline the severity of the antenatal phenotype of the disease. Methods: Cases were identified by contacting all the French laboratories involved in the molecular diagnosis of hereditary red blood cell (RBC) disorders. Three different families were retrieved, including 8 pediatric homozygous cases diagnosed by alpha globin gene sequencing between 2006 and 2020. Standardized clinical and laboratory data were obtained from treatment centers. All parents gave their written consent for molecular analysis and their authorization for participating in this study. Results: Consanguinity was present in all 3 families, however no obvious link was found between the 3. Two originated from Spain (1 of gypsy origin) and 1 from Bulgaria. All patients were homozygous for the HBA2: c.89T&amp;gt;C mutation, without any additional beta or alpha anomalies using gene sequencing and MLPA. Main clinical presentation findings of homozygous patients are reported in the table. Among the 8 cases, there was one in utero death at 22 weeks GA and 7 living births. Three patients, the more anemic at birth, died during the first hours of life with a clinical picture of hydrops fetalis for 2 of them. Despite a normal cerebral doppler at 32 weeks of GA, the third newborn (II2), presented at birth with a blueberry syndrome with cutaneous and hepatic extramedullary hematopoiesis, severe pulmonary arterial hypertension and Hb value of 6 g/dl, leading to neonatal death. Among the 4 survivor patients, one (III3), diagnosed in the antenatal period, benefited from in utero transfusions (TF) administered at 23 and 27 weeks because an accelerated middle cerebral artery peak systolic velocity of 52cm/s was measured. Hypospadias with ambiguous genitalia requiring surgical treatment was present in one patient and micropenis treated medically and undescended testis in a second one. All survivors (n=4/8) are currently under regular TF and chelation therapy. TF were generally (3/4) occasional in the first years of life and then became regular (&amp;gt;8 TF/year) later in childhood (at 6, 6, 7 years of age respectively). Conclusions: our national experience of homozygous Hb Agrinio cases revealed a more severe clinical course than reported in literature, with clinical presentation ranging from alpha-thalassemia major (Hb Barts hydrops fetalis) to severe non deletional HbH disease. Antenatal anemia was profound. In utero or neonatal deaths concerned half of the patients and additional ones were, even not biologically confirmed, also found in the family histories. Of note, congenital urogenital abnormalities similar to those found in the classical Hb Bart's Hydrops FetalisSyndrome were found in 2 patients. This up to now unreported severity could be explained by a closer monitoring and a more comprehensive clinical study of the cases/siblings allowing the antenatal period to be better described. The existence of aggravating genetic factor is another hypothesis and NGS analysis of genes involved in RBC disorders is planned. In couples at risk for homozygous Hb Agrinio, early genetic counseling and prenatal diagnosis should be offered. If the pregnancy is continued, a very close fetal ultrasound monitoring is mandatory and intrauterine TFs can be administered when severe fetal anemia is detected. Table Disclosures Thuret: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; Novartis pharma: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; bluebird bio, Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; Apopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Immunoadsorption, Intravenous Immunoglobulins and Rituximab (IIR): Successful New Treatment Approach for Severe Anti K- Alloimmunisation during Pregnancy

Background: Fetal red blood cells (RBC), erythroid and megakaryopoietic progenitor cells start to express the Kell (K) antigen already during the 10th gestational week (GW). Maternal anti-Kell alloimmunization (allo-anti-K-Ab) causes early (&amp;lt; 20th GW) and severe hemolytic disease of the fetus/newborn (HDFN) accompanied by erythroaplasia and potential thrombocytopenia. Therefore, prevention/delay of HDFN is highly relevant. Current treatment options include intra-uterine transfusions (IUT) of the fetus in case of suspected anemia, i.v. high-dose immunoglobulins (IVIG), plasma exchange and immunoadsorption (IA). Their efficacy often remains unsatisfactory and procedure related complications might occur. We present our new triple-treatment approach, combining IA + IVIG + Rituximab (Rtx) (IIR), which we successfully applied in 2 high-risk patients with allo-anti-K-Ab. Methods: The first patient was a 24 y, para 1, gravida 2, with an allo-anti-K-AB titer of 1:2000 in the 15th GW, at first presentation. Duplex-sonography showed no signs of fetal anemia. The second patient was a 40 y para 1, gravida 2. She presented with an allo-anti-K-Ab titer of 1:8000 in the 20th GW. Duplex-sonography revealed signs of severe anemia of fetus, requiring immediate IUT. Fetal K- genotyping (RT-PCR) using cell-free fetal DNA from maternal plasma confirmed a K- positive status in both fetuses. Duplex sonography monitoring was executed weekly, including the assessment of arteria cerebri media peak systolic velocity (ACM PSV). After having received informed consent of patients, we started the treatment at 14th and 21st GW in our first and second patient, respectively. IIR treatment cycles (1 cycle = 21 days) comprised 6x IA (each processing 2x the patient's plasma volume, weeks 1 + 2, every other day), followed by IVIG (1g/kg body weight) and i.v. Rtx (375 mg/m2) after the last IA of each cycle. This resulted in a total of 6 and 5 cycles for the first and second patient, respectively. We omitted Rtx for the last cycles in both patients. Results: IIR treatment resulted in a significant reduction of maternal anti K-titer to minimum of 1:32 in both patients, with a fluctuating course. In case 1 we performed a cordocentesis in the 30th GW because of an increased ACM PSV. The blood count of the fetus showed no anemia (Hb: 132 g/L) and only minimal Thrombocytopenia (145 G/L). The fetus in case 2 had already duplex- sonographic signs for a severe anemia at first presentation. Diagnostic cordocentesis confirmed a severe anemia (Hb 47 g/L) and also severe thrombocytopenia (21 G/L). Fetal alloimmune thrombocytopenia was ruled out. The first IUT of RBC has been performed right before starting IIR. Two weeks later a second IUT of RBC was necessary (fetal Hb 54 g/L), but thrombocytopenia was completely reversed (Tc: 352 G/l). The third and last IUT of RBC was performed 5 weeks later (Hb 99 g/L). Thereafter, no other signs of fetal anemia were detected. Patient one showed nausea/headache after her first IVIG-application and hypotonia/sinustachykardia during IA of the 5th cycle. IIR-treatment and IUT revealed no further adverse events. We continued treatment in both cases until the 32nd GW. Both neonates were born healthy in the 38th and 37th GW, respectively. The neonate in case 1 presented a mild anemia (Hb: 131 g/l), but normalized his Hb from 2nd day onwards. Both newborns showed a positive direct antiglobulin test (DAT), elution verified an anti-K-Ab, and their RBC were serologically positive for K. Both cases had normal Bilirubin and LDH levels, but a haptoglobin &amp;lt;0.1 g/l at birth. Both developed an icterus neonatorum during the first days after birth and needed phototherapy, Hb remained normal at all times. Flow cytometry of fetal lymphocytes showed a B-cell decrease (5.2%) in the first case and completely missing B-cells in the second case. Rtx level was low (2.13 µg/ml) in maternal plasma and neg. in the newborn of the first case. In the second case Rtx levels of the newborn and mother were 15,87 µg/ml and 4,5 µg/ml, respectively. In both cases, breastmilk showed no Rtx but positivity for anti-K-Ab (IgG). We observed no hemolysis of the newborns, while both were on breastfeeding. Conclusion: High-titer anti-Kell alloimmunisation causes early onset and severe HDFN and may be associated with severe thrombocytopenia. Treatment of affected pregnant women by using the Bern IIR-protocol was effective and safe in both severely affected patients. Disclosures Rovo: Novartis:Honoraria, Research Funding;CSL Behring:Research Funding;AG Alexion:Research Funding;Celgene:Honoraria, Other: financial support for congresses and conferences travel;BMS:Other: financial support for congresses and conferences travel;AstraZeneca:Other: financial support for congresses and conferences travel;Sanofi:Other: financial support for congresses and conferences travel;Amgen:Other: financial support for congresses and conferences travel;Roche:Other: financial support for congresses and conferences travel. OffLabel Disclosure: Rituximab is used for B-cell depletion in different malignant and non-malignant diseases. The off-label use concerns ist use in pregnant women with alloimmunisation.

Intrauterine Fetal Blood Transfusion (IUBT) for Rh Incompatibility – 12 Years’ Experience from Pakistan

To determine the perinatal outcome of pregnancies complicated by Rh-alloimmunisation, requiring intrauterine blood transfusion. Observational study. Feto-maternal Unit of Gene Tech Laboratory, Lahore, from 2007 to 2019. A retrospective analysis was done on the data of cases of intrauterine, intravascular blood transfusion given to at-risk foetuses to correct foetal anaemia due to Rh-alloimmunisation or parvovirus B19. All cases, who were eligible to receive IUBT were included in the study. Cases where historic data was not available have been excluded. A total of 305 intrauterine blood transfusion (IUBT) procedures were performed on 127 foetuses. The gestational age ranged from 18-32 weeks at the time of referral. Infra-hepatic part of umbilical vein was preferred for transfusion, but in some cases of anterior placenta, the cord insertion was approached with exception of only two cases where intra-cardiac route was employed. In this study, 71.6% of the babies survived, 14.2% were loss to follow and 14.2% died. IUBT is a safe procedure, especially when performed by experienced hands, and helps save the foetuses at risk. Mothers with Rh-alloimmunisation should be referred before developing hydrops fetalis for better outcome. Key Words: Red cell alloimmunisation, Intrauterine intravascular blood transfusion, Foetal anaemia.

Кровоток в средней мозговой артерии при тяжелых формах гемолитической болезни плода и многократных внутриутробных переливаниях крови

Кровоток в средней мозговой артерии при тяжелых формах гемолитической болезни плода и многократных внутриутробных переливаниях крови