Generation of human antibodies targeting human platelet antigen (HPA)-1a.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a condition during pregnancy, which can lead to thrombocytopenia and a bleeding tendency with intracranial hemorrhage (ICH) being the most concerning complication in the fetus or neonate. An incompatibility between human platelet antigen (HPA)-1a accounts for the majority of FNAIT cases. Binding of HPA-1a-specific alloantibodies to their target on fetal platelets and endothelial cells can induce apoptosis of megakaryocytes, disrupt platelet function, and impair angiogenesis. Currently, there is no screening program to identify pregnancies at risk for severe disease. A better understanding of HPA-1a-specific antibody heterogeneity in FNAIT could aid in identifying pathogenic antibody properties linked to severe disease. STUDY DESIGN AND METHODS: This study aimed to isolate HPA-1a-specific B-cells from an HPA-1a-alloimmunized pregnant woman. Using fluorescently labeled HPA-1a-positive platelets, single B-cells were sorted and cultured for 10 days to stimulate antibody production. Subsequently, supernatants were tested for the presence of antibodies by enzyme-linked immunosorbent assay and their reactivity towards HPA-1a-positive platelets. Amplification and sequencing of variable regions allowed the generation of monoclonal antibodies using a HEK-Freestyle-based expression system. RESULTS: Three platelet-specific B-cells were obtained and cloned of which two were specific for HPA-1a, named D- and M-204, while the third was specific for HLA class I, which was named L-204. DISCUSSION: This study outlined an effective method for the isolation of HPA-1a-specific B-cells and the generation of monoclonal antibodies. Further characterization of these antibodies holds promise for better understanding the pathogenic nature of alloantibodies in FNAIT.

Frequency of human platelet antigens (HPA) in the Greek population as deduced from the first registry of HPA-typed blood donors.

BACKGROUND AND OBJECTIVES: Human platelet antigens (HPA) play a central role in foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura and some cases of platelet therapy refractoriness. The frequency distribution of HPA had not been studied in the Greek population before we started to create a registry of HPA-typed apheresis platelet donors. The aim of this study was the determination of the frequency of various HPA in the Greek population, through the establishment of a registry of typed donors. MATERIALS AND METHODS: Here, we report on the first 1000 platelet donors of Greek origin who gave informed consent and were genotyped for 12 pairs of antithetical HPA by Single Specific Primer-Polymerase Chain Reaction (SSP-PCR), including HPA-1, HPA-3, HPA-5 and HPA-15. Antigen frequencies are reported, and allele frequencies were calculated and compared with other European and non-European populations. Tested donors cover all ABO and Rhesus D antigen spectrum. RESULTS: Antigen and allele frequencies are very similar to other White populations. The frequency of HPA-1bb is 2.9% in our study, and the frequency of HPA-2b, HPA-4b, HPA-9b and HPA-15b is also slightly higher than in other literature reports, while the frequency of HPA-15b was found higher than that of HPA-15a. CONCLUSION: We report antigen and allele frequencies for a large array of clinically significant HPA for the first time in the Greek population. Frequencies are consistent with other European populations. This registry of HPA-typed platelet donors, available to donate on demand, is an important asset for the treatment of FNAIT cases in Greece.

Does anti-HPA-1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) ensues from parental incompatibility for platelet alloantigens with maternal sensitization. HPA-1a/1b incompatibility is the most common cause of FNAIT in Caucasians. Placental villitis and lower birthweight in FNAIT suggest anti-HPA-1a may have effects beyond inducing thrombocytopenia. OBJECTIVES: Does FNAIT secondary to anti-HPA-1a result in smaller newborns and, the corollary, does antenatal management of FNAIT increase birthweight? STUDY DESIGN: Birthweights of 270 FNAIT-affected newborns from a randomized clinical trial and a NAITbabies.org survey (135 paired siblings) were compared with those of published controls and treated to untreated FNAIT-affected siblings. Birthweights were converted to percentiles to account for gestational age, sex, and role of birth order in birth weight. Body weights of FNAIT-affected and -unaffected pups in a mouse FNAIT model were analyzed. RESULTS: Untreated siblings in both the clinical trial and NAITbabies.org cohorts were not small, compared with normal controls. However, treated siblings in both cohorts had significantly higher birthweight percentiles compared with their previous untreated affected sibling. After accounting for gestational age, sex, and birth order, increased birthweight percentile in treated compared with the untreated siblings remained significant in both cohorts. FNAIT-affected neonatal mice had lower bodyweights than FNAIT-unaffected pups. CONCLUSIONS: Untreated FNAIT-affected newborns were not small; however, treatment of FNAIT-affected pregnancies increased newborn birthweights despite corrections to account for other factors that might have influenced the results. High dose IVIG is believed to "block" FcRn and lower maternal anti-HPA-1a levels, and thus increase birthweights by reducing levels of maternal anti-HPA-1a and reducing placental villitis.

HLA antibodies in fetal and neonatal alloimmune thrombocytopenia.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive. This study sought to examine whether clinically suspected FNAIT cases with absent maternal HPA antibodies had different HLA antibody strength and specificity compared to controls. STUDY DESIGN AND METHODS: A retrospective case-control study assessed class I HLA antibody strength and specificity in cases submitted for testing to Versiti, Wisconsin. There were 813 cases that met initial screening criteria, but written consent could only be obtained for 50. After review of medical records and expert panel review, 31 cases with clinical criteria of FNAIT and maternal HLA but not HPA antibodies were included. Each case was matched for maternal age, gestational age at delivery, parity, and race/ethnicity to two controls from unaffected pregnancies that had maternal serum HLA antibodies. RESULTS: FNAIT cases were found to have both significantly higher HLA antibody strength, measured by mean fluorescence index (MFI), and broader HLA antibody specificity at antigen epitope level, compared to matched controls (p < .001). p-values remained significant after controlling for parity and gestational age at delivery. DISCUSSION: Additional studies are needed to further examine whether the strong HLA antibodies identified in HPA-antibody-negative cases directly cause neonatal thrombocytopenia and whether prenatal treatment may be warranted in select cases to prevent recurrence.

Clinical and laboratory predictors of fetal and neonatal alloimmune thrombocytopenia.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of intracranial hemorrhage (ICH) in thrombocytopenic term infants. We investigated clinical and laboratory predictors of severe FNAIT in a tertiary care referral center. STUDY DESIGN AND METHODS: Retrospective cohort study over a 30-year period. We defined FNAIT as recurrence of neonatal thrombocytopenia in a subsequent pregnancy; and severe outcomes as any of: (1) a birth platelet count below 20 × 109 /L; (2) ICH or (3) fetal death. We used a generalized estimating equations analysis and classification tree analysis to identify risk factors for severe FNAIT in a subsequent pregnancy. RESULTS: During index pregnancies (n = 135 in 131 mothers), 71 infants (52.6%) had severe outcomes including a platelet count <20 × 109 /L (n = 45), fetal or neonatal ICH (n = 32), or fetal death (n = 4). During subsequent pregnancies (n = 72), 15 infants (20.8%) had severe outcomes including birth platelets <20 × 109 /L (n = 10), ICH (n = 2), or death (n = 3). Forty-two women (58.3%) received antenatal intravenous immune globulin (IVIG) during subsequent pregnancies. Eight mothers (n = 9 infants) had severe FNAIT outcomes despite receiving antenatal IVIG. Maternal antibodies to human platelet antigens (HPA) was the only independent predictor of severe FNAIT in a subsequent pregnancy (OR = 25.3, p = .004). Nevertheless, one of 43 infants from antibody-negative mothers had a severe outcome. CONCLUSIONS: The presence of anti-HPA is highly indicative of the diagnosis of severe FNAIT; however, we observed one infant who had severe FNAIT recurrence, defined using strict clinical criteria, without a maternal antibody. Improved diagnostic and therapeutic strategies are needed to prevent severe FNAIT in high-risk mothers.

Preliminary mechanism in fetal alloimmune thrombocytopenia associated with anti-HPA 15b antibodies.

OBJECTIVE: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disease that can cause fetal hydrops, a rare but life-threatening condition in which abnormal amounts of fluid accumulate in one or two areas of the fetus's body. A case of FNAIT with fetal hydrops caused by anti-HPA-15b antibodies was involved in this study, as we investigated whether or not anti-HPA-15b antibodies can induce endothelial angiogenesis and apoptosis. METHODS: The monoclonal antibody immobilization of platelet antigens assay (MAIPA) was used to identify anti-HPA-15b antibodies. The three groups in Tube formation and apoptosis assays were the PBS group, the AB serum IgG group, and the anti-HPA-15b serum IgG group, all reacted with HPA-15bb HUVEC. RESULTS: The presence of anti-HPA-15b antibodies was found in this case by MAIPA assay. The OD values are 0.33 and 0.21, reacted with HPA-15bb and HPA-15ab platelets, respectively (cutoff OD value = 0.2). Quantitative analysis revealed that the length of capillary-like tube induced by anti-HPA-15b antibodies was significantly decreased over that of AB serum IgG (*p = 0.0005), but weaker than when incubated with thrombin (**p = 0.0009). The apoptosis results show a significantly increased number of apoptotic endothelial cells in the anti-HPA-15b antibody IgG group when compared with the PBS and AB serum IgG groups (*p < 0.0001, **p < 0.0001). In addition, there is no statistical difference between the PBS and AB serum groups. CONCLUSION: Anti-HPA-15b antibodies can inhibit angiogenesis and induce apoptosis. This may associate with hydrops fetalis (HF), or fetal hydrops of FNAIT.

Characterization of glycoprotein IIb/IIIa-specific alloantibodies induced by cross-strain platelet immunization in mice.

BACKGROUND: We previously described a mouse model in which platelet immunization between selected strains leads to production of alloantibodies and severe autoimmune thrombocytopenia and mimics the human condition posttransfusion purpura (PTP). This report describes studies defining epitopes recognized by these alloantibodies. STUDY DESIGN: Hybridomas were produced from spleen cells of immunized mice. Glycoprotein (GP) targets of resulting monoclonal antibodies were characterized by immunoprecipitation using platelets from the immunizing strains. Antigens defined by single amino acid (AA) polymorphisms recognized by monoclonal antibodies were identified by mutagenizing target glycoproteins expressed in Chinese hamster ovary cells and observing the effects on antibody binding. RESULTS: Three monoclonal antibodies (417.1, 417.3, 425.1) were produced that recognized GPIIb on immunizing platelets. Monoclonal antibodies 417.1 and 417.3 both required G111 and 425.1 required V37, located on the beta propeller domain of GPIIb, for binding to platelets from the immunizing strains C57 and PWK, respectively. Injection of 417.3 and 425.1 into mice caused platelet destruction only in mice with GPIIb containing the targeted AAs. CONCLUSIONS: Findings made provide evidence that alloantibodies produced by mice experiencing thrombocytopenia in a mouse model of PTP are specific for single AA polymorphisms that differ in GPIIb/IIIa integrin of the immunizing and immunized strains and therefore closely resemble the potent alloantibodies found in patients with PTP. The observations show that naturally occurring single AA differences in GPIIb/IIIa integrin of various mouse strains are highly immunogenic in the mouse strains studied and readily induce antibodies comparable to human platelet antigen-specific antibodies found in transfused and pregnant humans.

Platelet CD36 deficiency is present in 2.6% of Arabian individuals and can cause NAIT and platelet refractoriness.

BACKGROUND: CD36 isoantibodies are capable of inducing neonatal alloimmune thrombocytopenia (NAIT) and platelet refractoriness. As to now the CD36 type I deficiency has been reported in East Asian and African individuals. However, it is virtually unknown in Caucasians. The aim of this study was to display the prevalence of the CD36 deficiency within parts of the Arabian population in Germany. Secondly, we are presenting the case of a newborn suffering from NAIT which was induced by CD36 antibody. METHODS: Platelet (p) CD36 was determined by flow cytometry on 1328 samples mainly from individuals of Arabian origin and a family with a neonate affected by NAIT. DNA sequencing was performed on all pCD36-negative samples. RESULTS: Thirty-five (2.64%) of all donor samples were pCD36 negative, 19 (1.43%) had a weak expression. Including only individuals from the Arabian peninsula, frequencies were 3.39% and 1.75%, respectively. CD36 type I deficiency on both platelets and monocytes combined with a CD36 isoantibody were detected in the mother of the NAIT baby. The baby was successfully transfused with two HPA-unselected platelet concentrates. In case of need, two platelet units with a weak pCD36 expression were on hand. A total of 45 different CD36 mutations were detected within pCD36-negative individuals, some being homozygous, most of them only present on one allele. CONCLUSION: The CD36-negative phenotype is present in a significant number of individuals of Arabian origin and enables CD36 isoimmunization in NAIT or refractoriness. Blood transfusion services should be aware of such cases.

New developments in fetal and neonatal alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia, the platelet equivalent of hemolytic disease of the fetus and newborn, can have devastating effects on both the fetus and neonate. Current management of fetal and neonatal alloimmune thrombocytopenia in a subsequent affected pregnancy involves antenatal administration of intravenous immune globulin and prednisone to the pregnant woman to prevent the development of severe fetal thrombocytopenia and secondary intracranial hemorrhage in utero. That therapy has proven to be highly effective but is associated with maternal side effects and is expensive. This commentary describes 4 advances that could substantially change the current approach to detecting and managing fetal and neonatal alloimmune thrombocytopenia in the near future. The first would be an introduction of a program to screen all antepartum patients in this country for pregnancies at risk of developing fetal and neonatal alloimmune thrombocytopenia. Strategies to implement this complex process have been described. A second advance is testing of cell-free fetal DNA obtained from maternal blood to noninvasively determine the fetal human platelet antigen 1 genotype. A third, in preliminary development, is creation of a prophylactic product that would be the platelet equivalent of Rh immune globulin (RhoGAM). Finally, a fourth major potential advance is the development of neonatal Fc receptor inhibitors to replace the current medical therapy administered to pregnant women with an affected fetus. Neonatal Fc receptor recycles plasma immunoglobulin G to increase its half-life and is the means by which immunoglobulin G crosses the placenta from the maternal to the fetal circulation. Blocking the neonatal Fc receptor is an ideal way to prevent maternal immunoglobulin G antibody from causing fetal and neonatal alloimmune thrombocytopenia in a fetus at risk of developing that disorder. The pertinent pathophysiology and rationale for each of these developments will be presented in addition to our thoughts relating to steps that must be taken and difficulties that each approach would face for them to be successfully implemented.

The prevalence of HPA-1a alloimmunization and the potential risk of FNAIT depend on both the DRB3*01:01 allele and associated DR-DQ haplotypes.

Alloimmunization against human platelet antigen (HPA)-1a during pregnancy can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) and severe bleeding in the foetus or newborn and likely depends on several factors. HPA-1a alloimmunization is associated with DRB3*01:01, which is associated with several DR-DQ haplotypes. However, it is not known to what extent these haplotypes contribute to the prevalence of HPA-1a alloimmunization. HPA-1a-alloimmunized women, identified in a prospective study, and random donors were typed for selected DRB3, DRB4, DRB1, DQA1 and DQB1 alleles to determine allele and DR-DQ haplotype frequencies. DRB3*01:01 was carried by 94% HPA-1a-immunized women compared to 27% in the general population. In the first population, the DR3-DQ2 haplotype was overrepresented (P < .003). The prevalence of HPA-1a alloimmunization was estimated to be about twice as frequent with DR3-DQ2 compared to DR13-DQ6, together accounting for about 90% of DRB3*01:01-positive individuals. Further, we examined DQB1*02 and DRB4*01:01 alleles for their reported association with HPA-1a alloimmunization, in the context of DR-DQ haplotypes. Since ~ 80% of DQB1*02 alleles are linked to the DR3-DQ2 haplotype, the association might be coincidental. However, the DQB1*02:02-associated DR7-DQ2 haplotype was also overrepresented in alloimmunized women, suggesting a role for this allele or haplotype in HPA-1a alloimmunization. As DRB4*01:01 is predominantly associated with the DR7-DQ2 haplotype in HPA-1a-alloimmunized individuals, the reported association with FNAIT may be coincidental. Typing for DR-DQ haplotypes revealed important genetic associations with HPA-1a alloimmunization not evident from typing individual alleles, and the presence of different DRB3-associated DR-DQ haplotypes showed different prevalence of HPA-1a alloimmunization.

Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia.

Anti-HPA-1a-antibodies are the main cause of fetal and neonatal alloimmune thrombocytopenia (FNAIT) which may result in intracranial hemorrhage (ICH) and death among fetuses and newborns. Advances in understanding the pathogenesis of FNAIT and proof of concept for prophylaxis to prevent immunization suggest that development of hyperimmune anti-HPA-1a IgG aimed at preventing immunization against HPA-1a and FNAIT is feasible. Anti-HPA-1a IgG can be obtained either by isolating immunoglobulin from already-immunized women or by development of monoclonal anti-HPA-1a antibodies. Here we discuss recent advances that may lead to the development of a prenatal and postnatal prophylactic treatment for the prevention of HPA-1a-associated FNAIT and life-threatening FNAIT-induced complications.

The use of IVIg in fetal and neonatal alloimmune thrombocytopenia- Principles and mechanisms.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare neonatal disorder that is caused by alloimmunization against platelet antigens during pregnancy. Although rare, affecting only 1 in 1000 live births, it can cause intracranial hemorrhage and other bleeding complications that can lead to miscarriage, stillbirth and life-long neurological complications. One of the gold-standard therapies for at risk pregnancies is the administration of IVIg. Although IVIg has been used in a variety of different disorders for over 40 years, its exact mechanism of action is still unknown. In FNAIT, the majority of its therapeutic effect is thought the be mediated through the neonatal Fc receptor, however other mechanisms cannot be excluded. Due to safety, supply and other concerns that are associated with IVIg use, alternative therapies that could replace IVIg are additionally being investigated. This includes the possibility of a prophylaxis regimen for FNAIT, similarly to what has been successfully used in hemolytic disease of the fetus and newborn for over 50 years.

Murine models for studying treatment, prevention and pathogenesis of FNAIT.

Maternal alloimmunization to paternally inherited antigens on fetal/neonatal platelets can cause fetal/neonatal alloimmune thrombocytopenia (FNAIT) after antibody-mediated removal of platelets from the fetal circulation. The complications vary from mild bleeding symptoms to severe intracranial hemorrhage and subsequent neurological impairment or death. Studies on in vivo mechanisms are challenging to measure directly in pregnant women, rendering murine models as valuable and attractive alternatives, despite some critical differences between mice and men affecting the translational value. Here we present and discuss, the different murine models that substantially have increased our knowledge and understanding of FNAIT pathogenesis - as well as pre-clinical evaluation of therapeutic and preventive strategies.

Prospects for risk stratification of anti-HPA-1a alloimmunized pregnant women.

A diagnosis of fetal/neonatal alloimmune thrombocytopenia (FNAIT) is made if a platelet-specific antibody is detected in the mother and the fetus or newborn carries the cognate antigen. Some children will experience very low platelet counts or even intracranial hemorrhage with devastating consequences, whereas others are largely unaffected. At the moment, predictive tools to forecast the severity of FNAIT during pregnancy are not available and over- or under-treatment may put the mother or the fetus at risk. A number of potential modulators of FNAIT severity have been reported. Maternal immune responses differ in respect to the IgG subtype composition, the glycosylation pattern of the antibodies, their fine specificity, and their functional effects on platelets, the trophoblast, and endothelial cells. In addition, antibody levels are variable. The efficacy of IgG transfer and, on the fetal side, gender and inflammatory responses, were also investigated for their potential impact on FNAIT severity. These potential risk modulators are scrutinized for available experimental and clinical evidence. Antibody glycosylation and anti-endothelial activity are hot candidates which, most likely in conjunction with the antibody level, should be explored further as tools to stratify fetal risk.

Progress and development of platelet antibody detection.

Human platelet antibody (HPA) detection is necessary for the diagnosis and therapeutic decisions for refractoriness to platelet transfusions, post transfusion purpura and fetal and neonatal alloimmune thrombocytopenia. In the last four to five decades many new developments, both in knowledge and methods, have increased the quality of platelet serology. However, the quest for the optimal antibody detection method(s) encountered, sometimes unexpected, difficulties. In this review the various aspects concerning platelet antibody test methods and detection of platelet antibodies both for the diagnostic and screening setting are discussed.

Hydrops fetalis associated with anti-CD36 antibodies in fetal and neonatal alloimmune thrombocytopenia: Possible underlying mechanism.

OBJECTIVES: In the present study, we asked whether anti-CD36 antibodies impair the maturation of erythropoietic stem cells to mature red blood cells (RBCs), leading to anaemia and hydrops fetalis (HF). BACKGROUND: Recent studies have shown the importance of anti-CD36 antibodies in the development of Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT). In comparison to other types of antibody-mediated FNAIT, anti-CD36 antibodies are frequently associated with anaemia and HF. As mature RBCs do not express CD36, the reason for this phenomenon is currently not fully understood. MATERIAL AND METHODS: A case of FNAIT with signs of HF was characterised in this study. Maternal anti-CD36 antibodies were isolated by an absorption/elution approach. We cultured haematopoietic stem cells (HSCs) with purified anti-CD36 antibodies, and the formation of burst-forming unit-erythroid and colony-forming unit-erythroid (CFU-E/BFU-E) cells was analysed. Apoptosis of HSCs was also investigated. RESULTS: Analysis of the mother showed type-1 CD36 deficiency. Anti-CD36 antibodies were found in maternal serum, as well as on fetal platelets, by ELISA, and the specificity of these antibodies was further substantiated by flow cytometry. In comparison to control IgG, incubation of HSCs with purified anti-CD36 antibodies led to a significant reduction in CFU-E/BFU-E cell formation, and this result was associated with an increased number of apoptotic CD34+ erythroid/myeloid precursor cells. Administration of intra-uterine transfusion with washed RBCs was effective in improving fetal anaemia. CONCLUSIONS: Anti-CD36 antibodies may cause anaemia and trigger HF through apoptosis of CD34+ erythroid/myeloid precursor cells. However, the contribution of other cells must also be taken into account.

Non-invasive risk-assessment and bleeding prophylaxis with IVIG in pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia: management to minimize adverse events.

INTRODUCTION: In pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT), prenatal intervention in subsequent pregnancies may be required to prevent fetal bleeding. Several invasive and non-invasive protocols have been published: amniocentesis for fetal genotyping, fetal blood sampling for the determination of fetal platelet count, intrauterine platelet transfusions, and weekly maternal i.v. immunoglobulin (IVIG) infusion with or without additional corticosteroid therapy. This is the first retrospective study that report the experience with a non-invasive protocol focused on side effects of maternal IVIG treatment and neonatal outcome. METHODS: Pregnant women with proven FNAIT in history and an antigen positive fetus were treated with IVIG (1 g/kg/bw) every week. To identify potential IVIG-related hemolytic reactions isoagglutinin titer of each IVIG lot and maternal blood count were controlled. IVIG-related side effects were prospectively documented and evaluated. Furthermore, ultrasound examination of the fetus was performed before starting IVIG administration and continued regularly during treatment. Outcome of the index and subsequent pregnancy was compared. Corresponding data of the newborns were analyzed simultaneously. RESULTS: IVIG was started at 20 weeks of gestation (median). Compared to the index pregnancy, platelet counts of the newborns were higher in all cases. No intracranial hemorrhage occurred (Index pregnancies: 1 case). Platelet counts were 187 × 109/l (median, range 22-239, 95% CI) and one newborn had mild bleeding. No severe hemolytic reaction was observed and side effects were moderate. CONCLUSION: Among pregnant women with FNAIT history, the use of non-invasive fetal risk determination and maternal IVIG resulted in favorite outcome of all newborns. Invasive diagnostic or therapeutic procedures in women with a history of FNAIT should be abandoned.

Management and Neonatal Outcomes of Pregnancies with Fetal/Neonatal Alloimmune Thrombocytopenia: A Single-Center Retrospective Cohort Study.

BACKGROUND: There is no consensus regarding the optimal antenatal treatment of fetal/neonatal alloimmune thrombocytopenia (F/NAIT). We aimed to review the fetal blood sampling (FBS)-related risk, fetal response to maternal intravenous immunoglobulin (IVIG), and cesarean section (CS) rate in pregnancies with a history of F/NAIT. METHODS: Maternal demographics, alloantibodies, pregnancy management, fetal and neonatal outcomes, and index case characteristics were collected. Responders (R) and non-responders (NR) were defined as women treated with IVIG in whom fetal platelets (PLTs) were normal or low (< 50 × 109/L). RESULTS: An FBS-related risk occurred in 1.6% (2/119) of procedures. Maternal characteristics did not differ between responders (n = 21) and non-responders (n = 21). HPA-1a antibody was detected in all non-responders and in 72% of responders (p < 0.01). The index case had a significantly lower PLT count at birth in non-responders versus responders (median PLT count: R = 20 × 109/L [IQR 8-43] vs. NR = 9 × 109/L [IQR 4-18], p < 0.02). No differences were found in IVIG treatment duration or dosage. PLTs at birth were significantly lower in non-responders compared to responders. No intracranial hemorrhages occurred. CSs were performed for obstetric indications only in all but two cases. CONCLUSION: Maternal IVIG can elicit different fetal responses. The lack of prognostic factors to predict responders or non-responders suggests that there remains a role for FBS in F/NAIT in experienced hands.

Fetal and neonatal alloimmune thrombocytopenia.

OBJECTIVE: This article shows our experience with fetal and neonatal alloimmune thrombocytopenia (FNAIT) on a particular patient and the difficulties we faced during the hospitalization. DESIGN: Case report. SETTING: Department of Obsterics and Gynecology 1st Faculty of Medicine, Charles University and General Faculty Hospital in Prague. METHODS: Our experience with FNAIT therapy. RESULTS: According to literature is recommended to use IVIG for FNAIT treatment. Women, who were treated by IVIG have better results, in comparison with women, who had no treatment at all. Our case is not confirming this statement, because first pregnancy of our patient terminated by IUFD, on the other hand second pregnancy was successful and she delivered healthy child. CONCLUSION: FNAIT is relatively rare disease, but if it appears, it can be dangerous for a fetus or for a new-born baby. In the worst case FNAIT can result in intracranial bleeding or prenatal death. There are limited preventive steps and available therapy produces uncertain results. The only partially accepted treatment substance is IVIG (intravenous immunoglobulins). Unfortunately, this therapy is very expensive and not accepted by some experts. This article shows our experience with FNAIT on a particular patient and the difficulties we faced during the hospitalization.

Imaging and management of fetuses and neonates with alloimmune thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the most common cause of severe neonatal thrombocytopenia and intracranial bleeding in term newborns. Intracranial hemorrhage (ICH) commonly results in death or severe, lasting neurologic disability. The timing of ICH is also important for management of the next affected pregnancy in cases of FNAIT. This manuscript reviews the advantages and disadvantages of the different radiologic methodologies to identify and characterize ICH. It discusses the limits of ultrasound and the advantages of magnetic resonance imaging allowing avoidance of the radiation associated with computed tomography (CT) scans.