Severe Neonatal Alloimmune Thrombocytopenia Research Articles

Neonatal alloimmune thrombocytopenia due to anti-HPA 5a in a HPA-5a homozygous neonate

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Cases of FNAIT caused by HPA-5a antigen are extremely rare, and usually not severe. We report a case of FNAIT caused by anti-HPA antibodies directed to the HPA-5a antigen. The thrombocytopenia was moderate with a minimal platelet count of 36 × 109/L by day 3, and spontaneously resolved by day 10.The pregnancy had been obtained by in vitro fertilization using embryo donation, creating a complete genetic disparity between the HPA 5b5b mother and the HPA 5a5a homozygous neonate.The use of ART with gamete donation can increase the risk and the severity of alloimmune thrombocytopenia and must be considered in new and subsequent pregnancies.

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Severe neonatal alloimmune thrombocytopenia caused by maternal sensitization against a new low-frequency alloantigen (Domb ) located on platelet glycoprotein IIIa.

Severe neonatal alloimmune thrombocytopenia caused by maternal sensitization against a new low-frequency alloantigen (Domb ) located on platelet glycoprotein IIIa.

Fatal alloimmune thrombocytopenia due to anti-HLA alloimmunization in a twin pregnancy: A very infrequent complication of assisted reproduction

The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Platelets express the HLA-A and B antigens on their membrane and some studies report that maternal anti-HLA class I antibody can also cause FNAIT. We report here a very unusual case of a first twin pregnancy produced in vitro by oocyte and semen donation where the mother developed markedly elevated HLA antibodies, in the absence of anti-platelet or anti-neutrophil antibodies, that provoked in one of the twins a profound thrombocytopenia and intracranial hemorrhage and a mild thrombocytopenia and neutropenia in the second twin lasting until the fourth month of life. In addition, anti-D alloimmunization provoked hemolytic disease of the newborn with intrauterus anemia detected in the first twin and post-natal anemia in the second twin that required red blood cell transfusion and phototherapy. We hypothesize that the complete HLA-incompatible twin pregnancy due to the oocyte donation might have contributed to the severity of the clinical manifestations.

Management of infants born with severe neonatal alloimmune thrombocytopenia: the role of platelet transfusions and intravenous immunoglobulin

Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal incompatibility most commonly induced by maternal anti-HPA-1a alloantibodies. Transfusion of immunologically compatible platelets (PLTs) to prevent cerebral hemorrhage, the most severe complication in affected newborns, is usually recommended. Such PLT concentrates, however, are often not readily available. The efficacy of random-donor PLT transfusions and intravenous immunoglobulin (IVIG) for the management of 17 neonates across four centers with unexpected, severe NAIT was evaluated. Neonates were treated with random-donor PLTs alone (n=7), random-donor PLTs with IVIG (n=8), or matched HPA-1bb PLTs (n=2). All but one patient (treated with random PLTs and IVIG) achieved a posttransfusion PLT count of higher than 30 × 10(9) /L after the first PLT transfusion. The PLT count remained higher than 30 × 10(9) /L for longer than 24 hours in five of seven, seven of eight, and two of four newborns who received random-donor PLTs alone, random-donor PLTs with IVIG, or matched HPA-1bb PLTs, respectively. None of the newborns developed major bleeding or intracranial hemorrhage. IVIG did not appear to improve either posttransfusion PLT counts or total PLT transfusion requirements. Transfusion of random-donor PLTs alone was effective at correcting critically low PLT counts and should be considered as first-line treatment of newborns with unexpected severe NAIT.

The implementation of surface plasmon resonance technique in monitoring pregnancies with expected fetal and neonatal alloimmune thrombocytopenia

Maternal anti-HPA-1a alloantibodies are responsible for most cases of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT). The presence of HPA-1a alloantibodies in maternal blood alone does not predict the fetal platelet (PLT) count, and the predictivity of antibody titers determined by enzyme immunoassays (EIAs) is debated. In contrast to EIA, surface plasmon resonance (SPR) provides information on antibody-binding properties. Sequential sera from pregnant women with expected FNAIT were assessed for HPA-1a alloantibodies using SPR. Group I (n = 6) was treated with intravenous immunoglobulin (IVIG) and steroids beginning at 19 weeks of gestation (w.g.), and Group II (n = 4) received intrauterine PLT transfusions (IUT) beginning at 22 w.g. Maternal alloantibodies were quantified using an HPA-1a monoclonal antibody (MoAb) as a standard. Antibody avidity was determined as the ratio of B700 (end of the dissociation phase) to B350 (end of the association phase); the area under the curve (AUC) was calculated to determine overall antibody binding. After 22 w.g., alloantibody characteristics remained stable in both groups, while there was a steep decrease in B700 and B350 values between 16 and 22 w.g. (assessed only in Group I), indicating a decrease in anti-HPA-1a alloantibody concentrations. Interestingly, the AUCs of the last maternal sample before elective delivery appeared to be correlated with fetal and neonatal PLT counts (p = 0.014 and 0.017, respectively). SPR provides quantitative information on HPA-1a alloantibody characteristics in addition to monoclonal antibody-specific immobilization of platelet antigens. SPR results can be calibrated using a MoAb standard and should be further assessed for a potential correlation with fetal PLT count.

The human platelet antigen‐21bw is relatively common among Asians and is a potential trigger for neonatal alloimmune thrombocytopenia

We and others have identified more than 20 low-frequency human platelet (PLT) antigens (HPAs) that can induce antibodies capable of causing neonatal alloimmune thrombocytopenia (NAIT).1–4 Like HPA-1a and HPA-4b, the antigens that most often trigger NAIT in Caucasian and Asian populations, respectively, the incidence of low-frequency antigens is likely to vary significantly in different ethnic and racial populations. We recently described HPA-21bw, a low-frequency antigen, responsible for a single case of severe NAIT in a presumed Caucasian family.1 The HPA-21bw antigen results from a G>A1960 mutation (RS70940817), in ITGB3, encoding PLT glycoprotein (GP) β3 subunit (GPIIIa) and creates a Glu>Lys substitution at Residue 628 in mature β3. No examples of HPA-21bw were identified in 100 unrelated Caucasian individuals.1 We recently encountered a second case of NAIT apparently caused by HPA-21bw in an Asian family (unpublished). The mutation encoding HPA-21bw was also identified in two of 38 Asian individuals tested in a hypertension and insulin resistance study according to the human SNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; ss95216694). These observations suggested that HPA-21bw, like HPA-4b, might be more prevalent in Asian than in Caucasian populations and therefore a more common trigger for NAIT. To examine this possibility, we determined the gene frequency of the mutation encoding HPA-21bw in anonymized DNA samples identified by age, sex, and self-declared race/ethnicity obtained from the Retrovirus Epidemiology Donor Study (REDS) General Serum Repository of the National Heart, Lung, and Blood Institute (NHLBI) made available by the NHLBI Biologic Specimen and Data Repository guardian (BioLINCC). These specimens were collected from blood donors at five locations in the United States (Baltimore, Detroit, Los Angeles, Oklahoma City, and San Francisco) between December 1994 and December 1995. Anonymized samples were also obtained from Caucasian blood donors at BloodCenter of Wisconsin. Genotyping for HPA-21bw was performed with an allelic discrimination assay using PerfeCTa qPCR SuperMix, UNG, Low ROX (Quanta Biosciences, Gaithersburg, MD).2 Results are summarized in Table 1. No examples of HPA-21bw were found in 1110 unrelated Caucasians, 611 African Americans, or 252 Hispanic blood donors. However, 6 of 531 Asians donors were HPA-21a/bw (prevalence, 1.1%; gene frequency, 0.0056). TABLE 1 Frequency analysis of HPA-21bw in various populations We used the exact binomial methods for statistical inference: Clopper-Pearson confidence intervals (CIs) and Fisher’s exact test. The prevalence of HPA-21bw among Asians, estimated as 1.1% (95% CI, 0.4%–2.4%) is significantly greater than in Caucasians (p = 0.001) and African Americans (p = 0.01). The comparison with Hispanics is not significant (p = 0.18); however, the sample size is too small for this comparison. Based on one-sided CIs we are 95% confident that the prevalence of HPA-21bw among Caucasians is less than 0.3%, among African Americans less than 0.5%, and among Hispanics less than 1.2%. To date the HPA-4b (Penb) polymorphism in GPIIIa is the most common trigger for antibodies that cause NAIT in the Asian population. Having an allelic frequency of 0.0045, HPA-4b is expressed in approximately 1% of the Asian population.5 In contrast HPA-6bw in GPIIIa, though found in 2.7% of the Asian population,5 is not a common trigger of NAIT. Taking into consideration that HPA-21bw is known to initiate severe NAIT,1 has already been implicated as the trigger for NAIT in one Asian family (unpublished), and has an allelic frequency of 0.2% to 2.2% (95% confidence limits) in the Asian population, routine typing for this antigen in cases of suspected NAIT involving Asian families appears indicated.

Fetal Intracerebral Mass With Major Perinatal Implications

A 27-year-old G3A2L0 woman is referred to the Maternal Fetal Medicine clinic after a routine third-trimester ultrasound in a community setting shows an intracerebral mass at 30 weeks’ gestational age (GA). The mother is healthy other than being a chronic carrier of hepatitis B. She is blood type B positive with a negative antibody screen. She previously had two first-trimester therapeutic abortions, and this is her first pregnancy with her current partner. The pregnancy was uneventful with a negative integrated prenatal screen and ultrasounds with normal results at 14 and 20 weeks’ GA. Mild maternal thrombocytopenia was detected throughout the pregnancy (lowest platelet count 97 × 109/L) with reported increased bruising. There is no family history of bleeding disorders in either her or her partner's family. The findings on physical examination are normal with no signs of bleeding, bruising, or petechiae. A complete blood cell count shows a hemoglobin level of 11.3 g/dL (113 g/L) and a platelet count of 124 × 103/μL (124 × 109/L). A repeat ultrasound confirms a large complex intracerebral mass with hypoechoic areas suggestive of cysts as well as echogenic portions that were felt to be either solid or to represent bleeding with clots. The composition of the mass is clarified by maternal MRI at 31 weeks’ GA, which shows a large cystic complex lesion measuring 5.0 × 3.8 × 4.5 cm (Fig 1). There is a solid component that shows blooming on the susceptibility-weighted imaging sequence, suggestive of blood products, clot, or calcification, but an underlying neoplastic process or vascular anomaly cannot be excluded. Figure 1. MRI of the maternal pelvis at 31 weeks’ GA without gadolinium. Large complex cystic lesion (arrow) in the frontoparietal region of the left cerebral hemisphere of the fetus with characteristics suggestive of blood products. …

The first two cases of neonatal alloimmune thrombocytopenia associated with the low‐frequency platelet antigen HPA‐21bw (Nos) in Japan

Neonatal alloimmune thrombocytopenia (NAIT) is a disorder characterized by maternal alloimmunization against paternal fetal platelet antigens. Two healthy, unrelated Japanese women each gave birth to a child with severe NAIT. To elucidate the maternal causes of NAIT, we conducted serologic and genetic studies in these two NAIT infants. The serologic experiments localized the antigens to the glycoprotein (GP) IIIa subunit of the GPIIb/IIIa complex. Sequence-based typing studies subsequently identified a G>A mutation at Nucleotide 1960 (a glutamic acid > lysine substitution at Position 628) in the 11th exon of the GPIIIa gene. This mutation was recently identified in a report as HPA-21bw. Next, it was determined that the cause of NAIT in both cases was the HPA-21bw antigen, as shown by the mothers' antibodies reacting with the mutated GPIIIa-transfected cells, but not with transfectants expressing wild-type GPIIIa. A molecular genetic screening for the HPA-21bw allele among Japanese donors showed that its genetic frequency in the population was 0.53% (10/1888), indicating that HPA-21bw occurs at a low but appreciable frequency in the population. Furthermore, in a retrospective study of 50 previous NAIT cases of unknown causes, we found one NAIT case associated with the HPA-21bw antibody. The two NAIT cases in this study represent the first ones to be associated with HPA-21bw in Japan. We identified the HPA-21bw allele from two unrelated Japanese infants with severe NAIT. We identified 10 individuals (1.06%) positive for the HPA-21bw allele from a genetic screening of 944 Japanese blood donors.

The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to MaternalABOGenotypes

Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.

P22.06: Treatment of severe fetal and neonatal alloimmune thrombocytopenia caused by anti‐HPA‐3b antibodies in monochorionic diamniotic twin pregnancy: a case report

P22.06: Treatment of severe fetal and neonatal alloimmune thrombocytopenia caused by anti‐HPA‐3b antibodies in monochorionic diamniotic twin pregnancy: a case report

A new Ser472Asn (Cab2a+) polymorphism localized within the αIIb “thigh” domain is involved in neonatal thrombocytopenia

A new platelet antigen, Cab2(a+), was identified in a case of severe neonatal alloimmune thrombocytopenia (<8 × 10(9)/L) in twins. Coding sequences of αIIb and β3 genes from parents were amplified and sequenced. CHO cell lines expressing wild-type or mutated forms of the complex were established to study the role of the mutation in alloimmunization and in αIIbβ3 functions. The father and twins were heterozygous for a single αIIb c.1508G>A mutation leading to a Ser472Asn substitution. Immunologic assays with transfected CHO cells revealed the Asn472 form of αIIbβ3 responsible for the Cab2(a+) epitope but not an Ala472 form. Using these cells lines we demonstrated that both Ser472Asn and Ser472Ala substitutions produced limited structural alteration as revealed by the reactivity of a panel of anti-αIIbβ3 monoclonal antibodies (MoAbs). Activated Asn472 and Ala472 forms of αIIbβ3 supported 1) binding of soluble fibrinogen and of the ligand mimetic MoAb PAC-1, 2) ligand-induced binding site epitopes exposure (MoAbs AP-5 and D3GP3), and 3) cell aggregation. Adhesion onto adsorbed fibrinogen was conserved and was specifically inhibited by MoAb AP-2 or peptide RGDS. Finally outside-in signaling was not affected. We have characterized a new low-frequency alloantigen (<1%) resulting from the Ser472Asn substitution in αIIb and shown this polymorphism to have a limited effect, if any, on the αIIbβ3 complex functions.

Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen‐7

Neonatal alloimmune thrombocytopenia (NAIT) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet (PLT) antigens inherited from the father. A healthy 30-year-old Japanese woman (Hit) gave birth to her second child after an uneventful pregnancy. Nine hours after birth, the infant presented with severe petechiae and a PLT count of 6 x 10(9)/L. To elucidate the maternal cause of NAIT in the infant, serologic and genetic studies, including PLT genotyping and sequence-based analysis, were conducted. Additionally, serologic screening for the new PLT antigen was performed. Serum from the NAIT infant's mother contained antibodies directed against a human PLT antigen (HPA) of the newborn. Using five-cell-lineage flow cytometry, we localized the antigen to a PLT glycoprotein (GP). Subsequent monoclonal antibody immobilization of PLT antigen assay and PLT immunofluorescence inhibition experiments localized the antigen to the GPIIIa subunit of the GPIIb/IIIa complex. GPIIIa localization was confirmed by sequence-based typing studies, which identified a 1297C>T (407proline>serine substitution) mutation on the ninth exon of the GPIIIa gene. This mutation identified the third allele of HPA-7. Anti-Hit(a) reacted with mutated GPIIIa-transfected cells but not with stable transfectants expressing wild-type GPIIIa. Serologic screening for Hit(a) in the Japanese population revealed a phenotypic frequency of approximately 0.0015. We identified a new third allele of HPA-7, which is characterized by a 1297C>T mutation in the GPIIIa gene. This 1297C>T allele was found in 0.15% of the Japanese population. An antibody against this antigen could be the cause of severe NAIT.

Low‐avidity HPA‐1a alloantibodies in severe neonatal alloimmune thrombocytopenia are detectable with surface plasmon resonance technology

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is mostly caused by maternal alloantibodies directed against the human platelet alloantigen (HPA)-1a. Currently, the serologic diagnosis of FNAIT is based on the characterization of the HPA alloantibodies in monoclonal antibody-based antigen-capture assays (e.g., MAIPA assay). Accumulated current evidence indicated that such assays may overlook some HPA-1a antibodies. This study employed surface plasmon resonance (SPR) technology using immunoaffinity-purified glycoprotein IIb/IIIa isoforms immobilized on biosensor chips to study the binding kinetics of HPA-1a alloantibodies from different FNAIT cases in real time. Analysis of HPA-1a alloantibodies from FNAIT cases (n = 9) in SPR showed a moderate relative response (22.2-69.7 resonance units [RU]) and slow antibody dissociation. After the dissociation phase, varying amounts of bound antibodies (41%-79%) remained on the chip. In contrast in HPA-1a alloantibodies from a patient suffering from posttransfusion purpura, a high relative response (approximately 490 RU) was observed at the end of the association phase and no dissociation of antibody binding was detectable. Of particular relevance, by the use of this SPR technique, HPA-1a alloantibodies were detected in two severe FNAIT cases that had determined as false negative by MAIPA assay. In SPR, these HPA-1a alloantibodies showed low-avidity nature characterized by gradual dissociation of antibody during the association phase and complete detachment of antibody binding after the dissociation phase. This high "off-rate" character of low-avidity HPA-1a alloantibodies indicates that such antibody binding is easily detachable by the extensive washing procedure of the MAIPA. Our results demonstrated that the SPR method can facilitate the diagnosis of clinically relevant low-avidity HPA-1a antibodies.

Mapping of Helper Epitopes to HPA-1a in Neonatal Alloimmune Thrombocytopenia with T-Cell Clones

Background: The major cause of severe neonatal allo-immune thrombocytopenia (NAITP) in Caucasians is fetal-maternal incompatibility for the human platelet antigen-1 (HPA-1), which is determined by the dimorphism Leu (HPA-1a) or Pro (HPA-1b) at amino acid position 33 of β3 integrin glycoprotein IIIa. Maternal responsiveness to HPA-1a shows a very strong association with DR52a (DRB3*0101) and 33Leu is thought to create a binding motif for this MHC class II molecule, thereby conferring helper T-cell responsiveness. At present, there are no preventative measures, reliable predictors of severity or screening procedures to identify women at risk of HPA-1a alloimmunization. Since the T-cells that help HPA-1a antibody production represent an attractive target for both screening assays and specific therapy, the aim was to define the epitope(s) they recognize in detail.Methods: From the peripheral blood of three HLA DR52a positive mothers with anti-HPA-1a antibodies and affected babies, we generated a total of six stable long-term CD4+ T-cell clones that respond specifically to the HPA-1a+ glycoprotein sequence. They have enabled us to characterize, for the first time, the fine specificity and restriction of the HPA-1a helper epitope. The core epitope was mapped by testing the responsiveness (proliferation and cytokine production) of the clones to panels of synthetic peptides spanning the HPA-1a 33Leu polymorphism, including sequences of different lengths, with selected single amino acid substitutions, and with the polymorphic residue located at different positions. Restriction was defined using antigen-presenting cells sharing HLA-DR and by flow cytometric analysis of staining with peptide-DR52a tetramers. The results, together with structural analyses, were used to model the interactions between MHC class II, HPA-1a peptide and specific helper T-cell receptor.Results: The 6 Th clones showed clear specificity for their HPA-1a epitope, even when naturally processed from whole platelets; they recognized only GPIIIa peptides (or platelets) with 33Leu and not 33Pro. The results of screening panels of linear peptides with 33Leu at different positions are consistent with a “core” epitope of 25WCSDEALPL33. The clones also specifically bound tetramerized DR52a complexed with a peptide spanning these residues. Together, the results show that 25Trp, 28Asp and 33Leu of HPA-1a are each important for anchoring respectively in pockets 1, 4 and 9 in DR52a, whereas 33Pro of HPA-1b sterically hinders docking in pocket 9. Extra residues 34Gly-35Ser did not affect T-cell recognition, but certain clones preferred N-terminal 24Ala or 23Cys-24Ala extensions. It has been previously reported that T-cells from alloimunized women with anti-HPA-1a recognize a 33Leu peptide cyclized by disulfide bridges (circular-Leu; 26C*SDEALPLGSPRC*38) but not to the circularized 33Pro equivalent. Our T-cell clones also responded moderately to this circular-33Leu peptide, demonstrating that 25Trp anchor at pocket 1 may not be essential when anchoring in pocket 4 and 9 are strong.Conclusions: Characterization of the HPA-1a specific Th clones reveals that they all recognize the core epitope GPIIIa 25Trp-33Leu, with the polymorphic 33Leu selectively anchoring it in the strongly predisposing HLA-DR52a. Although predicted to lie outside the peptide-binding groove of DR52a, extra N-terminal sequences promote optimal recognition by some T-cells, but are no longer required if the sequence is cyclized. Despite differences in TCR gene usage, the clones show remarkable consistency in fine specificity, supporting our previous evidence from polyclonal T-cell responses from women with anti-HPA-1a antibodies. The identification of a single “core” epitope, and the uniformity of restriction by DR52a in alloimmunized women, opens the way to both diagnostic and therapeutic exploitation in NAITP due to anti-HPA-1a.

Direct comparison between two quantitative assays in the measurement of maternal anti-HPA-1a antibody in neonatal alloimmune thrombocytopenia (NAIT)

Background Around 80% of severe neonatal alloimmune thrombocytopenia (NAIT) cases in the Caucasian population are due to anti-HPA-1a antibodies. However, the relationship between anti-HPA-1a antibody quantity and severity of NAIT has been subject to debate, possibly due to discrepant results between studies incorporating different assays (such as ELISA and MAIPA) and the number of samples. The aim of this study was to compare the level of maternal anti-HPA-1a antibodies in the same samples, using two different methods; quantitative ELISA and quantitative MAIPA. At the same time, the relationship between the maternal anti-HPA-1a antibody quantity and the newborn platelet count was examined. Materials and methods Plasma samples were obtained from HPA-1a negative mothers giving birth to children with different platelet counts (i.e. NAIT vs normal platelet count). The antibody levels were quantified blindly in the respective assays using standards calibrated against the international standard NIBSC 03/152. Results A linear correlation was observed between quantitative MAIPA and quantitative ELISA results. However, there were many individual variations giving a mean ratio of disagreement between the quantitative ELISA and quantitative MAIPA of 2.84. Furthermore, regression analysis revealed a significant relation between anti-HPA-1a antibody quantity measured by MAIPA, but not ELISA, and the newborn platelet count. Conclusion The results indicate that differences observed between various studies with regard to NAIT severity and anti-HPA-1a quantity could partly be due to different assays used.

The Development of Severe Anti-HPA 1a-Related Neonatal Alloimmune Thrombocytopenia Is Influenced by the Maternal ABO Type.

About 100 000 pregnant women were included in a screening and intervention program aimed to reduce morbidity and mortality related to neonatal alloimmune thrombocytopenia (NAIT). NAIT due to HPA 1a immunization have many features in common with hemolytic disease of the newborn (HDN) caused by RhD immunization. Platelets express blood group A and B antigens, and as described in HDN, ABO incompatibility between mother and fetus could possibly protect against immunization against HPA 1a. The aim of the study was to describe the ABO distribution among the immunized mothers and examine whether ABO status of the mother influenced the severity of thrombocytopenia in the newborn. ABO typing of HPA 1a immunized women was routinely performed by serological methods during the screening. ABO genotyping resolving the major alleles (A1, A2, B, O1, O1v or O2 alleles) of the women and their newborns was performed by PCR-RFLP methods. The ABO distribution among the immunized HPA 1a negative women was found to be similar to the normal distribution in the Norwegian population, which may indicate that the ABO type does not influence the immunization mechanism. However, we find that HPA 1a immunized women of blood group A have a higher risk of delivering a child with severe NAIT (platelet count < 50×109/L) than women with blood group O. Twenty percent of the immunized women with blood group O gave birth to children with severe NAIT, compared to 46% among the immunized blood group A mothers, resulting in a relative risk of 0.43 (95% CI 0.25–0.76). The ABO type of the newborn was not found to influence development of severe NAIT. The O1/O1v allele distribution among the immunized women with blood group O resembles the distribution reported for a Swedish population. However, only 2/22 (9.1%) pregnancies among the O1v negative blood group O mothers resulted in a newborn with severe NAIT, compared to 10/34 (29.4%) among the O1v-positive blood group O women, resulting in a relative risk of 0.31 (95% CI 0.07–1.28). The observation that the immune response against HPA 1a may have different consequences depending on the ABO blood group of the mother is interesting. O1v, also termed O02, constitutes a separate but ancient allelic lineage at the ABO locus and we are now in the process of examining if our observation is related to linkage disequilibrium between the ABO gene and one or more pregnancy-related immunoregulatory genes.

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

AbstractThe study's objective was to identify HPA 1a–negative women and to offer them an intervention program aimed to reduce morbidity and mortality of neonatal alloimmune thrombocytopenia (NAIT). HPA 1 typing was performed in 100 448 pregnant women. The HPA 1a–negative women were screened for anti–HPA 1a. In immunized women, delivery was performed by Cesarean section 2 to 4 weeks prior to term, with platelets from HPA 1a–negative donors reserved for immediate transfusion if petechiae were present and/or if platelet count was less than 35 × 109/L. Of the women screened, 2.1% were HPA 1a negative, and anti–HPA 1a was detected in 10.6% of these. One hundred seventy pregnancies were managed according to the intervention program, resulting in 161 HPA 1a–positive children. Of these, 55 had severe thrombocytopenia (< 50 × 109/L), including 2 with intracranial hemorrhage (ICH). One woman with a twin pregnancy missed the follow-up and had one stillborn and one severely thrombocytopenic live child. In 15 previous prospective studies (136 814 women) there were 51 cases of severe NAIT (3 intrauterine deaths and 7 with ICH). Acknowledging the limitation of comparing with historic controls, implementation of our screening and intervention program seemed to reduce the number of cases of severe NAIT-related complications from 10 of 51 to 3 of 57.

Delayed detectability of anti‐HPA‐3a by the MAIPA assay in a severe neonatal alloimmune thrombocytopenia, but successful transfusion of incompatible donor platelets: a case report

Vox SanguinisVolume 91, Issue 2 p. 181-183 Delayed detectability of anti-HPA-3a by the MAIPA assay in a severe neonatal alloimmune thrombocytopenia, but successful transfusion of incompatible donor platelets: a case report K. Schallmoser, K. Schallmoser Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this authorJ. Kutschera, J. Kutschera Division of Neonatology, Paediatric Department, Medical University of Graz, AustriaSearch for more papers by this authorS. Macher, S. Macher Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this authorS. Ulrich, S. Ulrich Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this authorP. Eichler, P. Eichler Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, GermanySearch for more papers by this authorS. Panzer, S. Panzer Clinic for Blood Group Serology, Medical University of Vienna, AustriaSearch for more papers by this authorG. Lanzer, G. Lanzer Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this author K. Schallmoser, K. Schallmoser Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this authorJ. Kutschera, J. Kutschera Division of Neonatology, Paediatric Department, Medical University of Graz, AustriaSearch for more papers by this authorS. Macher, S. Macher Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this authorS. Ulrich, S. Ulrich Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this authorP. Eichler, P. Eichler Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, GermanySearch for more papers by this authorS. Panzer, S. Panzer Clinic for Blood Group Serology, Medical University of Vienna, AustriaSearch for more papers by this authorG. Lanzer, G. Lanzer Department of Blood Group Serology and Transfusion Medicine andSearch for more papers by this author First published: 05 July 2006 https://doi.org/10.1111/j.1423-0410.2006.00809.xCitations: 13 : Katharina Schallmoser, Department for Blood Group Serology and Transfusion Medicine, Medical University of Graz, Auenbruggerplatz 3, A-8036 Graz, Austria E-mail: katharina.schallmoser@klinikum-graz.at Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume91, Issue2August 2006Pages 181-183 RelatedInformation

Antigen-positive platelet transfusion in neonatal alloimmune thrombocytopenia (NAIT)

Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal incompatibility most commonly induced by maternal anti-HPA-1a, IgG alloantibodies against a polymorphic epitope of the glycoprotein IIb/IIIa complex in approximately 97.5% of white patients. Current guidelines recommend transfusion of immunologically compatible platelets to prevent cerebral hemorrhage, the most severe complication in affected newborns. Such platelet concentrates, however, are often not readily available. In a retrospective analysis in German and Canadian centers, 27 newborns with NAIT were identified who received platelets from random donors. Unexpectedly, 24 of 27 newborns showed an increase above a threshold of 40 x 10(9) platelets per liter, with moderate (n = 8) or significant (n = 16) platelet count increments (more than 80 x 10(9)/L). We conclude that transfusion of platelet concentrates from random donors is an appropriate strategy in the management of unexpected, severe NAIT predominantly in first pregnancies, pending the availability of compatible platelets.