European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia

The aims of this study were to determine whether the severity of fetomaternal alloimmune thrombocytopenia (FMAIT) in the current pregnancy could be predicted from the history of FMAIT in previous pregnancies, and to assess the effects of different types of antenatal intervention. Fifty-six fetuses were studied that all had a sibling affected by FMAIT due to human platelet antigen 1a (HPA-1a) alloimmunization. Cases with a sibling history of antenatal intracranial haemorrhage (ICH) or severe thrombocytopenia (platelet counts of < 20 x 109/l) had significantly lower pretreatment platelet counts than cases whose siblings had less severe thrombocytopenia or postnatal ICH. Maternal therapy resulted in a platelet count exceeding 50 x 109/l in 67% of cases. None of the fetuses managed by serial platelet intrauterine transfusions (IUT) suffered ICH following treatment. However, several serious complications arose with fetal blood sampling (FBS). Overall, intervention improved outcome, as three study cases suffered from antenatal ICH and three others died whereas 15 study cases had a sibling with an ICH, eight of whom died. The results of this study suggest that the start of therapy can be stratified on the basis of the sibling history of FMAIT, and support the use of maternal therapy as first-line treatment.     

The management of alloimmune neonatal thrombocytopenia.

Neonatal alloimmune thrombocytopenia (NAITP), defined as thrombocytopenia (platelet count < 150 x 10(9)/l) due to transplacentally acquired maternal platelet alloantibodies, occurs in approximately 1 per 1200 live births in a Caucasian population. In such a population, the majority (> 75 percent) of cases are due to fetomaternal incompatibility for the platelet specific alloantigen, HPA-1a (P1A1, Zwa). Incompatibility for the HPA-5b (Bra) alloantigen is the next most frequent cause of NAITP in Caucasians; much less common is NAITP due to incompatibility for HLA, blood group ABO or other platelet-specific antigens. In non-Caucasian populations (e.g. Orientals) HPA-1a incompatibility is a rare cause of NAITP and other alloantigens e.g. HPA-4b (Penb, Yuka) are implicated. The greatest clinical challenge relates to the antenatal management of pregnant women alloimmunized to the HPA-1a (P1A1, Zwa) antigen, and particularly the subset of such women who have a history of a previously affected infant with severe thrombocytopenia and/or intracranial hemorrhage (ICH). The risk of antenatal ICH in the fetus of such women is high enough to merit intervention, either weekly infusion of high-dose intravenous immunoglobulin G (IVIG) with or without corticosteroids given to the mother (the preferred approach in North American centres), or repeated in-utero fetal platelet transfusions (the preferred treatment approach in some European centres). Post-natal management of severely affected infants centres on the rapid provision of compatible antigen-negative platelets harvested from the mother or a phenotyped donor. The value of antenatal screening programs to detect 'at risk' alloimmunized women during pregnancy continues to be debated.     

Severe fetomaternal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-1a in a mother with a rare and silenced ITGB3*0101 (GPIIIa) allele

BACKGROUND AND OBJECTIVES: Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal antibodies against a human platelet antigen (HPA) present on fetal, but absent from maternal platelets. We identified and characterized a case of FMAIT due to anti-HPA-1a in a mother with an HPA-1a1b genotype. MATERIALS AND METHODS: The first child of a 29-year-old mother presented with a petechial rash and a platelet count of 8 x 10(9) per l. Upon routine serological investigation, a discrepancy between the HPA-1a genotype and phenotype prompted the sequencing of the 15 exons of the ITGB3 (integrin beta3, GPIIIa and CD61) gene in the mother. RESULTS: The mother was genotypically HPA-1a1b heterozygous but phenotyped as HPA-1a negative. Sequencing of the ITGB3 exons confirmed HPA-1a1b heterozygosity, but also identified a novel single nucleotide insertion in exon 10 leading to a frameshift and premature termination at amino acid 471 of ITGB3. Maternal anti-HPA-1a was detected but with a pattern typical for a low-affinity antibody. Three transfusions of HPA-1a and -5b negative neonatal platelet concentrates were required to return to a safe platelet count. CONCLUSION: A rare ITGB3 allele was uncovered by the investigation of a severe case of alloimmune thrombocytopenia in a mother with HPA-1a antibodies who genotyped as HPA-1a1b.     

Prediction of the fetal status in noninvasive management of alloimmune thrombocytopenia

Fetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the fetus and in an otherwise healthy newborn. To counter the consequences of severe fetal thrombocytopenia, antenatal therapies have been implemented. Predictive parameters for fetal severe thrombocytopenia are important for the development of noninvasive strategy and tailored intervention. We report here data concerning 239 pregnancies in 75 HPA-1bb women. Analysis of the index cases (diagnosis of fetal/neonatal alloimmune thrombocytopenia) did not show any significant correlation between the severity of the disease and the maternal genetic background (ABO blood group and HLA-DRB3 allele). Subsequent pregnancies were managed, and therapy effectiveness was evaluated. The highest mean newborn platelet count was observed for a combination of intravenous immunoglobulin and steroids (135 × 10?/L; 54 newborns) compared with intravenous immunoglobulin alone (89 × 10?/L; 27 newborns). The maternal anti-HPA-1a antibody concentration measured before any treatment and before 28 weeks of gestation was predictive of the fetal status. The weighted areas under curves of the maternal alloantibody concentrations were predictive of therapy response. To conclude, this large retrospective survey gives new insights on maternal predictive parameters for fetal status and therapy effectiveness allowing noninvasive strategies.     

Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice,an international approach

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.     

Management of Fetal Alloimmune Thrombocytopenia by Weekly in utero Platelet Transfusions

Alloimmune neonatal thrombocytopenia (ANT) may cause intracranial haemorrhage in utero as well as at delivery. Recent management has concentrated on attempts to minimise fetal thrombocytopenia and prevent its complications. This report describes further experience with the use of repeated intravascular transfusions of compatible platelets in utero. The patient studied had already had one infant with intracranial haemorrhage due to ANT. In her next pregnancy, weekly intra-uterine platelet transfusions were given from 26 weeks, but intra-uterine death occurred at 30 weeks after the mother had a heavy fall. In her most recent pregnancy, weekly intravascular transfusions of platelets were given by cordocentesis from 29 to 34 weeks. The fetal platelet count was maintained above 30 X 10(9)/l for almost all of the last 6 weeks of pregnancy before delivery of a normal infant by Caesarean section at 35 weeks' gestation. This approach is effective in preventing severe fetal thrombocytopenia in the last trimester of pregnancy and is contrasted with alternative treatments of ANT. Further data are required to determine the efficacy and risks of these treatments.     

A new efficient tool for non-invasive diagnosis of fetomaternal platelet antigen incompatibility

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the consequence of platelet destruction by maternal alloantibodies against fetal human platelet antigens (HPA). This may result in intracranial haemorrhages (ICH) or even fetal death. Currently, fetal HPA genotyping is performed using invasive procedures. Here, we carried out a proof-of-concept study for non-invasive prenatal diagnosis of fetal platelet genotyping in four HPA systems (HPA-1, -3, -5 and-15) by droplet digital polymerase chain reaction (ddPCR) using cell-free DNA extracts from the plasma of 47 pregnant women with suspected, or history of, FNAIT. Results showed that 74% (35/47) of pregnant women presented incompatibility in at least one HPA system, and 38% (18/47) of cases presented HPA-1 incompatibility, including nine women with multiple incompatibilities. ICH occurred in one case of profound fetal thrombocytopenia with HPA-15 incompatibility, confirming the need for non-invasive prenatal genotyping in systems other than HPA-1. Fetal HPA genotypes predicted by ddPCR were confirmed in all FNAIT cases after amniocentesis or delivery. Fetal HPA genotyping on maternal plasma based on ddPCR is a fast, safe and reliable non-invasive method. This technique will be useful for the early identification of pregnancies at high risk of FNAIT requiring antenatal management to minimize the risk of fetal/neonatal haemorrhage.     

Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids — more questions than answers

The optimal antenatal therapy for fetal thrombocytopenia has not been determined. We analysed 37 cases managed by maternal therapy and observed a successful outcome of maternal treatment in 26% of IvIgG cases and in 10% of steroid-treated cases. The significance of a plateau of the fetal platelet counts during pregnancy, 41% of IvIgG cases and 20% of cases treated with steroids, is uncertain. It may indicate a stabilization of thrombocytopenia, hence a beneficial effect of therapy, or the natural course of the platelet count in a low-risk pregnancy. Overall outcome was unpredictable, but amongst the therapy failures there were proportionally more severely affected siblings. Further multicentre studies are necessary to establish the optimal antenatal management of high-risk pregnancies.     

Alloimmune thrombocytopenia of the fetus and the newborn

Fetal/neonatal alloimmune thrombocytopenia results from a maternal alloimmunization against fetal platelet antigens. Care must be taken in making a correct diagnosis that eliminates other causes of thrombocytopenia that may occur during pregnancy. Biological diagnosis is normally made by platelet genotyping and search for the maternal alloantibody using monoclonal antibodies in an antigen capture assay. Fetal alloimmune thrombocytopenia, when severe, may result in intracerebral hemorrhage leading to hydrocephalus and death of the fetus. Neonatal alloimmune thrombocytopenia may be present in an otherwise healthy infant. While screening procedures are not in place to detect fetal/neonatal alloimmune thrombocytopenia, it is true that fetal hydrocephalus, unexplained fetal thrombocytopenia with or without anemia, or recurrent miscarriages should be adequate indicators for suspecting fetomaternal alloimmune thrombocytopenia. Multiparous women with a history of giving birth to at least one alloimmune thrombocytopenic infant should be carefully monitored in subsequent pregnancies. Postnatal management of neonatal alloimmune thrombocytopenia involves compatible platelet transfusion in the neonate. Antenatal management of fetal alloimmune thrombocytopenia is controversial and includes a combination of maternal intravenous gamma globulin (i.v.IgG) administration, intrauterine platelet transfusions, and corticosteroid therapy, while monitoring fetal platelet counts closely throughout the course of pregnancy. Screening of pregnant women may become a public health issue only after antenatal therapy is more standardized.     

Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-3a

Background and Objectives: Neonatal alloimmune thrombocytopenia is usually attributable to HPA-la antibodies. We report a case of parental platelet antigen incompatibility associated with a severe neonatal thrombocytopenia secondary to alloimmunization to HPA-3a. Materials and Methods: Platelet antibodies were detected by the monoclonal antibody-specific immobilization of platelet antigens, genotyping of the platelets by PCR, and HLA typing by serologic procedures and PCR. Results: Genotyping of maternal and paternal platelets confirmed the incompatibility in the HPA-3a system. It is noteworthy that the mother is of the HLA type DRB3*0101, is ABO-incompatible with her husband, and also has HLA class I antibodies. Conclusion: Severe neonatal thrombocytopenia associated with HPA-3a alloimmunization is infrequent and all the factors mentioned above could have played a role in the severity of the disease.     

Spontaneous Rise of Fetal Platelet Counts Despite Increasing anti-HPA-5b Antibodies

Background and objectives: Maternal anti-HPA alloantibodies are a rare cause of severe fetal thrombocytopenia. So far there have been no reports on the dynamics of maternal anti-HPA-5 during gestation and its effect on the fetus. Materials and methods: We monitored maternal anti-HPA-5b antibody titers and fetal platelet counts during gestation in a woman with known anti-HPA-5b alloimmunization. The patient was a 32-year-old woman in her third pregnancy. The 1st pregnancy and delivery of a healthy child had been uneventful. At delivery, anti-HPA-5b was detectable in the maternal serum. A 2nd pregnancy ended in early miscarriage. Results: A steady rise in the alloantibody titer was recorded throughout the 3rd pregnancy. Therefore, cordocentesis was performed at 28 weeks of gestation (platelet count 76×10⁹/l). Serial platelet transfusions were administered to the fetus at 28, 32, and 37 weeks of gestation. The platelet counts rose spontaneously thereafter and were 220×10⁹/l at delivery, despite an increase in the anti-HPA-5b antibody titer. The child developed normally during the first year of life. Conclusions: This case illustrates the spontaneous recovery of fetal platelet counts in late pregnancy despite a rise in maternal alloantibody titer.     

Antenatal screening for fetal alloimmune thrombocytopenia: the results of a pilot study

Summary. Feto-maternal incompatibility for the human platelet antigen HPA-la is an important cause of severe fetal thrombocytopenia. The incidence is 1 in 1000-2000 pregnancies, which is more common than other conditions for which screening is presently carried out. Antenatal diagnosis and management are now available, but only for subsequent siblings following diagnosis of a previously affected infant. This study describes a pilot prospective screening programme for the antenatal detection of feto-maternal alloimmune thrombocytopenia (FMAIT) due to HPA-la incompatibility. 3473 women were typed for HPA-la using a method designed for large-scale typing. 71 women found to be HPA-la negative were further tested for HLA-DR52a as a risk factor for alloimmunization. All women were monitored for the development of anti-HPA-la throughout pregnancy and a cord full blood count was taken at delivery. Two affected pregnancies were found and treated: a singleton pregnancy was treated antenatally and a twin pregnancy after delivery. The study showed that screening for FMAIT could be established within the pre-existing antenatal red cell serology programme. It was concluded that screening should be based on platelet typing and offered regardless of parity. Further stratification, combining DR52a typing and HPA-la antibody screening, although focusing on the group of women at greater risk, may not identify all affected pregnancies. Confirmation of the diagnosis and severity of FMAIT continues to depend on fetal blood sampling during pregnancy or cord blood samples after birth.     

Antibody formation in pregnant women with maternal-neonatal human platelet antigen mismatch from a hospital in northern Taiwan

Neonatal alloimmune thrombocytopenia (NAIT) is a clinical syndrome that resembles hemolytic disease of the newborn, affecting the platelets only. The thrombocytopenia results from the maternal alloantibodies reacting with specific human platelet antigens (HPAs) on the fetal platelets. Forty-four maternal plasma samples were screened for platelet alloantibodies using qualitative solid phase enzyme-linked immunosorbent assay (ELISA) commercial kit (LIFECODES Pakplus, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA), and both the maternal and the corresponding cord blood samples were genotyped (LIFECODES ThromboType, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA). HPA genotyping results correlated with the genetic frequencies in the Taiwan population. A total of 34 newborns (77.3%) had partial HPA genotyping mismatches with the corresponding mothers. The most common partial mismatches between mothers and neonates in HPA genotypes were 13 (29.5%) in both HPA-3b and HPA-15a, followed by 12 (27.3%) in HPA-15b, and 8 (18.2%) in HPA-3a. The frequencies of homozygotic mother with heterozygotic neonate were 15.9% in both HPA-3a and HPA-15b, 9.1% in HPA-15a, 6.8% in HPA-3b, and 2.3% in both HPA-2a and HPA-6a. In this study, maternal HPA antibodies were found in five samples, whereas HLA class I antibodies were found in seven maternal plasma samples from the antibody screen. The results from this study have demonstrated that HPA mismatch is not the main cause for the production of HPA alloantibodies.     

HPA-5b (Bra) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases

Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia (NAIT). The HPA-1a (PIA1, Zwa) antigen is by far the most common antigen implicated in NAIT. However, today another antigen often linked with that affection is HPA-5b (Br(a)). This is a report of 39 cases of NAIT involving the HPA-5b antigen. Thrombocytopenia may be of grave consequence. Three infants developed intracerebral haemorrhages (ICH). Of these, one died presumably as a consequence of ICH. Central nervous system (CNS) sequelae in the neonatal period was observed in two children. The potential hazards of death or disabling neurologic sequelae following intracerebral haemorrhage call for rapid and reliable diagnosis and effective therapy. Because there is high risk that subsequent pregnancies might be also affected by NAIT, the mothers of a previously affected child should be managed similarly to the HPA-1b mothers (PIA2, Zwb). The antenatal diagnosis of thrombocytopenia should be made and if necessary the in utero therapy instituted.     

Pregnancy in patients with beta-thalassemia intermedia: outcome of mothers and newborns

Little is known about the outcome of pregnancy in women with beta-thalassemia intermedia (TI). Over 10 years, maternal and neonatal outcomes of women with TI followed at a single thalassemia center were reviewed. Nine spontaneous pregnancies in five women with TI were studied. Six pregnancies resulted in live newborns; two were complicated by first-trimester abortions and one by an unexplained intrauterine fetal death at 36 weeks' gestation. Two patients had splenectomy before pregnancy: one required cesarean delivery and splenectomy at 31(2/7) weeks' gestation for worsening hemolytic anemia and thrombocytopenia and another had splenectomy 8 weeks postpartum for symptomatic hypersplenism. Two patients had received transfusions before pregnancy, and two required them for the first time during pregnancy and developed antibodies, which contributed to worsening of their anemia and repeated transfusions. The mean number of transfusions received during pregnancy was 8.0 +/- 5.2 units. The mean lowest hemoglobin level in pregnancy was 5.2 +/- 2.0 g/dl. Cesarean delivery was performed in 42.9% of cases. Mean gestational age at delivery was 36.7+/- 3.1 weeks with intrauterine growth restriction (IUGR) complicating 57.1% of cases. In conclusion, IUGR complicates more than half of pregnancies with TI. Transfusions are needed in most cases, even in non-transfusion-dependent patients. Postpartum splenectomy might be necessary in some patients.     

Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets

Neonatal alloimmune thrombocytopenia (NAIT) can cause severe bleeding in the central nervous system (CNS) and death or severe neurologic sequelae. The expression of the PLA1 antigen is detectable as early as 19 weeks of gestation. Alloimmunization can therefore lead to fetal thrombocytopenia very early in pregnancy. Until recently, we have had no means of detecting and assessing the severity of fetal thrombocytopenia during pregnancy. The level of the maternal antibody is not of a predictable value since 20% of the mothers had no circulating antibodies in our series. An alternative approach is to carry out investigations on fetal blood samplings. This management leads to an exact knowledge of the fetal status and antenatal diagnosis is feasible as early as the 21st week of gestation. Early diagnosis facilitates appropriate management and makes possible such therapeutic options as in utero maternal platelet transfusions. We report our experience in the antenatal diagnosis and management of nine cases with in utero transfusion in the six cases with severe thrombocytopenia. All neonates did well, with no signs of bleeding at birth. No side effects of therapy were noted after a period ranging from 6 months to 3 years.     

Efficacy of HPA-1a (PlA1)-negative platelets in a patient with post-transfusion purpura

Post-transfusion purpura (PTP) is a rare form of alloimmune thrombocytopenia that is self-limited but which carries a 10-15% mortality related to fatal hemorrhage. Immunomodulatory therapies such as plasmapheresis and intravenous immunoglobulin G (IVIg) can shorten the duration of thrombocytopenia. However, in a bleeding patient with PTP, more urgent therapy may be required. Textbooks of hematology [1-3] as well as reports in the literature [4,5] suggest that patients do not respond to platelet transfusions. We report a case of PTP in a patient homozygous for HPA-1b who suffered an intracranial hemorrhage. The patient was treated with IVIg and plasmapheresis. Because of her life-threatening bleeding, we also transfused the patient with HPA-1a-negative platelets. These transfusions consistently resulted in transient improvements in her platelet counts and may have limited the degree of intracranial bleeding. Our experience suggests that transfusion of platelets that lack the offending epitope in patients with PTP may be efficacious.     

Monitoring Anti-HPA-1a Platelet Antibody Levels during Pregnancy Using the MAIPA Test

Anti-HPA-1a platelet antibody levels in pregnant women with a history of fetomaternal alloimmune thrombocytopenia (FMAIT) were monitored longitudinally using the monoclonal antibody immobilisation of platelet antigens (MAIPA) assay, in order to examine any variation in optical density (OD) readings obtained over the course of pregnancy and after delivery. Seven women were selected; 4 were studied retrospectively and 3 prospectively (the latter being treated with intravenous gammaglobulin; IVGG). Levels of anti-HPA-1a were measured at various intervals after delivery of the first affected infant, to post delivery of the following affected infant. A decrease in MAIPA OD was demonstrated in all patients during the course of these pregnancies. This assay is a useful tool for monitoring anti-HPA-1a in women with a history of infants affected with FMAIT. A maternal antibody 'resting' level prior to, or early in the first trimester, must be established for comparison.     

Successful treatment of platelet transfusion refractoriness: the use of platelet transfusions matched for both human leucocyte antigens (HLA) and human platelet alloantigens (HPA) in alloimmunized patients with leukaemia

Six patients, 4 with acute myeloid leukaemia and 2 with a myelodysplasia syndrome who were refractory to random donor platelet transfusions and alloimmunized to human leucocyte antigens (HLA) and human platelet alloantigens (HPA), were treated with HLA-and HPA-matched platelet transfusions. In all the patients refractoriness and alloantibodies to HLA as well as HPA-1b or HPA-5b were detected simultaneously. Sixty-seven transfusions (445 units) of HLA-and HPA-matched platelets were given and responses to them were, in general, satisfactory in all the patients. No major spontaneous bleeding occurred. Four patients underwent bone marrow transplantation despite alloimmunization. The percentages of platelet transfusion days with a platelet nadir below 20×10⁹/l were 88% for the last 3 random donor platelet transfusions and 39% for the first 3 HLA-and HPA-matched platelet transfusions, respectively (p=0.009, Fisher's exact test). Four patients received also HLA-matched platelets, but responses to them were poor. The small number of transfusions with HLA-matched platelets precluded comparisons to either the random donor or HLA-and HPA-matched platelet transfusions. It seems that HLA-and HPA-alloimmunized patients can be successfully supported with HLA-and HPA-matched platelet concentrates.     

The platelet α2-integrin (GPIa) nucleotide-807 polymorphism is not associated with a risk for maternal–fetal human platelet antigen-5 incompatibility

Alloimmunization against human platelet antigen (HPA)-5 may lead to neonatal alloimmune thrombocytopenia. The HPA-5 dimorphism is expressed on the platelet α2β1 integrin. The density of this receptor is associated with another dimorphism of the α2β1 integrin (nucleotide-807C/T). We hypothesized that anti-HPA-5b-induced neonatal thrombocytopenia is more likely to occur if the receptor is expressed at high than at low levels. Among 933 mother–child pairs, we identified 79 HPA-5aa mothers giving birth to a HPA-5ab offspring. Seventeen mothers had HPA-5b antibodies, but the offspring had a normal platelet count. We genotyped the offspring and mothers for the α2-807C/T dimorphism to evaluate its relationship to antibody formation. There was no difference between the frequency of the 807C/T dimorphism among children delivered from alloimmunized mothers and those from mothers without antibodies (P>0.3). The frequency of the 807C/T dimorphism was not different in the two maternal groups. In three maternal–fetal incompatibilities, we observed at delivery normal platelet counts of platelets typed HPA-5b-α2807T, despite increasing maternal antibody titers during the pregnancy. Our data do not support the hypothesis that the 807C/T dimorphism in the HPA-5ab children is a predisposing factor to either elicit alloimmunization against HPA-5b or for neonatal alloimmune thrombocytopenia. Received: 5 October 1999 / Accepted: 1 December 1999