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Background: Neonatal alloimmune thrombocytopenia is a rare but potentially severe postnatal complication caused by maternal allo‐antibodies against platelet antigens of the newborn. In relatively few cases, immunisation against low‐frequency antigens has been reported. Methods: Platelet antigens of a newborn with severe thrombocytopenia and his family members were investigated by serological and molecular biological methods. A real‐time PCR assay was developed to reliably detect this mutation in pools of DNA from up to seven individuals. Results Serological testing showed positive reactions of maternal plasma with paternal platelets but not with conventional platelet donor panels. Sequencing of the ITGB3 gene revealed a G > A polymorphism in position c.1915 of exon 12 for the father, the newborn and three of four paternal relatives. Screening of samples from a local population of 1575 Caucasian blood donors identified only a single individual with this mutation. Conclusion: This finding of a previously unreported private platelet antigen demonstrates that the identification of the target glycoprotein by MAIPA assay followed by sequencing of the affected gene can be combined with an efficient population screening by real‐time PCR with pooling of DNA samples. [ABSTRACT FROM AUTHOR]

Alloimmunization against platelet antigens causes complications in transfusion settings as platelet transfusion refractoriness and post-transfusion purpura, as well as in pregnancy, causing fetal/neonatal alloimmune thrombocytopenia. Strategies for the laboratory investigations depend on a repertoire of serological and molecular assays and are often dependent on timing and objective. Technical improvements have led to a number of sophisticated methods for alloantigen typing and alloantibody identifications during the last decade; however, some traditional methods are still beneficial. The laboratory investigations should ensure that the causative antibody specificities are identified as soon as possible to support the correct diagnosis and guide the selection of compatible platelets if needed. [ABSTRACT FROM AUTHOR]

Background and objectives: To detect HPA‐15 alloantibodies, we previously developed a human platelet antigen 15 (HPA‐15)‐expressing cell line‐based modified rapid monoclonal antibody immobilization of platelet antigen (CL‐MR‐MAIPA) assay. In this study, the protocol was modified for easier performance by introducing the mixed‐passive haemagglutination (MPHA) principle. Material and methods: In total, 20 samples that tested negative for HPA alloantibodies and eight that tested positive for HPA‐15 alloantibodies (two and six positive for HPA‐15a and HPA‐15b antibodies, respectively) by CL‐MR‐MAIPA assay were used in this study. HPA‐15 cell lines were incubated with serum/plasma and then solubilized. The lysate was transferred to a round‐bottom well, which was coated with anti‐human CD109 monoclonal antibodies. After incubation and repeated washings, sheep red blood cells, coated with anti‐human IgG, were added to the wells. Haemagglutination was assessed the next day. Results: The proposed cell line‐based immune complex capture‐dependent mixed‐passive haemagglutination (CL‐IC‐MPHA) assay consisted of four steps, but required only 2 h to perform, except for overnight incubation for haemagglutination. Two HPA‐15a alloantibody samples were reactive only for HPA‐15a cells, and six HPA‐15b alloantibody samples were reactive only for HPA‐15b cells with the CL‐IC‐MPHA assay. The 20 samples that tested negative for HPA alloantibodies did not react with HPA‐15a or HPA‐15b cells. These data indicated that the CL‐IC‐MPHA assay was highly specific and sensitive. Unfortunately, the CL‐IC‐MPHA assay's analytic sensitivity was twofold to eightfold lower than that of the CL‐MR‐MAIPA assay. Conclusion: A novel, easy‐to‐perform protocol was successfully developed to detect HPA‐15 alloantibodies with high specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare but potentially very serious bleeding condition affecting the fetus/newborn. The vast majority (>80%) of FNAIT cases among Caucasians, and the most serious one, are caused by maternal antibodies to the human platelet antigen 1a (HPA‐1a). The clinical consequences of FNAIT span a continuum from no symptoms to intracranial haemorrhage (ICH) and intrauterine death. The incidence of FNAIT‐associated ICH has been estimated to be around 1 in 10 000 newborns. For many reasons, FNAIT has not been considered for prophylactic efforts similar to those that have been used for the prevention of HDFN, caused by antibodies against RhD: first, HPA‐1a typing kits are not well suited to the workflow in immunohaematology laboratories; secondly, the costs associated with HPA‐1a typing of all pregnant women have been a hindrance; thirdly, there is no international consensus regarding the optimal antenatal management of HPA‐1a‐immunized women identified in a screening programme; fourthly, it has generally been believed that immunization against HPA‐1a mostly takes place during the first incompatible pregnancy, and finally, there is yet no medicinal product available that can prevent HPA‐1a‐immunization in the same way as anti‐D can prevent RhD immunization. Implementation of HPA‐1a typing of all pregnant women has been discussed by the health authorities in several European countries. The abovementioned five hindrances for FNAIT screening and the Wilson and Jungner criteria for screening programmes will be discussed in the light of recent advances within FNAIT research. [ABSTRACT FROM AUTHOR]

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a severe bleeding disorder which can result in intracranial haemorrhage (ICH), leading to death or neurological sequelae. In Caucasians, maternal anti‐HPA‐1a antibodies (abs) are responsible for the majority of FNAIT cases. However, the correlation between fetal platelet counts and risk of bleeding is loose. ICH was also observed in FNAIT cases with platelet counts within reference ranges. These observations question the exclusive role of thrombocytopenia in ICH. Recently, we observed stronger binding of anti‐HPA‐1a antibodies from mothers with ICH‐positive (+ICH) FNAIT to endothelial cell‐derived αvβ3 when compared to anti‐HPA‐1a from ‐ICH. Differential absorption experiments demonstrated that anti‐HPA‐1a is not a single antibody entity. Sera from immunized women may contain three different subspecificities: anti‐β3, anti‐αIIbβ3 and anti‐αvβ3. Anti‐β3 appears to be the dominant subtype of anti‐HPA‐1a. However, anti‐αvβ3 was only found in +ICH sera, and only the anti‐αvβ3, but not anti‐β3 subtype, induced apoptosis and disturbed tube formation of endothelial cells in vitro. Therefore, we believe that this anti‐HPA‐1a subtype plays a significant role in the development of ICH. Together with other subtypes, anti‐αvβ3 may trigger bleeding in a threshold model of FNAIT/ICH, where bleeding occurs if yet undefined levels of anti‐endothelial (loss of integrity) and/or antiplatelet (low platelet count) activities are achieved. Thus, defining anti‐HPA‐1a subtypes may have significant potential in the prediction of ICH. With upcoming nation‐wide screening programmes, detection of anti‐HPA‐1a subtypes could prove helpful to allocate treatment to appropriate (at‐risk) cases, especially in countries with restricted resources. [ABSTRACT FROM AUTHOR]

The immune response against platelets is a complex process involving many aspects of the innate and adaptive immune system. Immune destruction of platelets and megakaryocytes and the thrombocytopenia that ensues can cause different clinically significant haematological disorders such as foetal and neonatal alloimmune thrombocytopenia (FNAIT), transfusion‐induced platelet refractoriness or immune thrombocytopenia (ITP). These conditions are frequently difficult to manage so an understanding of the biological nature of these adverse conditions is critical for an understanding of how to potentially reduce them. Superimposed on these immune platelet attack mechanisms are the immune characteristics of the platelets themselves. This paper will give an overview of how the immune system recognizes platelet antigens and mounts efficient effector mechanism to mediate thrombocytopenia. It will also present evidence to suggest that platelets also play a role in stimulating these responses and suppressing them: a scenario where the ‘prey’ can become the ‘predator’. [ABSTRACT FROM AUTHOR]

Problem Fetal and neonatal alloimmune thrombocytopenia is an alloimmune disorder resulting from platelet opsonization by maternal antibodies that destroy fetal platelets. As there is no antenatal screening or immunization to prevent sensitization, selection of high-risk population or the prevention of antenatal sensitization is significantly limited. Method of study (i) A case report of ante- and postnatal management of a woman with paternal homozygosity for human platelet antigen-1( HPA) incompatibility. (ii) A retrospective case-control study of 11 confirmed FNAIT patients, 8 possible- FNAIT women, and 10 women with confirmed ITP. Result Antenatal screening, prevention of maternal sensitization by serial monitoring and immunosuppression with prednisone and intravenous immunoglobulin G ( IVIG) infusion resulted in two successful pregnancies without sensitization. Conclusion Screening for couples at risk and prednisone and/or IVIG treatment is an option for women with paternal homozygosity for offending HPA antigen to prevent antenatal sensitization. HPA incompatibility is associated with increased Th1 immunity and NK cell cytotoxicity. [ABSTRACT FROM AUTHOR]

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs in c. 1 in 1000 births and is caused by maternal antibodies against human platelet alloantigens that bind incompatible fetal platelets and promote their clearance from the circulation. Affected infants can experience bleeding, bruising and, in severe cases, intracranial haemorrhage and even death. As maternal screening is not routinely performed, and first pregnancies can be affected, most cases are diagnosed at delivery of a first affected pregnancy. Unlike its erythrocyte counterpart, Haemolytic Disease of the Fetus and Newborn, there is no prophylactic treatment for FNAIT. This report will review recent advances made in understanding the pathogenesis of FNAIT: the platelet alloantigens involved, maternal exposure and sensitization to fetal platelet antigens, properties of platelet Immunoglobulin G antibodies, maternal-fetal antibody transport mechanisms and efforts to develop an effective FNAIT prophylaxis. [ABSTRACT FROM AUTHOR]

Background Fetal or neonatal alloimmune thrombocytopenia ( FNAIT) results from a maternal alloimmunization against fetal platelet antigens. Since the implementation of serological methods for the detection of antiplatelet alloantibodies, it has been demonstrated that anti- HPA-3a alloantibodies have considerable heterogeneity. Consequently, the serologic diagnosis of FNAIT may be hampered, despite severe clinical signs and the absence of other causes of thrombocytopenia. Here, we report the first HPA-3a feto-maternal alloimmunization observed in the Chinese population. Case study A 28-year-old woman gave birth to her first child. After 2 h of life, the newborn presented signs of multiple subcutaneous bleeding and severe thrombocytopenia (7 × 109 platelets/l). Three years later, the woman gave birth to a second newborn, with petechial and signs of bleeding at 15 min of life. Brain ultrasound revealed the presence of an intracranial haemorrhage. The newborn recovered after 23 days. Results Investigations revealed the presence of a feto-maternal HPA-3a incompatibility (mother: HPA-3bb; newborn: HPA-3ab). Maternal anti- HPA-3a alloantibodies were detected using the MAIPA method. Both children were transfused with compatible HPA-3bb platelets and perfused with intravenous immunoglobulins associated with corticoids. Conclusions This case shows that anti- HPA-3 maternal alloimmunization is a potentially devastating disease. The detection of anti- HPA-3 alloantibodies may be a challenge for platelet immunologists to ascertain the diagnosis. In case of bleeding, platelet transfusion is the therapy to be used in an emergency. For subsequent pregnancies, the mother should be followed up in a referral centre and antenatal management may be proposed. [ABSTRACT FROM AUTHOR]

Human platelet antigens (HPAs) and their respective antibodies are responsible for different clinical conditions of alloimmune-mediated thrombocytopenia. More recently, the involvement of HPA antibodies in rejection reactions to transplantation has been suggested. The detection of the causative HPA antibodies is therefore essential for the diagnosis and the implementation of preventive and therapeutic strategies. However, none of the available methods alone is presently able to detect all clinically relevant antibodies. In this review, we describe the old and new methods available for the detection of HPA antibodies, and discuss on their advantages and disadvantages. [ABSTRACT FROM AUTHOR]

SUMMARY Objective To prevent neonatal alloimmune thrombocytopenia due to anti-group A antibody perinatal management was performed. Background We previously reported a case of severe intracranial haemorrhage associated with neonatal alloimmune thrombocytopenia due to anti-group A isoantibody. Material/Methods A 40-year-old Japanese woman, gravida 4 para 1, was pregnant with her second baby. The previous sibling developed severe thrombocytopenia and died 10 days after birth due to intracranial haemorrhage. He was diagnosed with neonatal alloimmune thrombocytopenia; the causative antibody was found to be the anti-group A antibody. Prednisone was started at 7 weeks' gestational age. Intravenous immunoglobulin 1 g kg−1 week−1 was started at 29 weeks' gestational age and continued to delivery. Serological studies and genotyping were performed. Results The second boy was delivered at 33 weeks' gestational age by caesarean section. He was discharged without intracranial haemorrhage or thrombocytopenia. The anti-group A antibody titre in the maternal serum was 2048-4096 (normal range: 4-64). The anti-group A antibody titre in the newborn's serum was 4. Cross-matching between the maternal serum and the paternal platelets was positive. Conclusion Owing to the history of neonatal alloimmune thrombocytopenia causing intracranial haemorrhage and death of the previous sibling, strict follow-up of the subsequent pregnancy was conducted. [ABSTRACT FROM AUTHOR]

To date, 33 human platelet alloantigens ( HPAs) have been identified on six functionally important platelet glycoprotein ( GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia ( FNAIT), posttransfusion purpura ( PTP) and multitransfusion platelet refractoriness ( MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/ IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA-1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/ IX, GPIa/ IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic 'systems' where the -a form designates the higher frequency allele and the -b form, the lower. Twenty-one other HPAs are low-frequency or rare antigens for which postulated higher frequency -a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen ( HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR. [ABSTRACT FROM AUTHOR]

Fetal neonatal alloimmune thrombocytopenia ( FNAIT) is a devastating bleeding disorder in the fetus or neonate caused by transplacental transport of maternal alloantibodies to paternal-derived antigen on fetal platelets. In Caucasians, up to 80% of FNAIT cases result from maternal immunization to human platelet antigen ( HPA)-1a. New methods have developed facilitating detection of common and private antibodies against HPAs triggering FNAIT. Understanding the pathogenesis of FNAIT made it possible to develop a novel strategy to treat this disorder. To date, recombinant monoclonal antibodies directed against the β3 integrin and Fc receptors have been tested in a mouse model of FNAIT, and seem to be promising. Whether those novel treatments will eventually replace the conventional high dose immunoglobulin G in women with FNAIT is yet unknown. [ABSTRACT FROM AUTHOR]

The article discusses the implications of genetic polymorphisms of human platelet antigens (HPA) in Asian population in the establisment of blood platelet donor registries. It states that HPA antigen causes the development of HPA alloantibodies implicated in platelet immune disorders including fetal and neonatal alloimmune thrombocytopenia, post-transfusion purpura, and multiple platelet transfusion refractoriness. The importance of HPA genotyping in developing platelet donor register is noted.

Neonatal alloimmune thrombocytopenia (NAIT), with an incidence of one in 1000 live births, is the most common cause of severe thrombocytopenia and intra-cerebral haemorrhage in term neonates. NAIT results from trans-placental passage of maternal antibodies against a paternally derived fetal platelet alloantigen. Clinical presentation varies from unexpected thrombocytopenia on a blood film in a well newborn to intracranial haemorrhage (ICH). In contrast to haemolytic disease of the newborn, NAIT can present in a first pregnancy, and subsequent pregnancies are usually more severely affected. The role of antenatal screening for maternal alloantibodies instead of fetal blood sampling to identify at-risk fetuses remains uncertain, but there is a trend towards less invasive maternally directed treatment for at-risk pregnancies. Neonatal management is aimed at preventing or limiting thrombocytopenic bleeding with transfusion of antigen-matched platelets. [ABSTRACT FROM AUTHOR]

Pregnancy may allow alloimmunization against human platelet antigens (HPA), which can lead to neonatal alloimmune thrombocytopenia (NAIT). The specificities of alloantibodies are closely related to the distribution of the HPA systems. A total of 281 Tunisian multiparous women (mean number of pregnancies: 4.5) were phenotyped for the HPA-1, -3 and -5 systems, by monoclonal antibody immobilization of platelet antigens (MAIPA). We searched for antibodies against HPA-1a, HPA-3a, HPA-5b and HPA-5a in HPA-1b1b, HPA-3b3b, HPA-5a5a and HPA-5b5b individuals, respectively. The gene frequencies were: 0·83 for HPA-1a, 0·17 for HPA-1b, 0·78 for HPA-3a, 0·22 for HPA-3b, 0·82 for HPA-5a and 0·18 for HPA-5b. Anti-HPA-5b antibodies were present in eight sera and anti-HPA-3a antibodies were present in one serum. The anti-HPA-5b system is the most frequently involved in platelet alloimmunization in Tunisian multiparous women. However, prospective trials are required to confirm this result and to determine the exact frequencies and clinical relevance of platelet alloantibodies in pregnant Tunisian women. [ABSTRACT FROM AUTHOR]

The implementation of an antenatal screening programme for neonatal alloimmune thrombocytopenia (NAIT) is currently under debate. We evaluated the detection rate for NAIT in a nonscreened population of 661 200 births where NAIT was diagnosed on clinical indication. We did a cross-sectional comparison with a population of 100 448 human platelet antigen 1a (HPA1a)-screened pregnancies from three of the five health regions in Norway. In a nonscreening situation, 7.5 cases of NAIT were detected per year compared with 53 cases when screening was applied. The detection rate of NAIT in Norway was therefore 14% of the expected rate. [ABSTRACT FROM AUTHOR]

Neonatal alloimmune thrombocytopenia (NAIT) occurs because of transplacentally acquired maternal platelet alloantibodies. Most of the alloantibodies are against human platelet antigens, but the alloantibody against CD36 is rare. A full-term female baby was delivered by a mother who experienced two spontaneous abortions. The baby had thrombocytopenia with cephalhematoma. The platelet count increased by immunoglobulin therapy (400 mg/kg) for 3 d. Platelet antibody was detected in the postpartum maternal serum. The specificity of the antibody directed against platelets was identified as anti-Naka (CD36). Flow cytometric analysis showed no expression of CD36 in both platelets and monocytes from mother. Mutation analysis revealed two different splicing isoforms of maternal CD36 mRNA. One allele was exon 4 skipping, another was exon 9 skipping, both of which led to a frameshift and produced a truncated CD36 protein. These results indicate that NAIT is caused by maternal CD36 deficiency having CD36 splicing abnormalities. [ABSTRACT FROM AUTHOR]

Problem Lymphocyte immunotherapy (LIT) is applied in infertility treatment. Moreover, it has been suggested for prevention of rhesus D-hemolytic disease and as a vaccine for reduction of human immunodeficiency virus-1 susceptibility. Although transfusion-related problems have been rarely reported they were a matter of debate. Here we discuss extensive single-center experience with intradermal LIT for implantation failure and recurrent miscarriages. Method of study Retrospective 2- to 3-year follow-up of in vitro fertilization couples treated during 1996–2002 (feedback 2848/3041 = 93%), registering 930 deliveries. Prospective survey for acute reactions for 2000–2003 (feedback 2687/3246 = 83%). Review of the literature. Results Infections of the patient and transplant rejection later in life are minor residual risks. Post-transfusion purpura was suspected once but not verified. Anaphylaxis or malignancy were not promoted. Fetal/newborn alloimmune disease (severe hemolytic disease, thrombocytopenia, neutropenia) were not observed. Conclusion Based on microbiological, immunological, and hematological testing the risks of intradermal LIT are low. [ABSTRACT FROM AUTHOR]

Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies to antigens presented on foetal platelets cause their immune destruction. Whether human leucocyte antigen (HLA) antibodies can cause NAIT is controversial. Here, a patient was described who suffered from a NAIT caused by an HLA-B27 antibody. Sera from the mother and the newborn were tested for human platelet antigen antibodies and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phase-linked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis. No antibodies against cluster designation (CD)109 and platelet glycoproteins of the father were found in patient's and mother's serum. However, HLA ELISA was used to identify HLA antibody in both sera. The antibody was specified as HLA-B27 antibody. Typing results showed that the father descended HLA-B27 antigen on patient and his brother. The mother was HLA-B27 negative. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-B27 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented. [ABSTRACT FROM AUTHOR]

Background and Objectives Platelet-specific antibodies are detectable in only about 30% in suspected neonatal alloimmune thrombocytopenia (NAIT). Human leucocyte antigen (HLA) class I antibodies are often detectable, and as platelets express the corresponding antigens, it has been suggested that these antibodies can be responsible for NAIT. Light chain phenotyping may assist in the diagnosis of HLA antibodies-induced NAIT. Materials and Methods We determined light chain phenotypes of platelet reactive HLA antibodies in 17 sera from mothers who delivered offspring with suspected NAIT. Ten sera also contained platelet-specific antibodies: HPA-1a ( n = 5, one with HPA-15b), HPA-5b ( n = 4) and autoantibodies ( n = 1). Sera were tested for kappa or lambda restriction by monoclonal antibody-specific immobilization of platelet antigens (MAIPA). Results The cross-match with paternal platelets was positive in all cases due to HLA antibodies. We identified 5, 3 and 3 sera to contain lymphocytotoxic antibodies of single, two or multiple specificities, respectively. In six cases, HLA antibodies were only detectable by MAIPA. Light chain restriction ( n = 9) was not associated with HPA containing antibodies or to any pattern of the HLA antibodies. Similarly, polyclonal antibodies ( n = 8) were seen in all categories. Conclusion We show that pregnancy-associated HLA antibodies can be clonal or polyclonal, irrespective of a diagnosis of NAIT. One-sentence summary Pregnancy associated HLA antibodies can be clonal or polyclonal, irrespective a diagnosis of NAIT. [ABSTRACT FROM AUTHOR]

Serological evaluation of maternal sera for platelet antibodies in suspected fetal/neonatal alloimmune thrombocytopenia (FNAITP) discloses in only≈ 30% of individuals a platelet-specific antibody. Transfusion-induced alloimmunization against human platelet antigen-15 (HPA-15) has been reported to be about as common as against HPA-5, the second most common platelet antibody. Thus, anti-HPA-15 may also contribute significantly to yet-unclear cases of FNAITP.In this retrospective analysis, we provide data on maternal platelet antibodies from 309 mothers who delivered an offspring with suspected FNAITP.Genotyping maternal and paternal samples (togethern = 573) revealed a gene frequency of 0·496 for HPA-15a and a gene frequency of 0·504 for HPA-15b. HPA-15 antibodies were detected in 2% of all samples. Anti-HPA-15a and -15b were detected in two and three samples, respectively. One serum reacted equally with HPA-15a and -15b platelets. The most frequent platelet-specific antibodies were anti-HPA-1a (22%), but anti-HPA-5b (8·4%) were more frequent than anti-HPA-15. In addition, panreactive (5·5%) or autoreactive (5·2%) anti-GPIIb/IIIa or anti-GPIb/IX were detectable in maternal samples.These data indicate that HPA-15 alloimmunization needs only to be considered in subjects with suspected FNAITP if no other platelet-specific antibody is detectable. The presence of panreactive or autoreactive antibodies should also be considered in neonatal thrombocytopenia. [ABSTRACT FROM AUTHOR]

Marín L, Torío A, Muro M, Fernandez-Parra R, Minguela A, Bosch V, Alvarez-López MR, García-Alonso AM. Alloimmune neonatal neutropenia and thrombocytopenia associated with maternal anti HNA-1a, HPA-3b and HLA antibodies.Pediatr Allergy Immunol 2005.© 2005 Blackwell MunksgaardThe incidence of alloimmune neonatal neutropenia combined with neonatal alloimmune thrombocytopenia is very low. We report a case of a neonate who suffered severe neutropenia and thombocytopenia with widespread petechial spots. The presence of alloantibodies in mother's and patient's sera was analyzed by lymphocytotoxicity test, agglutination test, granulocyte indirect immunofluorescence test, platelet immunofluorescence test (PIFT) and solid phase enzyme-linked immunosorbent assay. Human neutrophil antigens (HNA) andhuman platelet antigen (HPA) genotypes were tested by polymerase chain reaction analyses. The mother's and patient's sera reacted with neutrophils and lymphocytes of the father. PIFT revealed the presence of IgG anti-platelet antibodies in the patient's serum but the test was negative in the maternal serum. Analyses of HNA-1 and HPA genotypes of the family revealed maternal-neonatal HNA-1a and HPA-3b mismatch. The study of the mother's and patient's sera showed the presence of anti HNA1a, HPA-3b and HLA antibodies specific for HLA-A3 and HLA-B38 antigens. These results suggest that the transplacental passage of maternal HNA-1a, HPA-3b and HLA alloantibodies caused neutropenia and thrombocytopenia in this patient. [ABSTRACT FROM AUTHOR]

We report the second case of neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-3b (Bakb) antibody. The infant was severely affected with intracranial haemorrhage. Most importantly, we were able to detect this antibody only by using fresh, unfixed platelets as antigen. This antibody was detectable neither by conventional mixed passive haemagglutination, platelet immunofluorescence test using fixed platelets, nor by monoclonal antigen immobilization of platelet antigen assay using solubilized platelets. We assume that this antibody reacts only with fresh platelets and that the antigen is a labile component of HPA-3b (Bakb). [ABSTRACT FROM AUTHOR]

We report the second case of neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-3b (Bakb) antibody. The infant was severely affected with intracranial haemorrhage. Most importantly, we were able to detect this antibody only by using fresh, unfixed platelets as antigen. This antibody was detectable neither by conventional mixed passive haemagglutination, platelet immunofluorescence test using fixed platelets, nor by monoclonal antigen immobilization of platelet antigen assay using solubilized platelets. We assume that this antibody reacts only with fresh platelets and that the antigen is a labile component of HPA-3b (Bakb). [ABSTRACT FROM AUTHOR]

Background and Objectives Intracranial haemorrhage (ICH) of the fetus or newborn is a severe complication of fetal or neonatal alloimmune thrombocytopenia (FNAIT). In order to attain management decisions to prevent ICH, the risk of ICH in successive pregnancies with thrombocytopenia, with or without a history of ICH, must be established. Materials and Methods We performed a search of medline for ICH cases in untreated FNAIT pregnancies. After exclusion of cases with confounding factors, 24 reports, describing 62 pregnancies of 27 mothers, were eligible. In addition, two mothers with five pregnancies were included from our own case records. Observational studies were examined to estimate the risk of ICH in subsequent FNAIT pregnancies without a history of ICH. Finally, medline was searched for complication rates in the treatment of FNAIT pregnancies. Results In 52% of the ICH cases, a previous sibling suffered from ICH. The recurrence rate of ICH in the subsequent offspring of women with a history of FNAIT with ICH was 72%[confidence interval (CI): 46–98%] without inclusion of fetal deaths and 79% (CI: 61–97%) with inclusion of fetal deaths. In 48% of the ICH cases, the previous sibling had thrombocytopenia but not ICH. Population studies revealed an overall ICH risk in thrombocytopenic infants of 11% (CI: 0·8–23%) without inclusion of fetal deaths and 15% (CI: 1·5–19%) with inclusion of fetal deaths. Assuming occurrence in 48%, the risk of ICH in a subsequent pregnancy following a history of FNAIT without ICH, was estimated to be 7% (CI: 0·5–13%). Invasive treatment strategies carry a risk of 2·8% (CI: 1·2–4·4%) on complications. Conclusions The number of eligible publications on ICH in untreated FNAIT pregnancies is strikingly limited. The recurrence rate is high. As sufficient data on successive FNAIT cases without ICH are lacking, the occurrence of ICH in pregnancies with thrombocytopenia, but without ICH in a previous sibling, cannot be predicted. We estimate this risk to be 7%. This risk must be balanced against the risk of interventions in treatment strategies. [ABSTRACT FROM AUTHOR]

Neonatal alloimmune thrombocytopenia (NAIT) can occur when a mother is immunized against fetal platelet antigens inherited from the father. Early diagnosis and appropriate platelet transfusion therapy are essential to prevent life-threatening intracranial hemorrhage in the thrombocytopenic fetus or neonate. Five major human platelet antigen (HPA) systems are capable of causing this disorder with HPA-1a indicated most frequently. This article reviews the pathophysiology, clinical aspects, and management of NAIT. We also present our experience with treatment of neonates affected with this disorder. [ABSTRACT FROM AUTHOR]

Anti-HPA-5b is the most commonly found platelet-specific antibody among pregnant women, but it does not cause severe fetal–neonatal alloimmune thrombocytopenia in the majority of affected infants. However, as the sequelae of the affected children may become severe, it is necessary to identify the risk factors for neonatal alloimmune thrombocytopenia. Of 21 354 consecutive pregnant women, 138 [0·65%; 95% confidence interval (CI) 0·54–0·75%], corresponding to 13·2% of the 1049 HPA-5b- women caculated by the gene frequency, were positive for anti-HPA-5b at the first trimester. Anti-HPA-5b was titrated in specimens obtained at the third trimester and antibody-positive women and their neonates were HPA-5 genotyped. Platelet counts in cord blood and 3 d after birth were assessed in the infants born to these mothers. Chi-square analysis showed no significant relationship between the titres of maternal antibody to HPA-5b and the number of pregnancies. There was a significant difference in platelet counts at d 3 between neonates who were compatible (267 × 109/l) or incompatible (220 × 109/l, P < 0·05) with maternal anti-HPA-5b. HPA-5b antibody titres ≥ 64 were related to the development of thrombocytopenia (< 150 × 109/l) in neonates 1 d and 3 d after birth. A high titre (≥ 64) had a positive predictive value of 50% for thrombocytopenia 3 d after birth when the infant was HPA-5b+ and a negative predictive value of 100%. These results indicate that a high titre (≥ 64) of anti-HPA-5b is associated with a higher risk of neonatal thrombocytopenia, even if anti-HPA-5b-induced severe thrombocytopenia rarely develops. [ABSTRACT FROM AUTHOR]

Neonatal alloimmune thrombocytopenia (NAIT) occurs as a result of maternal alloimmunization against paternally inherited antigens on foetal platelets. Platelets express platelet specific antigens (HPA) along with human leucocyte antigens (HLA) class I. Although anti-HLA class I antibodies are often detectable in pregnant women, their role in NAIT is considered controversial. We report a case of NAIT where the most sensitive serological analysis and molecular methods could not detect platelet specific antibodies. Only HLA incompatibility and presence of anti-HLA-A24 antibodies in both the mother’s and the newborn’s serum were proven. Conclusion: This case supports the idea that some anti-HLA class I antibodies could cause NAIT. [ABSTRACT FROM AUTHOR]

The article presents a case study of a woman giving birth to a baby girl in Japan which has neonatal thrombocytopenia caused by anti-human platelet anitgen-5a. The baby weighed 2920 grams and has an Apgar score of 9/10. The article discusses immunoglobulin administration, intracranial hemorrhage cases, and fetal management.