Identification and follow-up of pregnant women with platelet-type human platelet antigen (HPA)-1bb alloimmunized with fetal HPA-1a (original) (raw)
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Maternal alloimmunization against fetal platelet antigens: a prospective study
British Journal of Haematology, 1995
Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies to fetal platelet antigens. This prospective study was carried out to evaluate the incidence of anti-platelet antibodies in 933 mother-child pairs where the mother and child were typed for the human platelet antigens (HPA)-1,-2,-3,-5. Sera from mismatched mother-child pairs were screened for anti-platelet antibodies, anti-HLA class I and blood group ABO IgG antibodies. Platelet-specific antibodies were anti-HPA-3a in one and anti-HPA-5b in 1 7 neonates, respectively. All these neonates had normal platelet counts. One woman had autoreactive antibodies. Anti-HLA class I and anti-blood group A IgC antibodies were detected in five and four neonates, respectively, born with a platelet count < 150 x 109/1. None of the 11 homozygous HPA-lb mothers became immunized against their heterozygous offspring. The maternal HLA-allotypes HLA-DR52 and-DR6, typically found in individuals immunized against HPA-la and-5b, respectively, were found in three of 11 HPA-b/b nonresponders and eight of the anti-HPA-5b responders. The results indicate that a risk for NAIT due to HPA-2 and-3 alloimmunization is low. The HLA allotypes do not predict the risk for NAIT due to HPA-1 or-5 alloimmunization. Maternal anti-HPA-5b antibodies do not correlate with the platelet count in the neonate.
The natural history of maternal immunization against foetal platelet alloantigens
Transfusion Medicine, 2004
Foetomaternal alloimmune thrombocytopenia (FMAIT) occurs when maternal antibodies of an antigen-negative mother cause destruction of sensitized foetal platelets. In Caucasian populations, 6-12% of human platelet antigen (HPA)-1a-negative women develop anti-HPA-1a, and the incidence of clinically affected cases is estimated to be 10-20% of immunized women. This study was performed in order to elucidate the rate of maternal immunization, incidence of FMAIT and the likely outcome of the condition in Asians. Excluding two or more pregnancies during the period, serum samples from 24 630 pregnant women, mainly Japanese, were screened for antibodies against platelet alloantigens by means of mixed passive haemagglutination (MPHA) (Anti-HPA-MPHA, Olympus, Tokyo). Antibodies were detected in 0Á91% (223/24 630) of the women's samples and the immunization rate was correlated with the number of pregnancies. Antibody specificity included anti-HPA-4b (49), anti-HPA-5a (three), anti-HPA-5b (168), anti-HPA-4b þ 5b (one) and anti-Nak a (CD36) (two). No alloimmunization was observed within the HPA-1, HPA-2, HPA-3 or HPA-6 systems. Among HPA-4b-or HPA-5b-negative women, 24% or 14% estimated, respectively, had antibodies and 26% (10/38) or 10% (12/ 125) of neonates, respectively, born to these mothers developed thrombocytopenia. Two neonates born to mothers having anti-HPA-4b developed generalized purpura. No cases of intracranial bleeding or death due to FMAIT were recorded. Generalized purpura due to FMAIT occurs in one in 9359 (95% CI: 1 in 77 519-1 in 2591) pregnancies solely because of HPA-4b incompatibility.
BJOG: An International Journal of Obstetrics and Gynaecology, 2003
Objective Fetomaternal mismatch for human platelet antigen (HPA)-1a accounts for approximately 85% of cases of neonatal alloimmune thrombocytopenia. The purpose of the study was to determine the prevalence of the HPA-1a negative platelet phenotype in a cohort of pregnant women in Ireland, the rate of alloimmunisation to HPA-1a in HPA-1 mismatched pregnancies and the associated incidence of neonatal alloimmune thrombocytopenia. Design A prospective case -control study.
Vox Sanguinis, 2005
Background and Objectives 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. Materials and Methods In this retrospective analysis, we provide data on maternal platelet antibodies from 309 mothers who delivered an offspring with suspected FNAITP. Results Genotyping maternal and paternal samples (together n = 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. Conclusions 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.
PLOS ONE
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that may cause severe bleeding complications with risk of perinatal death or lifelong disability. The main cause of FNAIT is maternal antibodies against human platelet antigen (HPA)-1a. Both fetomaternal bleeding and transplacental trafficking of fetal cells during pregnancy could be the cause of alloimmunization. Persistence of fetal cells in the mother (fetal microchimerism) and maternal cells in the child (maternal microchimerism) are well-recognized phenomena. Thus, it could be envisaged that fetal exposure to the HPA-1a antigen could tolerize an HPA-1a negative female fetus and prevent production of anti-HPA-1a antibodies later in life if she becomes pregnant with an HPA-1a positive fetus. The objective of the current study was to assess if the risk of producing anti-HPA-1a antibodies and the severity of neonatal thrombocytopenia in HPA-1a negative women with HPA-1a positive mothers (i.e. the mother is HPA-1a/b), was lower than in HPA-1a negative women with HPA-1a negative mothers. HPA-1a negative women with HPA-1a antibodies, identified from a Norwegian screening study (1996-2004), where HPA-1 genotype of their mothers was available, were included in the study. The frequency of HPA-1a positive mothers to HPA-1a immunized daughters were compared to the calculated frequency in the general population. We did not find any difference in the frequency of HPA-1ab among mothers to daughters with HPA-1a antibodies as compared with the general population. Furthermore, acknowledging samplesize limitations, we neither found an association between the mothers' HPA type and their daughters' anti-HPA-1a antibody levels or any difference between the two groups of mothers (HPA-1ab vs HPA-1bb), with respect to frequency of thrombocytopenia in the children of their daughters with HPA-1a antibodies. Hence, there was no indication of tolerance against fetal HPA-1a antigen in HPA-1bb women who had been exposed to HPA-1a antigen during fetal development.
…, 2008
Background Neonatal alloimmune thrombocytopenia is most commonly due to transplacental passage of maternal anti-HPA 1a antibodies. A prospective study was carried out to evaluate the pattern and quantity of maternal anti-HPA 1a antibodies in order to predict the level of thrombocytopenia in the neonates. Design and Methods A monoclonal antibody immobilization of platelet antigen assay was used to detect antibodies in maternal samples from 1,990 HPA 1bb women. HLA DRB3*0101 typing was performed in all immunized women by sequencing the HLA DRB3 gene when present. Results Primary immunization more often took place in connection with delivery than during the first pregnancy. There was a strong correlation between maternal antibody levels and the platelet counts in the newborn (R 2 =0.49, p<0.001). A maternal antibody level above 3.0 IU/mL measured in gestational week 22 or 34 had a diagnostic sensitivity and specificity of 93% and 63%, respectively, for predicting the grade of neonatal thrombocytopenia. The women who were negative for HLA DRB3*0101 had significantly lower anti-HPA 1a antibody levels than those who were HLA DRB3*0101 positive (p<0.007). In contrast to primigravida, in whom anti-HPA 1a antibody levels increased during pregnancy, the antibody level decreased in 92 of 147 women who had been pregnant previously (P92 or more of 147 = 0.003). The anti-HPA 1a antibody level regularly increased after delivery. Conclusions Maternal anti-HPA 1a antibody levels in weeks 22 and 34 of pregnancy are good predictors of the degree of thrombocytopenia in the newborn both in the first and subsequent pregnancies. Most mothers became immunized at the time of delivery.
Platelet-specific alloantigens and antibodies in Tunisian women after three or more pregnancies
Transfusion Medicine, 2009
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.
Transfusion, 2018
The development of new noninvasive approaches for the diagnosis of human platelet antigen (HPA)-1 fetomaternal incompatibility has become of great interest. These approaches allow determination of whether the fetus is incompatible or not with the mother and a decision on antenatal therapy to avoid fetal or neonatal alloimmune thrombocytopenia (FNAIT). The objective of this work was to perform rapid, noninvasive prenatal test for HPA-1ab fetal antigen detection after the detection of an HPA-1-homozygous mother by using plasma cell-free DNA (cfDNA). The HPA-1 genotypes of 142 pregnant women and 17 nonpregnant controls were retrospectively determined by high-resolution melting (HRM) polymerase chain reaction (PCR). Coamplification at lower denaturation temperature (COLD) HRM PCR was performed to determine the fetal genotype analyzing cfDNA from all HPA-1bb pregnant women. After the HRM analysis, the following genotypes were identified: HPA-1aa (71.13%), HPA-1bb (2.8%), and HPA-1ab (26....
Archives of Gynecology and Obstetrics, 2010
Introduction Maternal-fetal alloimmune thrombocytopenia complicates about 0.1% of all pregnancies and is associated with major fetal and neonatal morbidity and mortality, especially spontaneous central nervous system bleeding leading to death and neurological handicaps. Successful prevention and treatment depend on the identiWcation of at-risk possible carriers of anti-platelet antibodies. Case report We report a case of a mother with a previous child that developed neonatal hemorrhage; HPA-5b antiplatelet antibodies were detected post-natally. During the next pregnancy, fetal genotyping conWrmed the presence of HPA-5b antigen; she was treated with weekly intravenous human immunoglobulin and oral prednisone. Pregnancy evolved without remarkable features and a full-term baby was delivered, with normal platelet counts. Conclusion Fetal alloimmune thrombocytopenia is a potentially lethal condition, but early detection and prevention lead to successful outcome in most cases.