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Background: Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) results from maternal platelet alloimmunization against paternal antigens inherited by the fetus, most often due to the Human Platelet Antigen (HPA)‐1 system in Caucasians. We investigated in 2023, a 30‐year‐old Caucasian woman Gravida 2 Para 1 who gave birth at 35 weeks of gestation to a male (body weight 2210 g) without signs of bleeding. A severe thrombocytopenia (platelet count at 3 G/L) was discovered incidentally a few hours after delivery in the context of the management of a respiratory distress. The newborn recovered after one platelet concentrate transfusion and normalized his platelet count at Day 5. Study Design and Methods: FNAIT investigation was performed according to guideline recommendations. Platelet genotyping was carried out by multiplex PCR. Maternal serological investigation included Monoclonal Antibody‐specific Immobilization of Platelet Antigens method (MAIPA) and Luminex technology. Results: Parental and newborn genotyping pointed out an HPA‐4 incompatibility between the mother and the newborn and the father. Serological investigation revealed an anti‐HPA‐4b alloantibody confirming the diagnosis of neonatal alloimmune thrombocytopenia. Conclusion: We described the third case of anti‐HPA‐4b alloantibody discovered in a Caucasian mother. This case strengthens the need for reference laboratory to genotype a panel of HPA alleles reflecting local genetic population diversity and for crossmatch of maternal serum with fresh paternal platelets in clinical suspected cases of neonatal alloimmune thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background and Objectives: Detection of anti‐platelet antibodies is required for the diagnosis of foetal/neonatal alloimmune thrombocytopaenia. The most commonly used methods for anti‐platelet antibody detection are the monoclonal antibody‐specific immobilization of platelet antigens (MAIPA) and the Luminex bead assay (PakLx). However, for economic reasons, the use of the PakLx assay is limited. Materials and Methods: In the present study, we evaluated the performance of an optimized protocol based on a half‐volume of PakLx reagents. We compared two alternative procedures: one with a half‐volume of all components including patient samples, and another based on a half‐volume of reagents but a standard volume of patient sample. Results: Our results obtained with a panel of 67 samples demonstrate improved sensitivity when using a standard sample volume. Conclusion: In the event of an inconclusive result with this optimized protocol (e.g., incomplete panel of positive Luminex beads), we recommend testing the sample with an alternative protocol (e.g., MAIPA or the original PakLx protocol). [ABSTRACT FROM AUTHOR]

Platelet compatible transfusion can effectively solve the immune mediated platelet transfusion refractoriness (PTR), save platelet resources and improve blood safety. This paper comments and prospects the compatibility modes of HLA, HPA and CD36, HLA antibody titer, antigen immunogenicity and the development of platelet compatible transfusion. The pattern of HLA compatible platelets involves the matching in the alleles, antigens and epitopes levels, respectively, as well as avoidance donor specificity antibody (DSA) method. While setting the mean fluorescence intensity (MFI) threshold of avoidance DSA needs to be explored when using the DSA prediction method. Allele specific HLA antibodies can be found in the patients with PTR. Therefore, the patients and donors should be genotyped for HLA-A, -B loci at high-resolution level in order to avoid allele specific HLA antibodies. The immunogenicity of various antigens or epitopes at HLA-A and -B loci are different. Selecting donor platelets with low antigen expression or low immunogenicity may be a way of HLA compatible platelets. As the probability and type of HPA antibody production are different in the various populations, the approaching of compatibility HPA involves allele matching and avoidance DSA. As to CD36, the compatibility mode mainly refers to avoidance DSA, which means blood donors with CD36 antigen type Ⅰdeficiency are preferentially selected, and then those with CD36 antigen type Ⅱ deficiency. In the future, more attention should be paid to the scale up of database capacity and update of the information construction. The time waiting for compatible platelets transfusion in clinical could be significantly shortened if the requiring and matching are only conducted within the inventory and candidate platelets.

Background Human platelet antigens (HPAs) are alloantigens for antiplatelet alloantibodies and associated with the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins. Methods We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls including HPA data of 998 Taiwanese blood donors. We analyzed HPA allele frequencies including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia. Results In the whole ITP cohort, HPA2ab predicted a low platelet count. HPA2b was associated with the risk of developing ITP, but not with anti-GPIb/IX antibodies. HPA15b was correlated with multiple antiplatelet antibodies. In the primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M. In contrast, in the HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies, HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA caomparred with those without anti-GPIIb/IIIa antibodies. Similar to the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, especially cryoglobulin IgA. Furthermore, cryoglobulins in the HCV-ITP patients showed characteristics to antiplatelet antibodies. Conclusion HPA alleles were associated with antiplatelet autoantibodies but had different impacts in the patients with primary ITP and HCV-ITP. The pathophysiology and characteristics of antiplatelet antibodies were different between these two groups. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in the HCV patients.

The detection of the most significant erythrocyte antigens present in each one of the individuals is fundamental when carrying out a transfusion or a transplant. Detection to date is performed by conventional serological methods through the antigen-antibody reaction. But several drawbacks may arise depending on the pathology under study, limiting the availability of blood components. Molecular methods such as genotyping is a tool that complements sensitivity and specificity and has come to revolutionize immunohematology in the blood bank, allowing not only the detection of erythrocyte antigens but also platelet antigens. These methodologies are applicable in patients and in large-scale donors, starting from the allelic variants present in each of the genes that code for the antigens of clinical interest, using microarray systems or systems based on particles labeled with specific probes or their variants that allow an analysis from the immunohematological point of view. [ABSTRACT FROM AUTHOR]

Objective To explore the polymorphism of HPA-1-6w, HPA-15 and 32bw-35bw in platelet donors in Deyang, Sichuan, and estimate whether to include the detection of 32bw-35bw in the platelet bank. Methods Polymerase chain reaction with sequenced based typing (PCR-SBT) was used to sequence the HPA-1-6w, HPA-15 and 32bw-35bw loci of 205 platelet donors in Deyang. Allele frequencies were calculated by the direct counting method. The frequencies of HPA-1-6 and 15 alleles in northern and southern Chinese, Japanese and Australian population were compared, and those HPA loci and HPA-32bw-35bw were searched in the Chinese Millionome Database (CMDB) and genomAD to obtain the polymorphism data. Then the Chi-square test was performed with the data of this study through GraphPad Prism 9 software. Results The allele frequencies of HPA-1b, 2b, 3b, 5b, 6bw and HPA-15b were 0.005(2/410), 0.037(15/410), 0.471(193/410), 0.020(8/410), 0.010(4/410) and 0.461(189/410), respectively, b allele of HPA-32bw-35bw and HPA-4 was not detected. Statistical significance was observed between the HPA-1b allele frequency of this study and northern Chinese, Australian population and genomAD global population sample (P< 0.05, 0.005 vs 0.014 vs 0.145 vs 0.122). The frequency of HPA-2b alleles in this study, Japanese population and genomAD global population samples was 0.037 vs 0.120 vs 0.100, with statistical difference(P

Background: Due to the presence of platelet antigen polymorphisms, human platelet membrane glycoproteins can be identified as an alloantigen or autoantigen. The aim of this study was to determine the frequencies of human platelet antigens (HPAs)-1 to-5 and-15 in Turkmen blood donors and establish a panel of accredited HPAs negative donors as well as an HPA-typed platelet donor registry. Materials and Methods: HPA-1 to-5 and-15 typing was performed by the polymerase chain reaction-sequence-specific primer techniques on 80 unrelated Turkmen donors who were referred to Aq-Qala Blood Transfusion Center in Golestan Province from September 2018 to October 2019. Results: The frequencies of HPA phenotypes were determined as follows: HPA-1aa: 92.5%, HPA-1ab: 7.5%, HPA-2aa: 77.5%, HPA-2ab: 20.0%, HPA-2bb: 2.5%, HPA-3aa: 75.3%, HPA-3ab: 50%, HPA-3bb: 11.2%, HPA-4aa: 100%, HPA-5aa: 78.5%, HPA-5ab: 21.5%, HPA-15aa: 41.2%, HPA-15ab: 56.2% and HPA-15bb: 17.5%. Conclusion: Determining the genotype of HPAs that play an important role in platelet refractory can improve the management of alloimmunization due to the incompatibility of HPAs between the recipients and donors. Therefore, the registration process for national platelet donors can help patients accelerate and improve the quality of transfused platelets.

Summary: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloantibodies directed against the human platelet antigens (mostly HPA‐1a or HPA‐5b) of the (unborn) child and can lead to severe bleeding. Anti‐HPA‐1a‐mediated FNAIT shows a severe clinical outcome more often than anti‐HPA‐5b‐mediated FNAIT. Given the relatively high prevalence of anti‐HPA‐5b in pregnant women, the detection of anti‐HPA‐5b in FNAIT‐suspected cases may in some cases be an incidental finding. Therefore we investigated the frequency of anti‐HPA‐5b‐associated severe bleeding in FNAIT. We performed a retrospective nationwide cohort study in cases with clinical suspicion of FNAIT. HPA antibody screening was performed using monoclonal antibody‐specific immobilisation of platelet antigens. Parents and neonates were typed for the cognate antigen. Clinical data were collected by a structured questionnaire. In 1 864 suspected FNAIT cases, 161 cases (8·6%) had anti‐HPA‐1a and 60 (3·2%) had anti‐HPA‐5b. The proportion of cases with severe bleeding did not differ between the cases with anti‐HPA‐1a (14/129; 11%) and anti‐HPA‐5b (4/40; 10%). In multigravida pregnant women with a FNAIT‐suspected child, 100% (81/81) of anti‐HPA‐1a cases and 79% (38/48) of anti‐HPA‐5b cases were HPA‐incompatible, whereas 86% and 52% respectively were expected, based on the HPA allele distribution. We conclude that anti‐HPA‐5b can be associated with severe neonatal bleeding symptoms. A prospective study is needed for true assessment of the natural history of anti‐HPA‐5b mediated FNAIT. [ABSTRACT FROM AUTHOR]

Introduction: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an uncommon condition due to maternal alloimmunization of fetal platelet leading to thrombocytopenia in fetal and neonate. Our study determine the incidence, common platelet alloantibodies and the associated maternal and neonatal factors of FNAIT in Malaysia. Methods: Matched case control study of FNAIT and control (39 FNAIT cases and 39 randomly selected controls) through retrospective record review from the year 2011 to 2019 was performed at National Blood Centre, Malaysia. Data were analysed using Statistical Package for Social Sciences (SPSS) version 26.0. Differences between cases and controls were evaluated using chi-square test for categorical variables and t-test or Mann-Whitney test for normally and non-normally distributed variables. Results: The incidence of FNAIT in Malaysia was 0.85 per 100 000 live births. Common anti-Human Platelet Antigen (-HPA) identified in this study were Anti-HPA-5b, Anti-HPA-3a and Anti-HPA-5a. Fifty-eight (58%) (p=0.012) of mothers in the study were younger than 35 years old, of Malay ethnicity and multiparous. Malay mothers were five times more likely to develop FNAIT as compared to non-Malay. For neonates, the most significant factor associated with FNAIT was the neonatal presentation. Symptomatic neonates were more likely to develop FNAIT. Whereas, the neonates onset of presentation, platelet count and blood group were not significantly different than in control group. Conclusion: Incidence of FNAIT among Malaysians was lower than reported in the literature. Malay mothers and neonates presenting with symptoms are more likely to have FNAIT. [ABSTRACT FROM AUTHOR]

Introduction: Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation.Material and Methods: In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations.Results: Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions.Discussion: Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis. [ABSTRACT FROM AUTHOR]

Neonatal alloimmune thrombocytopenia (NAIT) arises from fetomaternal platelet incompatibility that results in transplacental passage of maternal antibodies mostly against fetal human platelet antigens (HPA), whereas NAIT due to anti-human leukocyte antigen (HLA) antibodies is extremely rare. Here, we report a case of Down syndrome (DS) with NAIT that was attributed to HLA antibodies. A boy with DS was delivered at 36 weeks' gestation. His platelet count declined to 13.0 × 109/L, suggestive of NAIT rather than other conditions, including transient abnormal myelopoiesis. Random platelet concentrates and intravenous immunoglobulin administration resolved the thrombocytopenia without clinical complications. Immunoserological investigations detected anti-HLA, but no anti-HPA antibodies in samples from the patient and the mother. HLA typing and cross-matching indicated that anti-HLA antibodies to paternal HLA A31 and B61, which had probably been induced during a prior pregnancy, led to NAIT in this case. Although it is a rare condition, healthcare providers should consider NAIT due to HLA antibodies and be vigilant for subsequent cases in DS. [ABSTRACT FROM AUTHOR]

Platelet-transfusion refractoriness (PTR) is common in patients with hematological malignancies. The etiology of immune PTR is typically human leukocyte antigen (HLA) antibodies (Abs) from pregnancy or previous transfusion. Herein, we report PTR in the setting of induction chemotherapy for acute myelogenous leukemia (AML) from Abs against CD36/glycoprotein (GP)IV. A 66-year-old African American woman presented with anemia and thrombocytopenia. She was found to have transfusion-dependent AML, and a 7 + 3 regimen (7 days of standard-dose cytarabine and 3 days of an anthracycline antibiotic or an anthracenedione, most often daunorubicin) was initiated. The patient developed profound thrombocytopenia, with platelet nadir of 0 by day 13. The results of HLA antibody screening were negative. However, the results of a screening test for platelet-specific antibodies screen showed Abs against cluster of differentiation (CD)36. The platelets of the patient lacked expression of CD36, and DNA analysis showed mutations in the CD36 gene. HLA Ab–mediated PTR is common in patients with hematological malignancies. However, once HLA Abs are excluded, other less-frequent Abs should be considered, particularly in patient populations of Asian, African, or Middle Eastern descent. [ABSTRACT FROM AUTHOR]

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

Background As the frequency of human platelet antigens varies between different ethnic groups and the data about the HPA gene frequency in Iran have been absent yet, the purpose of this study was to determine HPA-1 to HPA-5 and HPA-15 allele frequency among Iranians. Materials and methods HPA-1, HPA-2, HPA-3, HPA-4, HPA-5 and HPA-15 typing was performed by the polymerase chain reaction–sequence-specific primer techniques (PCR-SSP) for 210 subjects [Including 100 blood donors, 55 hematopoietic stem cell (HSC) recipient/donor pairs]. Results The frequencies of HPA phenotypes were determined as follows: HPA- 1a/1a: 98%, HPA-1a/1b:2%, HPA-2a/2a: 8/.5%, HPA-2a/2b: 91·5%, HPA-3a/3a: 21%, HPA-3a/3b: 67·2%, HPA-3b/3b: 22·8%, HPA-4a/4a: 100%, HPA-5a/5a: 99·5%, HPA-5a/5b: 0·5%, HPA-15a/15a: 14·2%, HPA-15a/15b: 67·2% and HPA- 15b/15b: 18·6%. Conclusion HPA-4b was absent and there was not any homozygosity for HPA- 1b/1b, HPA-2b/2b and HPA-5b/5b besides no HPA-1b/b, HPA-2b/b and HPA-5b/ b homozygosity was found. So it seems that HPA-1a, HPA-2a, HPA-4a and HPA-5a might not be involved in the alloimmunization and transfusion reactions on the Iranian population but HPA-15a and HPA3a. Furthermore, extensive studies covering diverse ethnic groups, in the field of platelet immunobiology, will help to find the local pattern more precisely. [ABSTRACT FROM AUTHOR]

Abstract Background Neonatal alloimmune thrombocytopenia (NAIT), caused by maternal antibodies raised against alloantigens carried on foetal platelets, is a very common haematological abnormality in newborns worldwide. However, baseline data on NAIT in China are lacking. Therefore, this study seeks to explore the incidence of alloantibody against the human platelet antigen (HPA) in pregnant women and its associations with NAIT in China. Methods A multicentre, prospective cohort study design will be used, and 55,497 pregnant women will be recruited for the first screening of the anti-HPA antibody at 12 to 28 weeks of gestational age. Subjects who are positive in the first screening for the anti-HPA antibody will be included in the exposure group. Re-tests of the antibody titre, antigen-specificity and genotyping of HPA and HLA will be conducted during admission. A ratio of 1:1 paired individuals with the same ethnicity and parity but testing negative for the anti-HPA antibody will be randomly selected to be included in the non-exposure group. NAIT will be diagnosed in the newborns on day one of the birth. The HPA of the neonates in the exposure group will also be genotyped by sequencing. Associations of maternal HLA with the occurrence of the anti-HPA antibody and correlation of the severity of NAIT with the titre of the anti-HPA antibody will be further analysed. Discussion The study is expected to provide baseline data on NAIT in China. Besides, we hope to find out a population who expresses particular HLA molecules has significant higher risk of HPA alloimmunization in Chinese individuals. We also hope to find a Chinese-specific cut-off antibody titre for the prediction of the severity of NAIT and to provide a means to evaluate the necessity of antenatal treatment. Trial registration ClinicalTrials.gov: NCT02934906 (date registered: 13.10.2016).

Human Platelet Antigen (HPA) is a form of immunogenic polymorphism of platelet membrane glycoproteins. Human Platelet Antigen can cause platelet alloimmunization response will be clinical manifestations of immune thrombocytopenia, such as Fetal Neonatal Allo-immune Thrombocytopenia (FNAIT), Post Transfusion Purpura (PTP), and Platelet Transfusion Refractory (PTR), Idiopathic Thrombocytopenic Purpura (ITP). The aim of this study to research on seroprevalence (genotype and frequency) of Human Platelet Antigen (HPA) in Patients with Non-Immune and immune Thrombocytopenic. A Cross sectional study was conducted to 66 patients with thrombocytopenia, Samples were collected during the period Mei-July 2019, and HPA genotypes were identified in buffy coat blood samples. Samples were examined by PCR examination to detect HPA genotype at Medical-Research Center Laboratory/Medical Faculty of Hasanuddin University Hospital, Makassar. Data was analysis by the statistical tests used were Independent-t, Mann-Whitney, Chi-Square and Fisher Exact tests. The results of the test were significant statistically if the p-value <0.05. Result. From 66 patients thrombocytopena, ages 19-82 years, . 41 (62.1%) women and 25 (37.9%) men. 31 (47.0%) patiens were non immune thrombocytopenia and 35 (53.0%) were Immune Thrombocytopenia. The highest HPA frequency (100%) was HPA-1b, 2a, 4a were obtained in both non-immune and immune thrombocytopenia. In this study, there were frequency of HPA 1b, 15a, in both non-immune and immune thrombocytopenia where was not found in the normal population in Makassar (in our research before). Frequency of HPA-4b (2.8%) was obtained in the population of immune thrombocytopenia that was not found in non-immune thrombocytopenia. The Positive distribution HPA-3b was found to be significantly higher in the Immune group (22.9%) than in the Non-Immune group (3.2%) (p <0.05). Conclusion: The frequency of HPA-3b was found to be significantly higher in immune thrombocytopenia than non-immune thrombocytopenia. [ABSTRACT FROM AUTHOR]

Objective: To described the allele and haplotype frequencies of human leukocyte antigen genes at the -A, -B loci and human platelet antigen genes for human platelet antigen systems 1 to 9, 11 and 15 in blood. Methods: We included 867 healthy unrelated volunteer donors who donated platelets between January 2011 and December 2014. Microarray genotyping was performed using a BeadChip microarray. Medium resolution typing of the human leukocyte antigen at loci A and B was carried out using sequence-specific oligonucleotide probe hybridization. We used multivariate analysis and our human leukocyte antigen population was compared to data from the United States national bone marrow donor program. Human platelet antigen results were compared to a literature review and data from around the world. Results: Our human leukocyte antigen haplotype results were more similar to those of hispanics, followed by caucasians. Likewise, our human platelet antigen sample is more similar to those of Argentina, Rio Grande do Sul and Italy. Conclusion: This was the first article that discusses human platelet antigen and human leukocyte antigen data together. Rare genotypes or antibody associations can make patient management difficult. A blood bank with genotyped donors allows for optimal transfusion and can contribute to better results. Our information can serve as basis for a database of platelet antigen polymorphisms. [ABSTRACT FROM AUTHOR]

AbstractINTRODUCTION:Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.METHODS:Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23) and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13). Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression.RESULTS:There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems.CONCLUSION:The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.

Abstract Fetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal alloimmune neutropenia (NAN) are two rare complications of newborns caused by antibodies against paternal inherited antigens. Human platelet (HPA) and neutrophil antigens (HNA) are the common targets. Human leukocyte antigen (HLA) class I proteins are also expressed on platelets and neutrophils and anti-HLA antibodies have occasionally been implicated in these complications. We report a premature twin infant who presented with severe thrombocytopenia and neutropenia clinically compatible with FNAIT and NAN, from a mother with no identifiable HPA or HNA antibodies, but with very high levels of complement-fixing antibodies against paternal inherited HLA. These antibodies were also detected in the infant. HLA antibodies are commonly present in multiparous women who deliver healthy infants. They can, however, be cytotoxic and cause clinical complications after blood products transfusion (TRALI and becoming refractory to platelets transfusion) and after organ transplantation (allogeneic organ rejection). [ABSTRACT FROM AUTHOR]

Objective: To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT registry.Methods: Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies.Results: Ninety four potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT. NAIT was frequently unanticipated (44 cases, 58%), whilst 32 cases (42%) were anticipated due to personal or family history. In 70/76 cases, the diagnosis of NAIT was made based on HPA antibody results; anti-HPA-1a was most commonly detected (58/70, 82%), followed by anti-HPA-5b (5/70, 7%). Intracranial haemorrhage (ICH) was detected in seven cases (9%). Maternal antenatal therapy resulted in improved clinical outcomes. For antenatally treated cases, whilst 10/29 (34%) neonates had severe TCP, only one ICH was detected.Conclusions: This study provides data on contemporary "real world" management of Australian mothers and babies with NAIT. Antenatal IVIG therapy was associated with better neonatal outcomes. Maternal side-effects and treatment costs were substantial. [ABSTRACT FROM AUTHOR]

Introduction: Fetal and neonatal alloimmune thrombocytopenia is a potentially life-threatening disease with excellent preventative treatment available for subsequent pregnancies. To prevent index cases, the effectiveness of a population-based screening program has been suggested repeatedly. Therefore, we aimed to evaluate women's attitude towards possible future human platelet antigen-screening in pregnancy.Material and Methods: We performed a cross-sectional questionnaire study among healthy pregnant women receiving prenatal care in one of seven participating midwifery practices. Attitude was assessed using a questionnaire based on the validated Multidimensional Measurement of Informed Choice model, containing questions assessing knowledge, attitude and intention to participate.Results: A total of 143 of the 220 women (65%) completed and returned the questionnaire. A positive attitude towards human platelet antigen-screening was expressed by 91% of participants, of which 94% was based on sufficient knowledge. Attitude was more likely to be negatively influenced by the opinion that screening can be frightening. Informed choices were made in 87% and occurred significantly less in women from non-European origin, 89% in European women vs. 60% in non-European women (p = 0.03).Conclusions: Pregnant women in the Netherlands expressed a positive attitude towards human platelet antigen-screening in pregnancy. We therefore expect a high rate of informed uptake when human platelet antigen-screening is implemented. In future counseling on human platelet antigen-screening, ethnicity and possible anxiety associated with a screening test need to be specifically addressed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Human platelet antigens (HPAs) are alloantigens associated with antiplatelet alloantibodies and the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins., Methods: We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls. We analyzed HPA allele frequencies, including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia., Results: In the ITP cohort, HPA2ab, rather than HPA2aa, predicted a low platelet count. HPA2b was associated with the risk of developing ITP. HPA15b was correlated with multiple antiplatelet antibodies. In HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies. HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA compared with those without anti-GPIIb/IIIa antibodies. Overlapping detection was also found among other antiplatelet antibodies and cryoglobulins. Like the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, implying their close relationship. Finally, we extracted cryoglobulins to confirm the exhibition of cryoglobulin-like antiplatelet antibodies. In contrast, in primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M rather than anti-GPIIb/IIIa antibodies., Conclusion: HPA alleles were associated with antiplatelet autoantibodies and had different impacts in primary ITP and HCV-ITP patients. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in HCV patients. The pathophysiology may differ between these two groups., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT., Objectives: To investigate whether a single dose of anti-HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a-negative participants as compared with placebo., Methods: This randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a- and HLA-A2-negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo., Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment-emergent adverse events were possibly related to treatment, both in RLYB211-treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks., Conclusion: These data support the hypothesis that anti-HPA-1a could be used as prophylaxis in women at risk of having an FNAIT-affected pregnancy., Competing Interests: Declaration of competing interests M.Kj., B.S., and J.KK. are stockholders of Prophylix AS, a Norwegian biotech company, which produced the study drug. M.Kj. and J.KK. are currently consultants for Rallybio, which is the sponsor of the study. R.A. and Z.B. are employees of Rallybio. J.KK. also provides consultancy services for ROS Therapeutics, Glycorex Transplantation AB, and Johnson & Johnson. German Red Cross Blood Donor Service Baden-Württemberg-Hessen gGmbH has a contract with Rallybio for the present study. The remaining authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA) with enhanced sensitivity in detecting antibodies against human platelet antigens (HPA), using biotinylated monoclonal antibodies, streptavidin-coated beads and detection by flow cytometry. The beads-MAIPA gave superior signal-to-noise resolution (> 10-fold higher) for detection of anti-HPA-1a and anti-HPA-5b compared with the in-house standard MAIPA. Also, efficient and reproducible detection of anti-HPA-15 (CD109) was shown. The enhanced sensitivity was confirmed using WHO International Reference Reagents for anti-HPA-1a, anti-HPA-3a and anti-HPA-5b, which allowed comparison of detection endpoints with other laboratories. Finally, the beads-MAIPA was validated for quantification of anti-HPA-1a. The lower limit of quantification was 0.4 IU/mL for beads-MAIPA, compared to 1 IU/mL previously reported for standard MAIPA. Based on improved performance against all HPA-antibodies tested, the beads-MAIPA has replaced the standard MAIPA in our laboratory in diagnostics of conditions due to HPA-immunization, such as fetal and neonatal alloimmune thrombocytopenia (FNAIT). [ABSTRACT FROM AUTHOR]

SUMMARY Background Human platelet antigens ( HPAs) are involved in the pathogenesis of several clinical conditions, such as platelet transfusion purpura ( PTP), refractoriness to platelet transfusion and neonatal alloimmune thrombocytopenia ( NAITP). Typing of HPA (1-6 and 15) has not been carried on the Saudi population. This is the first study of all the seven HPA systems on Arabs. The aim of this prospective study was to determine the frequency of HPA (1-6 and 15) in Saudis. Study design and methods A total of 100 randomly selected Saudi blood donor samples were genotyped using the polymerase chain reaction with sequence-specific primers ( PCR-SSP). Results The most common HPA genotypes among Saudis were HPA-1 a + b− (75%), HPA-2 a + b− (62%), HPA-3 a + b− (51·5%), HPA-4 a + b− (99%), HPA-5 a + b− (76·5%), HPA-6 a + b− (100%) and HPA-15 a + b + (50%). The prevalent allele among the HPA systems was (a), except in the HPA-15 system where the (b) allele was found in 52% of the subjects. Comparisons with other ethnic populations uncovered marked differences in the distribution of HPA alleles. Conclusion Studying the prevalence of HPA antigens in Saudi population will help in the understanding of its role in platelet-related disorders. It will also enable the blood bank to establish an HPA-based donor registry that will be a valuable source of compatible platelet-therapeutic products to alloimmunised patients. This will also enhance the safety and efficacy of platelet transfusion. This data obtained will form an addition to the existing body of literature in transfusion research. [ABSTRACT FROM AUTHOR]

Entre outubro de 1997 e julho de 1999 pesquisou-se a refratariedade plaquetária em 15 pacientes na fase precoce do TMO alogênico e autoplástico, com idade variando de 1 a 66 anos no Hospital São Camilo. Para esta avaliação, foram utilizados os seguintes parâmetros: evolução clínica, cálculo corrigido do incremento plaquetário (CCI), teste de microlinfocitotoxicidade dependente de complemento (CDC) e ensaios plaquetários por aderência de células vermelhas em fase sólida (SPRCA). A refratariedade plaquetária foi definida como falha de resposta a uma transfusão de dois concentrados de plaquetas ABO compatíveis, quando o cálculo corrigido do incremento plaquetário (CCI) de uma hora pós-transfusional era inferior a 7,5 ou de 24 horas < 4,5. Apenas a análise do CCI de 24 horas mostrou significância estatística. A refratariedade plaquetária foi detectada em 80,0 % dos casos, tendo como causa principal os fatores não imunológicos, como: anfotericina 66,66%, doença veno-oclusiva hepática 53,33%, febre de origem indeterminada 40,0%, esplenomegalia epistaxe leve, febre, melena grave, hematêmese grave e infecção bacteriana 20,0%. Melena leve, enterorragia grave, epistaxe moderada e grave 13,33%, enquanto CIVD, enterorragia moderada e grave 6,66%. Os fatores imunológicos foram representados pela presença da reação aguda do enxerto contra hospedeiro (aGVHD) em 33,0% e infecção por citomegalovírus (CMV) em 13,33%, embora a detecção de auto-anticorpos tenha sido negativa. Conclui-se que a análise do CCI pós-transfusional de 24 horas mostrou ser um método de escolha para detecção da refratariedade e de útil aplicabilidade em pacientes trombocitopênicos refratários, em particular naqueles submetidos ao TMO.From October 1997 to July 1999, platelet refractoriness was studied in 15 patients, aged from 1 to 66 years old, in the early stage of allogeneic and autologous BMT, carried out at the São Camilo Hospital. The following parameters were used for this analysis: daily clinical progress, 1- and 24 hour-post-transfusion platelet corrected count increment (CCI),complement-dependent microlymphocytotoxicity test (CDC) sensitized by human antiglobulin (AGH) and solid phase red blood cell adherence (SPRCA) platelet analysis. Platelet concentrated products were obtained from automated cell separator machines, filtered through retention filters of pre-storage leukocyte reduction and, subsequently, stored at room temperature for a maximum of 96 hours. Each platelet unit featured on average 0.51 x 10(4) leukocytes, with platelet cell counts of 3.58 x 10(11). The mean pH of each thrombocytapherese concentrate was 6.34 and was storage for 32 hours and 21 minutes. Platelets concentrates were transfused on a prophylactic basis, when the platelet counts were below 20 x 10(9) /L or above these values in cases of therapeutic intervention or bleeding. The platelet refractory potential was defined as the lack of response to a transfusion of two compatible ABO platelet concentrate products confirmed by the reduction in platelet CCI 1 hour after transfusion was less than 7.5 or 24 hours after transfusion was less than 4.5. Only the 24-hour CCI analysis showed statistically significance with the platelets refractoriness occurring in 80.0% of the cases, as a consequence of non-immune factors, such as, amphotericin 66.66%, veno-occlusive disease 53.33 %, undetermined fever 40.0%, splenomegaly, slight nose bleeds, fever, severe melene, severe hematemesis and bacterial infection, 20.0%. Slight melene, severe enterorrhagia and moderate and severe nose bleeds 13.33%, whereas CIVD, moderate and severe enterorrhagia were 6.66%. The presence of immune factors was detected by GVHD and CMV infections that were identified in 33.33% and 13.33% of the cases, respectively, although the detection of autoantibodies was negative. The conclusion is that the 24-hour post-transfusion CCI analysis has proven to be a predictor of platelet refractoriness and a useful test in refractory thrombocytopenic patients, mainly those undergoing BMT.

Background: Due to the presence of platelet antigen polymorphisms, human platelet membrane glycoproteins can be identified as an alloantigen or autoantigen. The aim of this study was to determine the frequencies of human platelet antigens (HPAs)-1 to-5 and-15 in Turkmen blood donors and establish a panel of accredited HPAs negative donors as well as an HPA-typed platelet donor registry., Materials and Methods: HPA-1 to-5 and-15 typing was performed by the polymerase chain reaction-sequence-specific primer techniques on 80 unrelated Turkmen donors who were referred to Aq-Qala Blood Transfusion Center in Golestan Province from September 2018 to October 2019., Results: The frequencies of HPA phenotypes were determined as follows: HPA-1aa: 92.5%, HPA-1ab: 7.5%, HPA-2aa: 77.5%, HPA-2ab: 20.0%, HPA-2bb: 2.5%, HPA-3aa: 75.3%, HPA-3ab: 50%, HPA-3bb: 11.2%, HPA-4aa: 100%, HPA-5aa: 78.5%, HPA-5ab: 21.5%, HPA-15aa: 41.2%, HPA-15ab: 56.2% and HPA-15bb: 17.5%., Conclusion: Determining the genotype of HPAs that play an important role in platelet refractory can improve the management of alloimmunization due to the incompatibility of HPAs between the recipients and donors. Therefore, the registration process for national platelet donors can help patients accelerate and improve the quality of transfused platelets., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

The detection of the most significant erythrocyte antigens present in each one of the individuals is fundamental when carrying out a transfusion or a transplant. Detection to date is performed by conventional serological methods through the antigen-antibody reaction. But several drawbacks may arise depending on the pathology under study, limiting the availability of blood components. Molecular methods such as genotyping is a tool that complements sensitivity and specificity and has come to revolutionize immunohematology in the blood bank, allowing not only the detection of erythrocyte antigens but also platelet antigens. These methodologies are applicable in patients and in large-scale donors, starting from the allelic variants present in each of the genes that code for the antigens of clinical interest, using microarray systems or systems based on particles labeled with specific probes or their variants that allow an analysis from the immunohematological point of view., (© 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Objectives The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)-1 to -6 and -15 systems in five Malay sub-ethnic groups in Peninsular Malaysia. Background: HPAs are polymorphic glycoproteins expressed on the surface of platelet membranes and are genetically differentiated across ethnogeographically unrelated populations. Methods: Blood samples were obtained with informed consent from 192 volunteers: Banjar (n=30), Bugis (n=37), Champa (n=51), Jawa (n=39) and Kelantan (n=35). Genotyping was done using polymerase chain reaction-sequence specific primer method. Results: In general, frequencies of HPAs in the Malay sub-ethnic groups are more similar to those in Asian populations compared with other more distinct populations such as Indians, Australian Aborigines and Europeans. Conclusions: This study provides the firstHPA datasets for the selected Malay sub-ethnic groups. Subsequent analyses including previously reported HPA data of Malays, Chinese and Indians revealed details of the genetic relationships and ancestry of various sub-populations in Peninsular Malaysia. Furthermore, the comprehensive HPA allele frequency information from Peninsular Malaysia provided in this report has potential applications for future study of diseases, estimating risks associated with HPA alloimmunization and for developing an efficient HPA-typed donor recruitment strategy. [ABSTRACT FROM AUTHOR]

Studies have reported the polymorphism of human platelet antigen (HPA)-17w, -18w, -19w, -20w, and -21w. However, the distribution of these five antigens in Chinese Cantonese is still unknown. In this study, we designed new sequence-specific primers for HPA-19w to -21w and used published primers for HPA-17w and -18w to develop a polymerase chain reaction with the sequence-specific primers (PCR-SSP) method for simultaneously genotyping HPA-17w to -21w. A total of 820 unrelated Cantonese apheresis platelet donors in Guangzhou were involved in this study. Among the five HPAs, complete a/a homozygosity was observed for HPA-17w to -20w with an allele frequency of 1.0000. For HPA-21w, nine individuals (9/820, 1.10%) were found to be HPA-21a/bw heterozygous and the allele frequencies of HPA-21a and HPA-21bw were 0.9945 (1631/1640) and 0.0055 (9/1640), respectively. The reliability of the PCR-SSP method was determined by comparing with the genotyping results by DNA sequencing, and no inconsistencies were observed between the two methods. This study provides a reliable PCR-SSP method for simultaneously genotyping HPA-17w to -21w and could improve HPA-matched platelet transfusion in Chinese Cantonese. [ABSTRACT FROM AUTHOR]