OBJECTIVE: To investigate the pathogenesis and clinical diagnosis of fetal/neonatal alloimmune thrombocytopenia (FNAIT) and analyze the laboratory test results and clinical data related to the disease, so as to provide reference for clinical treatment and improvement of prognosis. METHODS: The clinical data of six neonatal patients with FNAIT in the Neonatology Department of our hospital from March 2017 to September 2020 were retrospectively analyzed, which included laboratory diagnosis, clinical symptoms, treatment, and prognosis. RESULTS: Among six patients, two cases occurred in the first pregnancy and four cases in the second pregnancy. The platelet count of six cases were decreased at admission or during hospitalization and maternal and neonatal serum autoimmune platelet antibody tests were positive. Five cases were accompanied by different degrees of skin and facial bleeding spots or petechiae and ecchymosis, intracranial hemorrhage. Four cases were treated with immunoglobulin and/or steroid hormone therapy (one of them received cross-matched platelets transfusion), while the symptoms of the other two cases improved spontaneously. Five cases recovered and were discharged from the hospital, while one case had not recovered but the family members requested to be discharged forwardly. Four cases were hospitalized within two weeks, but two cases were hospitalized for more than two weeks due to other diseases or factors (e.g., neonatal sepsis, neonatal enteritis, congenital heart disease, neonatal asphyxia, etc.). CONCLUSION FNAIT is characterized by decreased platelet count, with or without bleeding symptoms, and may occur in the first and following pregnancy. FNAIT can recover spontaneously or have a good prognosis after treatment. However, the complication with other diseases or factors may affect the prognosis.
Adult ; Aged ; Antigens, Human Platelet ; Data Analysis ; Female ; Hemorrhage ; Humans ; Infant, Newborn ; Middle Aged ; Platelet Count ; Platelet Transfusion/adverse effects* ; Pregnancy ; Retrospective Studies ; Thrombocytopenia, Neonatal Alloimmune/therapy*

Neonatal thrombocytopenia, defined as platelet counts of less than 150,000/µL, is a frequent hematologic abnormality in neonatal period. Differential diagnosis of neonatal thrombocytopenia may be challenging to pediatric hematologists and neonatologists because neonatal thrombocytopenia is associated with diverse maternal or neonatal clinical conditions. An accurate diagnosis for neonatal thrombocytopenia will lead to appropriate evaluation and management. Platelet transfusion is the primary management of neonatal thrombocytopenia. Most thrombocytopenic newborns received platelet concentrates to prevent major hemorrhage or treat ongoing bleeding according to institutional policy. However, scientific evidences for benefit and consistent guideline for platelet transfusion in neonates are lacking, further investigation to establish the standard recommendation for platelet transfusion is needed. This article reviewed the diagnostic approach and current guideline for platelet transfusion management for neonatal thrombocytopenia.
Blood Platelets ; Diagnosis ; Diagnosis, Differential ; Hemorrhage ; Humans ; Infant ; Infant, Newborn ; Organizational Policy ; Platelet Count ; Platelet Transfusion ; Thrombocytopenia ; Thrombocytopenia, Neonatal Alloimmune

PURPOSE: This study investigated predictive factors for severe neonatal thrombocytopenia, which greatly increases the need for intensive care and is associated with a high mortality rate in premature infants. Factors adopted for prompt identification of at-risk newborns include blood test results and birth history. This study analyzed the relationship between the presence of severe neonatal thrombocytopenia and the mortality rate. The causes of thrombocytopenia in premature infants were also examined. METHODS: This retrospective study evaluated 625 premature infants admitted to the neonatal intensive care unit (NICU) at Chung-Ang University Medical Center. The neonates were classified into 3 groups according to the severity of thrombocytopenia: mild (100×10⁹/L≤platelet < 150×10⁹/L), moderate (50×10⁹/L≤platelet < 100×10⁹/L), or severe (platelet < 50×10⁹/L). Analysis of blood samples obtained at the onset of thrombocytopenia included platelet count, white blood cell (WBC) count, hemoglobin level, hematocrit level, absolute neutrophil count, and high-sensitivity C-reactive protein level. RESULTS: Of the 625 premature infants admitted to our NICU, 214 were detected with thrombocytopenia. The mortality rate in thrombocytopenic neonates was 18.2% (39/214), whereas a mortality rate of only 1.0% was observed in non-thrombocytopenic neonates. The major causes of thrombocytopenia were perinatal insufficiency and sepsis in premature infants. Severe thrombocytopenia was noted more frequently in premature infants with higher WBC counts and in those with a younger gestational age. CONCLUSION: Platelet count, WBC count, and gestational age are reliable predictors for severe neonatal thrombocytopenia. The major causes of thrombocytopenia were perinatal insufficiency and sepsis in premature infants.
Academic Medical Centers ; C-Reactive Protein ; Classification ; Critical Care ; Gestational Age ; Hematocrit ; Hematologic Tests ; Humans ; Infant, Newborn ; Infant, Premature ; Intensive Care, Neonatal ; Leukocytes ; Mortality ; Neutrophils ; Platelet Count ; Reproductive History ; Retrospective Studies ; Sepsis ; Thrombocytopenia ; Thrombocytopenia, Neonatal Alloimmune

BACKGROUND: Platelet antigen and antibody tests have been used in platelet immunological disorders, such as neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP). Mixed passive hemagglutination (MPHA) method has several advantages, including frozen preservation of platelets, ability to differentiate between anti-HLA and platelet-specific antibodies, and quick and easy interpretation without expensive equipment. In this study, we intended to develop the MPHA method using indicator cells of anti-Rh(D) sensitized group O, Rh+ RBCs. METHODS: We made indicator cells sensitized with anti-Rh(D) with various strengths (1:32 to 1:256) and determined the optimal strength. We determined the sensitivity of the MPHA and compared the results using flow cytometry. We observed the changes of the reaction according to the storage time of indicator cells. RESULTS: The optimal sensitization strengths of the indicator cells were 1:192 and 1:256. MPHA showed strong positive results with 1:8,192 diluted positive control, while the detection limit of flow cytometry was 1:128. Until the second week (mean 16 days), the indicator cells showed good results comparable to those of fresh ones. CONCLUSION: We developed the MPHA method using indicator cells of anti-Rh(D) sensitized group O, Rh+ RBCs. We produced the indicator cells in our own laboratory and obtained platelet panels with rare antigen typing using frozen-stored platelets. This technology will be used effectively for detection of platelet antigens and identification of platelet antibodies and also for platelet crossmatching.
Antibodies ; Blood Platelets* ; Flow Cytometry ; Hemagglutination* ; Limit of Detection ; Purpura ; Thrombocytopenia, Neonatal Alloimmune

BACKGROUND: We aimed to investigate which factors in the clinical profile of mothers with idiopathic thrombocytopenic purpura (ITP) can predict neonatal risk of thrombocytopenia. METHODS: Data was retrospectively collected from all pregnant women with ITP who presented to our institution between 2001 and 2013. Neonatal offspring of these women were classified into 2 groups based on the presence or absence of neonatal thrombocytopenia (platelet count <100x109/L). Several parameters were compared between the 2 groups, including maternal age, maternal platelet count, maternal treatment history, and thrombocytopenia in siblings. We further examined the correlation between maternal platelet count at the time of delivery and neonatal platelet count at birth; we also examined the correlation between the minimum platelet counts of other children born to multiparous women. RESULTS: Sixty-six neonates from 49 mothers were enrolled in the study. Thrombocytopenia was observed in 13 (19.7%) neonates. Maternal treatment for ITP such as splenectomy did not correlate with a risk of neonatal thrombocytopenia. Sibling thrombocytopenia was more frequently observed in neonates with thrombocytopenia than in those without (7/13 vs. 4/53, P<0.01). No association was observed between maternal and neonatal platelet counts. However, the nadir neonatal platelet counts of first- and second-born siblings were highly correlated (r=0.87). CONCLUSION: Thrombocytopenia in neonates of women with ITP cannot be predicted by maternal treatment history or platelet count. However, the presence of an older sibling with neonatal thrombocytopenia is a reliable risk factor for neonatal thrombocytopenia in subsequent pregnancies.
Child ; Female ; Humans ; Infant, Newborn ; Maternal Age ; Mothers ; Parturition ; Platelet Count ; Pregnancy ; Pregnant Women ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Risk Factors ; Siblings ; Splenectomy ; Thrombocytopenia ; Thrombocytopenia, Neonatal Alloimmune*

This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b.
Antigens, Human Platelet ; genetics ; China ; Female ; Genotype ; Humans ; Infant, Newborn ; Purpura, Thrombocytopenic, Idiopathic ; diagnosis ; genetics ; Thrombocytopenia, Neonatal Alloimmune ; diagnosis ; genetics

BACKGROUND: Alloimmunization of human platelet antigens (HPA) is associated with clinically significant disease, such as platelet refractoriness, neonatal alloimmune thrombocytopenia, or posttransfusion purpura. It is determined by single nucleotide polymorphism of genes for platelet membrane glycoprotein. To date, approximately 27 HPAs have been discovered, and their frequencies differ depending on ethnicity and country. METHODS: We conducted an investigation of prevalence of HPA in the Korean population using a multiplex single-base primer extension reaction (SNaPshot). With 84 specimens from healthy donors, HPA genotyping was performed on 11 different HPAs, including HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -13, and -15. RESULTS: A total of 90 blood samples were genotyped. The genotype frequencies of HPA were as follows: HPA-1a/1a: 100.0%, -2a/2a: 83.3%, -2a/2b: 14.3%, -2b/2b: 2.4%, -3a/3a: 39.3%, -3a/3b: 52.4%, -3b/3b: 8.3%, -4a/4a: 100.0%, -5a/5a: 95.2%, -5a/5b: 4.8%, -6a/6a: 94.0%, -6a/6b: 6.0%, -7a/7a: 100.0%, -8a/8a: 100.0%, -9a/9a: 97.6%, -9a/9b: 2.4%, -13a/13a: 100.0%, -15a/15a: 23.8%, -15a/15b: 51.2%, and -15b/15b: 25.0%. CONCLUSION: The SNaPshot assay was employed for detection of SNPs in various clinically significant HPA genes. In addition to well-known frequencies of previously reported HPA-1 to -8, this study showed frequencies of HPA-9, -13, and -15 in Koreans for the first time. The SNaPshot technique might be suitable for use in actual clinical testing in patients with platelet alloimmunization.
Antigens, Human Platelet ; Blood Platelets ; Genotype ; Humans ; Membrane Glycoproteins ; Polymorphism, Single Nucleotide ; Prevalence ; Purpura ; Purpura, Thrombocytopenic ; Thrombocytopenia, Neonatal Alloimmune ; Tissue Donors

OBJECTIVETo explore the diagnosis and treatment of a case of neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti HPA-3a antibody.

METHODSThe platelet counts and purpuric symptom in the newborn were clinical examined. The HPA-1-21bw genotypes of the newborn and his parents were detected by multiple DNA-PCR, gene sequencing and genotyping. The HPA specificity antibody in the sera of newborn and his mother were detected by flow cytometry (FCM), and the HPA specificity antibody was identified by monoclonal antibody-specific immobilization of platelet antigens (MAIPA).

RESULTSThe newborn had the typical symptom of NAITP, multiple subcutaneous petechia, hematuria and coffee-like vomitus. The HPA genotype of the newborn was HPA-3ab, while that of his mother and his father were HPA-3bb and HPA-3aa, respectively. The sera of newborn and his mother existed antibody against the platelet of newborn's father. The HPA antibody of the newborn and his mother were identified as anti HPA-3a. The newborn was approved a patient of NAITP caused by anti HPA-3a antibody.

CONCLUSIONThe diagnosis and treatment for NAITP newborn caused by anti HPA-3a antibody in this study was the first domestic report. It could provide successful experiences and references for the similar cases.

Antibody Specificity ; immunology ; Antigens, Human Platelet ; immunology ; Genotype ; Humans ; Infant, Newborn ; Isoantibodies ; adverse effects ; immunology ; Male ; Thrombocytopenia, Neonatal Alloimmune ; etiology ; immunology

Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies react to antigens expressed on fetal platelets, which is mainly platelet-specific alloantigen or HLA, resulting in their immune destruction. Here, we described a patient who suffered from NAIT caused by anti-HLA-A2 antibody. Sera from the mother and the newborn were screened for human platelet antigen-specific antibodies and HLA antibodies by ELISA, and HLA antibodies were detected in both of them. The antibody specificity was identified as anti-HLA-A2 by Luminex single antigen bead assay. HLA typing results showed that patient's father descended HLA-A2 antigen on the patient and the mother was HLA-A2 negative. It is most conceivable that anti-HLA-A2 alloantibody in the mother's sera crossed the placenta and subsequently caused NAIT in the case presented. The patient received platelet concentrates, oral steroid and intravenous globulin and platelet count increased to 120x10(9)/L on the 90th day of life. The Luminex single antigen bead assay used in this case is highly sensitive and specific assay to determine antibody specificity and it is faster and more convenient for routine use in clinical laboratory so that this assay could be useful to diagnose NAIT caused by HLA antibodies and treat such NAIT patients with HLA matched platelet transfusion.
Antibodies ; Antibody Specificity ; Blood Platelets ; Enzyme-Linked Immunosorbent Assay ; Fathers ; Histocompatibility Testing ; HLA-A2 Antigen ; Humans ; Infant, Newborn ; Isoantibodies ; Isoantigens ; Mothers ; Placenta ; Platelet Count ; Platelet Transfusion ; Thrombocytopenia, Neonatal Alloimmune

Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease. Conventional view considered its pathogenesis as the destruction of platelets induced by platelet associated antibodies, the target of treatment are inhibiting the production of antibodies and blocking the destruction of platelets in reticuloendothelial system, but they are ineffective in part of ITP patients, who transform to chronic/refractory ITP (C/RITP). As to children's C/RITP, the effect of first-line therapy is low, while the second-line therapy isn't effective definitely and has obvious side effects. The safe and effective second-line drugs to prevent disease progressing are urgently required. Recently, a pathogenesis that decrease the platelet production has been confirmed, thrombopoietic drugs, including thrombopoietin (TPO) and its receptor agonist (TRA), are under research and clinical application gradually. Recombinate human TPO (rhTPO) has accomplished Phase III clinical trails in adult C/RITP and tumor children. The Phase III clinical trails of romiplostim and eltrombopag, as the representative of TRA, in adult C/RITP have been performed. There are also two clinical trails of TRA for children's C/RITP, the efficacy and safety have been approved, with the convenience for using. In pediatric population, they have a good clinical application. In this article the research and development of thrombopoietic drugs and their perspective in pediatric clinical use are reviewed.
Child ; Clinical Trials, Phase III as Topic ; Humans ; Thrombocytopenia ; drug therapy ; etiology ; Thrombocytopenia, Neonatal Alloimmune ; drug therapy ; Thrombopoietin ; therapeutic use