Introduction: Graves’ disease is associated with various hematological abnormalities, including anemia, leucopenia, and thrombocytopenia. However, pancytopenia involving all three cell lines is a rare and often under-recognized manifestation of thyrotoxicosis. We present a case of newly diagnosed Graves’ disease complicated by pancytopenia, in which cell counts normalized rapidly following carbimazole initiation. Case: A 51-year-old female with underlying type 2 diabetes mellitus, hypertension, and dyslipidemia presented with dysphagia for 3 months, significant weight loss (from 95 to 75 kg over 6 months), and a 1-week history of fever, palpitations, tremors, orthopnea, and bilateral lower limb swelling. On examination, she was febrile (38.2°C) with bibasal crepitations, pitting edema up to the midshins, bilateral hand tremors, and a multinodular neck mass moving with deglutition. Investigations confirmed thyrotoxicosis (thyroid-stimulating hormone [TSH] 0.01 mIU/L, free T4 130.1 pmol/L, T3 >30.8 pmol/L) with positive autoantibodies (thyroid receptor antibody 31.9 IU/L, anti-thyroid peroxidase 195 IU/mL). Full blood count showed pancytopenia: white cell count 2.73 × 10⁹/L, hemoglobin 10.3 g/dL, and platelets 108 × 10⁹/L. Peripheral blood film suggested normocytic normochromic anemia with leucopenia and thrombocytopenia. Chest radiography showed cardiomegaly with fluid overload, and echocardiography revealed an ejection fraction of 77%. She was treated for impending thyroid storm secondary to pneumonia with Lugol’s iodine, hydrocortisone, propylthiouracil, and intravenous antibiotics. She was discharged on day 3 with a transition to carbimazole. At outpatient follow-up approximately 9 days later, thyroid function had improved significantly (free thyroxine 4 reduced from 130.1 to 29.34 pmol/L with suppressed TSH), and repeat full blood count demonstrated complete normalization of all three cell lines. Conclusion This case illustrates that pancytopenia can be a direct consequence of severe thyrotoxicosis and may reverse completely with effective antithyroid therapy. The temporal relationship between biochemical improvement and hematological recovery supports a causal link. Clinicians should be aware of this rare association to avoid misdiagnosis and unnecessary invasive investigations.
Pancytopenia ; Graves Disease ; Thyrotoxicosis

Introduction: Autoimmune thyroid disease is frequently associated with other immune-mediated disorders; however, clinically significant pancytopenia is rare. In patients with Graves’ disease receiving antithyroid therapy, leukopenia raises concern for drug-induced agranulocytosis, a rare but potentially life-threatening complication characterized by severe neutropenia requiring immediate drug withdrawal. The coexistence of hemolytic anemia and thrombocytopenia may instead suggest Evans syndrome, defined by autoimmune hemolytic anemia with immune thrombocytopenia, with or without neutropenia. Importantly, uncontrolled thyrotoxicosis itself may cause immunemediated cytopenias, creating a diagnostic challenge. Case: We report a 55-year-old female with thyroid receptor antibody-positive Graves’ disease who presented with jaundice and pancytopenia while receiving carbimazole therapy. Laboratory evaluation demonstrated anemia with reticulocytosis and a positive direct antiglobulin test, thrombocytopenia and leukopenia. Complement testing revealed reduced C3 with normal C4, consistent with immune-mediated hemolysis. Peripheral blood film showed no blast cells or marrow infiltration, and autoimmune screening, including antinuclear antibodies and anti–double stranded DNA, was negative. The coexistence of Coombs-positive hemolysis and thrombocytopenia initially raised suspicion for Evans syndrome, while leukopenia during carbimazole therapy prompted concern for drug-induced agranulocytosis. However, neutropenia was not severe, and the absence of marrow infiltration or systemic autoimmune disease made alternative causes of pancytopenia less likely. Importantly, blood counts progressively improved following the optimization of thyroid control despite continuation of carbimazole at a reduced dose, without the use of immunosuppressive therapy. This clinical course supported the interpretation of thyrotoxicosis-associated immune cytopenia rather than primary Evans syndrome or carbimazole-induced agranulocytosis. Conclusion This case highlights thyrotoxicosis-associated immune cytopenia as an important mimic of Evans syndrome and carbimazole-related hematological toxicity. Recognizing this entity is essential to avoid unnecessary discontinuation of antithyroid therapy or inappropriate immunosuppressive treatment.
Evans Syndrome ; Carbimazole ; Pancytopenia ; Agranulocytosis ; Graves Disease

OBJECTIVE: To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs). METHODS: A total of 28 unrelated CFDs patients admitted to Wenzhou People's Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg:C), fibrinogen antigen (Fg:Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted byPolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People's Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment. RESULTS: The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. CLINICAL DATA: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg:C. Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c.902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c.569 A>G (28.6%, 8/28). Biological informatics analysis: the Aα c.180+1G>T mutation was predicted to be highly deleterious. And the Aα c.104G>A, Bβ c.425T>G, Bβ c.586C>T, and γ c.902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c.104G>A, Aα c.180+1G>T, Bβ c.425T>G, Bβ c.569A>G, Bβ c.586C>T, Bβ c.643G>A, γ c.901C>T, γ c.902G>A, γ c.1001A>C) were classified as pathogenic, while one variation (γ c.908C>G) was classified as likely pathogenic. CONCLUSION In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.
Humans ; Female ; Male ; Afibrinogenemia/congenital* ; Fibrinogen/metabolism* ; Mutation ; Genotype ; Adult ; Child ; Adolescent ; Child, Preschool ; Infant

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

OBJECTIVE: To explore the clinical and genetic characteristics of fetuses with Kabuki syndrome (KS) and their genotype-phenotype correlation. METHODS: A retrospective analysis was carried out on the prenatal manifestations and results of genetic testing of six KS fetuses diagnosed by whole-exome sequencing (WES). The findings were compared with 28 prenatally diagnosed KS cases reported in the literature to summarize the prenatal features of KS. This study has been approved by the Ethics Committee of Maternal and Child Health Care Hospital of Hubei Province (Ethics No.: 2025-141-01). RESULTS: Prenatal ultrasound findings in KS fetuses showed high heterogeneity. The most common abnormalities were cardiac (23/35, 65.7%) and renal (20/35, 57.1%), which are often accompanied by amniotic fluid abnormalities (5/35, 14.3%), single umbilical artery (5/35, 14.3%), and fetal hydrops (4/35, 11.4%). Among the six fetuses from our center, all were identified by WES to harbor pathogenic variants of the KMT2D gene, and all of which were de novo. These included 3 frameshift variants, 2 nonsense variant, and 1 missense variant, among which 4 were unreported previously. CONCLUSION This study has expanded the mutational spectrum of the KMT2D gene. Prenatal ultrasound findings of KS lack specificity, though multi-system anomalies or specific soft markers may indicate KS. WES is an effective tool for the diagnosis, and KS should be included in the differential diagnosis list for prenatal cardiac and renal abnormalities.
Humans ; Hematologic Diseases/diagnostic imaging* ; Face/diagnostic imaging* ; Female ; Vestibular Diseases/diagnostic imaging* ; Abnormalities, Multiple/diagnostic imaging* ; Pregnancy ; Ultrasonography, Prenatal ; Adult ; Neoplasm Proteins/genetics* ; Retrospective Studies ; DNA-Binding Proteins/genetics* ; Male ; Exome Sequencing ; Fetus/diagnostic imaging* ; Genetic Association Studies ; Mutation

OBJECTIVE: To investigate the molecular mechanism for a family with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The proband, a 63-year-old female, was admitted to the First Affiliated Hospital of Wenzhou Medical University in August 2024 for lumbar disc herniation. Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), and FⅫ activity (FⅫ:C), were carried out for the proband and her family members (9 individuals from three generations) using a one-stage clotting assay. The level of FⅫ antigen (FⅫ:Ag) was determined with an Enzyme-linked immunosorbent assay (ELISA). Sanger sequencing was conducted to identify potential variants in the F12 gene. Multiple in silico tools were used to predict the conservation, hydrophobicity, and structural impact of the identified variants. Recombinant expression plasmids were constructed and transiently transfected into HEK293T cells. The recombinant FⅫ protein was analyzed using Western blotting (WB) and ELISA. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband showed a markedly prolonged APTT (160.3 s) and significantly decreased FⅫ:C (2%) and FⅫ:Ag (5%) levels. Analysis of the F12 gene sequence revealed a 46C/T genotype in the promoter region, a heterozygous c.1457G>A (p.Cys467Tyr) missense variant in exon 12, and a heterozygous c.1561G>A (p.Glu502Lys) missense variant in exon 13. Bioinformatic analysis showed that the p.Cys467 is highly conserved across various species, and the p.Cys467Tyr variant may affect local structural stability of the FⅫ protein. The p.Cys467Tyr variant had no effect on the transcription of the F12 gene. However, the variant has significantly decreased the FⅫ:Ag levels and FⅫ protein expression in the cell culture supernatant compared to the wild-type expression vector, while in the cell lysate, it is higher than the wild-type expression vector. In other words, the p.Cys467Tyr variant has probably caused a secretion defect of FⅫ protein. CONCLUSION The 46C/T genotype, the heterozygous p.Cys467Tyr missense variant, and the heterozygous p.Glu502Lys missense variant are associated with reduced plasma FⅫ levels in this pedigree. The p.Cys467Tyr variant, which was unreported previously, did not affect the synthesis of FⅫ but may have resulted in a secretion defect.
Humans ; Female ; Middle Aged ; Mutation, Missense ; Pedigree ; HEK293 Cells ; Male ; Factor XII/genetics* ; Adult ; Factor XII Deficiency/genetics*

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic

OBJECTIVES: To investigate the readmission rate and risk factors for readmission due to hyperbilirubinemia in neonates with ABO hemolytic disease of the newborn (ABO-HDN), and to construct a risk prediction model for readmission. METHODS: Neonates diagnosed with hyperbilirubinemia due to ABO-HDN and hospitalized in the neonatal department between January 2021 and December 2023 were enrolled. Based on readmission status, neonates were divided into a readmission group and a control group. Clinical characteristics related to hyperbilirubinemia and risk factors for readmission were analyzed. Subsequently, a prediction model for readmission was constructed, and its predictive performance was evaluated. RESULTS: A total of 483 neonates with hyperbilirubinemia due to ABO-HDN were included. The readmission rate was 13.0% (63 cases). Multivariate logistic regression analysis revealed that earlier age at phototherapy initiation, longer duration of phototherapy, occurrence of rebound hyperbilirubinemia, and higher levels of serum total bilirubin and indirect bilirubin at discharge were independent risk factors for hyperbilirubinemia readmission in ABO-HDN neonates (OR=2.373, 4.840, 6.475, 5.033, 1.336 respectively; P<0.05). A risk prediction model for ABO-HDN hyperbilirubinemia readmission was constructed based on these 5 risk factors. Model evaluation demonstrated good predictive performance. CONCLUSIONS Age at phototherapy initiation, duration of phototherapy, occurrence of rebound hyperbilirubinemia, and serum total bilirubin and indirect bilirubin levels at discharge are significant influencing factors for readmission due to hyperbilirubinemia in neonates with ABO-HDN. Close monitoring during discharge planning and follow-up management for such neonates is crucial to reduce readmission rates.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Risk Factors ; Patient Readmission ; Male ; Female ; Logistic Models ; Hyperbilirubinemia, Neonatal/therapy* ; Erythroblastosis, Fetal ; Bilirubin/blood*