1.Immune-Mediated Pancytopenia Associated with Graves’ Disease Mimicking Evans Syndrome and Carbimazole-Induced Agranulocytosis
Ahmad Syahmi Yusof Zaki ; Ezelea Elwina Walter Sandosam ; Nur Izat Muhamad ; Wan Mohd Izani Wan Mohamed
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):103-
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
2.Graves' Disease Presenting with Pancytopenia: A Rare Reversible Hematological Abnormality in Thyrotoxicosis
Wei Ton Wong ; Che Azzah Hanim Che Yahya ; Nurul Atikah Abdul Aziz
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):108-
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
3.The Chinese guidelines for the diagnosis and treatment of invasive fungal disease in patients with hematological disorders and cancers (the seventh revision).
Chinese Journal of Internal Medicine 2025;64(12):1155-1168
In 2005, the Chinese Invasive Fungal Infection Working Group published the first guidelines for the diagnosis and treatment of invasive fungal disease (IFD) in patients with hematological disorders and cancers, with the sixth revision released in 2020. Numerous advances in the fields of hematological oncology treatment and the diagnosis and management of IFD have significantly influenced the corresponding strategies. Therefore, the Chinese Invasive Fungal Infection Working Group has reviewed key research advances from 2020 to 2024 and released the seventh revision of the Chinese guidelines. Major revisions include: changes in the epidemiology of IFD; evaluation of novel diagnostic methods (especially PCR and metagenomic next-generation sequencing); updated recommendations on therapeutic drug monitoring and in vitro drug sensitivity test; management of breakthrough IFD; targeted therapy of Pneumocystis jiroveci pneumonia and cryptococcosis; and updated recommendation on the duration of antifungal therapy.
Humans
;
Invasive Fungal Infections/drug therapy*
;
Hematologic Diseases/complications*
;
Antifungal Agents/therapeutic use*
;
Neoplasms/complications*
;
Hematologic Neoplasms/complications*
;
Mycoses/therapy*
;
China
4.High mobility group protein B1(HMGB1) promotes myeloid dendritic cell maturation and increases Th17 cell/Treg cell ratio in patients with immune primary thrombocytopenia.
Qinzhi LI ; Dongsheng DUAN ; Xiujuan WANG ; Mingling SUN ; Ying LIU ; Xinyou WANG ; Lei WANG ; Wenxia FAN ; Mengting SONG ; Xinhong GUO
Chinese Journal of Cellular and Molecular Immunology 2025;41(1):45-50
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
5.Research on the anti-inflammatory effects of a novel sleep-aid decoction on elderly insomnia patients across traditional Chinese medicine constitutional types.
Zhen WU ; Zhuoqiong BIAN ; Ailin CHEN ; Qiuping ZHANG ; Jie LI ; Hui ZHOU ; Hongying ZHU
Chinese Journal of Cellular and Molecular Immunology 2025;41(11):1007-1012
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*
6.Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion".
Ming-Yi ZHAO ; Rong HUANG ; Rong GUI ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):18-25
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
7.Risk factors and construction of a risk prediction model for readmission due to hyperbilirubinemia in neonates with ABO hemolytic disease of the newborn.
Pei-Xian YUE ; Hong-Ling CAO ; Rong LI
Chinese Journal of Contemporary Pediatrics 2025;27(7):834-841
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*
8.Clinical and immunological features for early differentiation between primary immune thrombocytopenia and connective tissue disease in children.
Fu-Rong KANG ; Mei YAN ; Ying-Bin YUE ; Hailiguli NURIDDIN ; Yong-Feng CHENG ; Yu LIU
Chinese Journal of Contemporary Pediatrics 2025;27(8):974-981
OBJECTIVES:
To investigate the clinical and immunological features of children with primary immune thrombocytopenia (pITP) or connective tissue disease (CTD) with thrombocytopenia as the initial manifestation at initial diagnosis, and to provide a basis for early differentiation.
METHODS:
A retrospective study was performed on 236 children with pITP (pITP group) or CTD with thrombocytopenia as the initial manifestation (CTD-TP group) who were admitted from January 2019 to August 2024. Clinical and immunological indicators were compared between the two groups to identify potential influencing factors for early differentiation and their discriminative validity.
RESULTS:
Compared with the pITP group, the CTD-TP group had a significantly older age of onset and significantly lower leukocyte count, eosinophil count, lymphocyte count, and complement C4 level (P<0.05), as well as significantly higher levels of C-reactive protein, IgE, and IgM (P<0.05). The logistic regression analysis showed that age, IgE, IgM, total B cells, and complement C4 were predictive factors for early differentiation between pITP and CTD-TP (P<0.05). The receiver operating characteristic curve analysis showed that a combination of these five factors had a good discriminative validity, with an area under the curve of 0.944. The correlation analysis showed a negative correlation between IgG and platelet count in the pITP group (rs=-0.363, P<0.05) and a positive correlation between NK cells and platelet count in the CTD-TP group (rs=0.713, P<0.05).
CONCLUSIONS
There is heterogeneity in the clinical and immunological indicators between children with pITP and CTD-TP at initial diagnosis, and these research findings can help with the early differentiation between the two diseases.
Purpura, Thrombocytopenic, Idiopathic/immunology*
;
Diagnosis, Differential
;
Connective Tissue Diseases/immunology*
;
Retrospective Studies
;
Early Diagnosis
;
Age of Onset
;
Leukocyte Count
;
Complement C4/immunology*
;
C-Reactive Protein/immunology*
;
Immunoglobulin E/immunology*
;
Immunoglobulin M/immunology*
;
Humans
;
Male
;
Female
;
Infant
;
Child, Preschool
;
Child
;
Adolescent
;
Biomarkers/blood*
9.Causal relationship between Helicobacter pylori infection and childhood immune thrombocytopenia and influencing factors for prognosis.
Xiao-Yang ZHOU ; Mei YAN ; Ying-Bin YUE ; Hailigulli NURIDDIN ; Xue-Mei WANG ; Yong-Feng CHENG ; Chun-Can WU ; Yu LIU
Chinese Journal of Contemporary Pediatrics 2025;27(9):1105-1112
OBJECTIVES:
To investigate the causal relationship between Helicobacter pylori (Hp) infection and immune thrombocytopenia (ITP) using Mendelian randomization (MR), as well as the association between Hp infection and chronic ITP (cITP) through a clinical study.
METHODS:
The datasets from genome-wide association studies were used to select the single nucleotide polymorphism loci significantly associated with Hp infection as genetic instrumental variables. The MR analysis model was used to investigate the causal relationship between ITP and Hp infection. A retrospective analysis was conducted on the medical data of 316 children with newly diagnosed ITP at the First Affiliated Hospital of Xinjiang Medical University from January 2020 to December 2023. The children were followed up for 1 year, and a multivariate logistic regression analysis was used to investigate the risk factors for cITP.
RESULTS:
The inverse variance weighted analysis revealed that Hp infection was significantly associated with an increased risk of ITP (OR=1.280, 95%CI: 1.098-1.492, P=0.002). There was no heterogeneity or pleiotropy in this MR study (P>0.05), and the model was stable. The "leave-one-out" sensitivity analysis verified the reliability of the results. The multivariate logistic regression analysis demonstrated that Hp infection was an independent risk factor for progression to cITP (OR=7.916, 95%CI: 3.327-18.832, P<0.001).
CONCLUSIONS
Hp infection is a risk factor for the onset of ITP and is an independent risk factor for cITP in children.
Humans
;
Helicobacter Infections/complications*
;
Purpura, Thrombocytopenic, Idiopathic/etiology*
;
Child
;
Male
;
Female
;
Helicobacter pylori
;
Prognosis
;
Child, Preschool
;
Logistic Models
;
Retrospective Studies
;
Risk Factors
;
Polymorphism, Single Nucleotide
;
Adolescent
;
Infant
10.Application of umbilical cord mesenchymal stem cells in the treatment of severe immune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation in children.
Bo ZHANG ; Zuo LUAN ; Xiang-Feng TANG ; Nan-Hai WU
Chinese Journal of Contemporary Pediatrics 2025;27(9):1128-1133
This report describes two cases of severe immune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with umbilical cord mesenchymal stem cells (UC-MSCs). Case 1 was a child with severe aplastic anemia who underwent haploidentical bone marrow and peripheral blood HSCT, with a chimerism rate of 99.8% on day +25 and severe immune-mediated thrombocytopenia on day +60. After intravenous immunoglobulin (IVIG) pulse therapy, platelet count increased temporarily but then decreased, while cyclosporine, methylprednisolone, and rituximab had a poor therapeutic effect. Case 2 was a child with Gaucher's disease who underwent unrelated umbilical cord blood HSCT, with a chimerism rate of 96.35% on day +41 and severe immune-mediated thrombocytopenia on day +153. After three sessions of IVIG pulse therapy, the platelet count increased initially but subsequently decreased. Therapies with dexamethasone, prednisone, cyclosporine, and recombinant human thrombopoietin also yielded a poor response. Both children received three sessions of UC-MSCs infusion, and platelet counts increased and were subsequently maintained within the normal range. Case 1 has been followed up for 10 years and remains in disease-free survival. UC-MSCs infusion may be effective for severe immune-mediated thrombocytopenia that is unresponsive to first- and second-line therapies after HSCT and could potentially improve the quality of life and disease-free survival rate.
Child
;
Humans
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Mesenchymal Stem Cell Transplantation
;
Purpura, Thrombocytopenic, Idiopathic/etiology*
;
Thrombocytopenia/therapy*
;
Transplantation, Homologous
;
Umbilical Cord/cytology*


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