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Introducción: los medicamentos antitiroideos son una de las alternativas terapéuticas en el tratamiento de la enfermedad de Graves. Sin embargo, pueden generar efectos adversos severos poco frecuentes en el plano hematológico, como la anemia aplásica, la cual se ha asociado con altas dosis de estos medicamentos, aunque con reversión de esta afección ante el retiro del medicamento. Descripción del caso: mujer de 38 años con antecedente de enfermedad de Graves en tratamiento con metimazol, quien consultó por síntomas como epistaxis anterior de difícil control, petequias, astenia e hiporexia. Se documentó pancitopenia en el hemo-grama, con posterior hallazgo en biopsia de médula ósea de aplasia medular, sin respuesta ante el retiro del metimazol y soporte transfusional. Posteriormente, la paciente falleció. Conclusión: la presentación de aplasia medular asociada con metimazol es poco común y se relaciona con altas dosis de este medicamento. En la mayoría de casos, el retiro de este agente genera recuperación clínica y celular. No obstante, en algu-nos pacientes persiste el compromiso hematológico que va desde importantes repercusiones clínicas hasta desenlaces fatales. Por lo tanto, el presente caso busca hace hincapié en la importancia de vigilar este efecto adverso ante el inicio de esta medicación
Introduction: Antithyroid drugs are one of the therapeutic alternatives in the treatment of Graves' dis-ease. However, it can generate severe but infrequent adverse effects at the hematological level, such as aplastic anemia, which has been associated with high doses of these drugs, although with reversal of this hematological condition when the drug is withdrawn. Case description: A 38-year-old woman with a his-tory of Graves' disease treated with methimazole, who consult for symptoms such as anterior epistaxis, petechiae, asthenia, and hyporexia. Pancytopenia is documented in the blood count, with a subsequent finding of bone marrow aplasia in bone marrow biopsy, without response to withdrawal of Methimazole and transfusion support. The patient subsequently died. Conclusion: The methimazole-associated bone marrow aplasia is uncommon and it Ìs associated with high doses of methimazole, in most cases with-drawal of methimazole leads to clinical and cellular recovery. However, in some patients hematological involvement persists with significant clinical repercussions up to fatal outcomes. Therefore, this case seeks to highlight the importance of monitoring for this adverse effect before starting this medication
Introdução: as drogas antitireoidianas são uma das alternativas terapêuticas no tratamento da doença de Graves. No entanto, pode causar efeitos adversos graves, mas infrequentes, no nível hematológico, como a anemia aplástica, que tem sido associada a altas doses desses medicamentos, embora com rever-são desse quadro hematológico quando a droga é retirada. Descrição do caso: mulher de 38 anos com história de doença de Graves tratada com metimazol, que consultou por sintomas como epistaxe ante-rior de difícil controle, petéquias, astenia e hiporexia. A pancitopenia é documentada no hemograma, com achado posterior de aplasia da medula óssea na biópsia da medula óssea, sem resposta à retirada do metimazol e suporte transfusional. O doente faleceu posteriormente. Conclusão: a apresentação de aplasia da medula óssea associada ao metimazol é pouco frequente em associação com doses elevadas de metimazol. Na maioria dos casos, a retirada do metimazol conduz à recuperação clínica e celular. No entanto, nalguns doentes, o envolvimento hematológico persiste com repercussões clínicas significati-vas, podendo mesmo ocorrer desfechos fatais. Assim, o presente caso pretende realçar a importância da monitorização deste efeito adverso antes de iniciar esta medicação
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Objective To investigate the nutritional status in patients with aplastic anemia (AA), and to analyze the influencing factors. Methods A retrospective analysis was performed on the clinical data of 152 patients with AA admitted to West China Hospital between March 2019 and March 2022. The nutritional status of all patients was screened by Nutritional Risk Screening 2002 (NRS2002). According to the screening criteria, the patients were divided into control group (46 cases, total NRS2002 score 0.05). The proportion of SAA cases in the malnutrition risk group was significantly higher than that in the control group. The levels of Alb and UIBC in the malnutrition risk group were significantly lower than those in the control group, while the levels of SF, SI and TSAT were higher than those in the control group. In addition, the levels of SF, SI and TSAT in SAA patients were higher than those in NSAA group (P<0.05). Logistic regression analysis showed that high levels of SF, SI and TSAT, and high proportion of SAA cases were risk factors of malnutrition in AA patients (P<0.05). The incidence of adverse prognosis in the malnutrition risk group was significantly higher than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Patients with AA have a higher risk of malnutrition, and high levels of SF, SI and TSAT are risk factors for malnutrition. The greater the risk of malnutrition, the more severe the poor prognosis.
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ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3+ human leukocyte antigen-DR （HLA-DR）+ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8+≥50%， and CD3+HLA-DR+≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8+≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3+HLA-DR+<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3+HLA-DR+<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3+HLA-DR+ levels and increased proportion of patients with Th1<12%， CD4+≥6%， and CD3+HLA-DR+<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3+HLA-DR+<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3+HLA-DR+≥9%， especially those with CD8+≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3+HLA-DR+<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4+≥6%， especially those with CD3+HLA-DR+<5%.
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Objective:To explore the values of peripheral blood neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) in the differential diagnosis of cytopenic diseases.Methods:A retrospective case series study was conducted. The clinical data of 105 newly diagnosed patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) or primary immune thrombocytopenia (ITP) who were admitted to Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from August 2017 to November 2020 were retrospectively analyzed. There were 42 patients with MDS (13 cases of hypoplastic MDS, 23 cases of non-hypoplastic MDS, 6 cases could not be classified), 42 patients with ITP, and 21 patients with AA. The peripheral blood lymphocyte count, neutrophil count, monocyte count, and platelet count of each untreated patient at the time of initial diagnosis were recorded, the NLR, MLR and PLR were calculated, and the differences of NLR, MLR and PLR among different diseases were compared; the differential diagnostic values of each index for AA, MDS and ITP were evaluated by using the receiver operating characteristic (ROC) curve.Results:The NLR [ M (IQR)] in ITP, AA and MDS groups was 3.08 (2.42), 0.57 (0.66) and 0.83 (1.27) ( χ2 = 56.84, P<0.001), the MLR was 0.26 (0.15), 0.13 (0.14) and 0.20 (0.33) ( χ2 = 18.71, P<0.001), and the PLR was 5.12 (9.97), 8.67 (14.21) and 49.32 (78.66) ( χ2 = 47.07, P<0.001). The best cut-off value of NLR for distinguishing ITP from MDS was 1.757, and the area under the curve (AUC) was 0.833 (95% CI: 0.811-0.955), while the sensitivity and specificity were 78.6% and 83.3%, respectively. The best cut-off value of NLR for distinguishing ITP from AA was 1.350, and the AUC was 0.993 (95% CI: 0.981-1.000), while the sensitivity and specificity were both 95.2%. The best cut-off value of PLR for distinguishing AA from MDS was 23.542, and the AUC was 0.841 (95% CI: 0.739-0.944), while the sensitivity and specificity were 85.7% and 73.8%, respectively. The best cut-off value of NLR for distinguishing AA from MDS was 0.764, and the AUC was 0.687 (95% CI: 0.556-0.891), while the sensitivity and specificity were 71.4% and 64.3%, respectively. The best cut-off value of MLR for distinguishing AA from MDS was 0.148, and the AUC was 0.736 (95% CI: 0.614-0.859), while the sensitivity and specificity were both 71.4%. Conclusions:The peripheral blood NLR, MLR and PLR have certain reference values for differential diagnosis of AA, MDS and ITP.
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The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.
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Objective:To explore the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and readmission in patients with chronic aplastic anemia (AA).Methods:A total of 105 patients with chronic AA who were hospitalized at the Fuyang People′s Hospital Affiliated to Anhui Medical University from January 2020 to December 2022 were selected. The serum 25(OH)D level was measured using chemiluminescence method, and it was divided into low value group and high value group based on the average value. We compared the clinical data differences between two groups of patients, used logistic multivariate analysis to identify the risk factors for readmission in chronic AA patients, and used the Kaplan Meier method to plot curves to compare the differences in readmission rates and readmission intervals between the two groups.Results:The difference in the interval between readmission between patients in the low value group (<19.39 ng/ml) and those in the high value group (≥19.39 ng/ml) was statistically significant [(2.61±1.03)months vs (3.27±1.32)months, P<0.05]. A higher level of serum 25(OH)D was a protective factor in reducing the risk of readmission ( OR: 0.739; 95% CI: 0.569-0.962) and prolonging the interval between readmission (Log Rank=0.004, Breslow=0.01, Tarone-Ware=0.005; P<0.05) in chronic patients, while long course of illness was a risk factor for readmission ( OR=3.432, P=0.006). Patients in the low value group who had accumulated the use of vitamin D supplements for ≥3 weeks had a significantly longer interval between readmission ( P<0.001). Conclusions:Abnormal reduction of serum 25(OH)D levels can shorten the interval between readmission and increase the risk of readmission in chronic AA patients.
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ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia， and provide prognosis indicators for the treatment of aplastic anemia （AA） with kidney-tonifying therapy in traditional Chinese medicine （TCM） combined with western medicine. MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment， the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age， sex， disease severity （including severe aplastic anemia and non-severe aplastic anemia）， course of disease， degree of bone marrow nucleated cell proliferation， baseline hemogram levels ［including white blood cell count （WBC）， absolute neutrophil count （ANC）， hemoglobin （HGB）， platelets （PLT）， and reticulocytes （RET）］， T lymphocytes subsets， and the expression levels of T-box transcription factor （T-bet） and GATA-binding protein-3 （GATA-3） were compared between the two groups before treatment. ResultThe proportions of patients within the age ranges of ［20， 40） and ［60， 80） were higher in the 4-month effective group （P<0.05）. The sex， disease severity， course of disease， and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB， WBC， ANC， and PLT than the 4-month ineffective group （P<0.05）， and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time， while other indicators did not affect the onset time. The receiver operating characteristic （ROC） curve was established to analyze the value of PLT level before treatment for predicting the onset time， and the area under the curve was 0.691. With the critical value of 40.5×109/L， the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893， respectively. The two groups of patients were graded according to age ｛（14， 20）， ［20， 40）， ［40， 60）， and ［60， 80）｝ and PLT level before treatment （PLT<40×109/L， PLT≥40×109/L）. The proportion of the patients with PLT≥40×109/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group （P<0.05）. The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment （P<0.05）. The levels of Th1 cells， Th2 cells， CD4+ T cells， and CD8+ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment （P<0.05）， while the expression level of GATA-3 showed no significant difference between the two groups before treatment. ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of ［20， 40） or ［40， 60）， with higher levels of HGB， WBC， ANC， and PLT （especially those with PLT≥40×109/L）， lower level of total T lymphocytes， or higher T-bet expression level before treatment.
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ObjectiveTo explore the clinical effect of kidney-tonifying and blood-generating method and qi-promoting and blood-nourishing method combined with western medicine on the treatment of aplastic anemia and the characteristics of blood routine recovery， and to explore a new phased treatment model for aplastic anemia. MethodThis study was based on a prospective， multicenter， double-blind， and randomized controlled clinical trial. Patients with aplastic anemia from 19 centers were analyzed and divided into a kidney-tonifying and blood-generating group and a Qi-promoting and blood-nourishing group， which were treated with traditional Chinese medicine （TCM） combined with western medicine. The clinical effect and the changes in blood routine in each group during treatment were evaluated. ResultDuring the observation period， 375 cases of aplastic anemia were included in two groups， and TCM syndrome differentiation conformed these cases as Qi-deficiency type and both Qi and blood-deficiency type. These cases were randomly divided into two groups， including 184 in the kidney-tonifying and blood-generating group and 191 in the Qi-promoting and blood-nourishing group， being treated by kidney-tonifying and blood-generating granules and Qi-promoting and blood-nourishing granules， respectively， and combined oral androgen and ciclosporin soft capsules. The treatment lasted for six months and was divided into three stages. Visits were conducted from the beginning of the treatment to the end of the first， fourth， and sixth months. The curative effect was evaluated six months later. The total effective rate of the kidney-tonifying and blood-generating group was 86.4% （159/184）， which was significantly better than that of the Qi-promoting and blood-nourishing group ［68.6% （131/191）， P<0.01）］. The results of the percentage quartile of blood cell growth in each stage of the 2 groups were analyzed. The hemoglobin concentration and platelet count of the patients in the kidney-invigorating blood group continued to increase after treatment, and significantly increased in the second and third stages compared with the first stage (P<0.05). The increase of reticulocyte count was most significant in the first stage of treatment (P<0.05). The reticulocyte count in supplementing Qi and nourishing blood group increased significantly in the first and second stages of treatment (P<0.05). The other observation indicators increased at each stage, but there was no statistical difference in the growth rate. The effects of the two groups were compared by stages. In the second stage of treatment, the increase of hemoglobin concentration in the kidney-invigorating blood group was better than that in the supplementing Qi-nourishing blood group (P<0.05). The increase of platelet count and red blood cell count in supplementing Qi and nourishing blood group was greater (P<0.05). In the third stage of treatment, the increase of hemoglobin concentration in the bushen Shengxue group was more significant (P<0.05). ConclusionThe overall effective rate of the kidney-tonifying and blood-generating method in the treatment of aplastic anemia is better than that of the Qi-promoting and blood-nourishing method， with significant effects and safety. This study has proposed a three-stage early treatment mode for aplastic anemia. The first and third stages (0-1, 5-6 months) were mainly treated by invigorating kidney and generating blood. In the second stage of treatment (2-4 months), invigorating kidney and generating blood combined with invigorating Qi and nourishing blood were adopted. It may be closer to the actual clinical treatment response and objective rule changes of aplastic anemia.
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ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the patients with aplastic anemia （AA）. MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A （CsA） and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， mTOR， phosphorylated （p）-mTOR， Akt， p-Akt， PI3K， and p-PI3K， and real-time polymerase chain reaction （PCR） to determine the mRNA levels of LC3， mTOR， Akt， and PI3K. ResultIn the AA group， the treatment was completed in 29 patients， and the total response rate was 51.72% （15/29）. ① The AA group showed lower levels of white blood cell （WBC）， hemoglobin （HGB）， platelet （PLT）， and absolute neutrophil count （ANC） in the peripheral blood （P<0.01） and lower number of intracellular autophagosomes than the control group before treatment. Moreover， the AA group showed lower mRNA level of LC3 （P<0.01） and protein levels of LC3Ⅰ and LC3Ⅱ （P<0.01） and higher mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and protein levels of Akt， p-Akt， PI3K， p-PI3K， mTOR， and p-mTOR （P<0.01） than the control group. ② In AA group， the levels of HGB and PLT elevated （P<0.05） and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover， the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated （P<0.01）， the mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and the protein levels of Akt， p-PI3K （P<0.01）， p-Akt， PI3K， mTOR， p-mTOR （P<0.05） were down-regulated after treatment. ConclusionAA patients show lower autophagy levels， while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.
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OBJECTIVE To systematically evaluate the efficacy and safety of eltrombopag combined with immunosuppressive therapy （IST） for severe aplastic anemia （SAA）， and to provide evidence-based basis for clinical treatment of SAA. METHODS Retrieved from PubMed， Embase， Cochrane Library， ClinicalTrials.gov， VIP， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about eltrombopag combined with IST （trial group） versus IST alone （control group） were collected from the inception to May 2023. After data extraction and quality evaluation （Cochrane manual 5.1.0） of included studies， meta-analysis， subgroup analysis， sensitivity analysis and publication bias analysis were performed by using RevMan 5.4 software. RESULTS A total of 12 studies were screened， including 1 344 patients. Compared with control group， objective remission rate （ORR） （RR＝1.34， 95%CI was 1.06-1.69， P＝0.01） and complete response rate （CRR） （RR＝1.88， 95%CI was 1.31-2.71， P＝ 0.000 6） at 3 months， ORR （RR＝1.33，95%CI was 1.23-1.43， P＜0.000 01） and CRR （RR＝1.88，95%CI was 1.57-2.25，P＜0.000 01） at 6 months were significantly increased in trial group. There was no statistically significant difference between the two groups in ORR （RR＝0.99， 95%CI was 0.82-1.18， P＝0.88） and CRR （RR＝1.02， 95%CI was 0.78-1.34， P＝0.87） at 12 months， two-year overall survival （OS） rate （HR＝0.61， 95%CI was 0.31-1.22， P＝0.17）， two-year event-free survival （EFS） rate （HR＝0.81， 95%CI was 0.61-1.07， P＝0.14）， clone evolution rate（RR＝1.01， 95%CI was 0.51-2.00， P＝ 0.98） or the incidence of adverse drug reactions such as liver/renal insufficiency， rash （P＞0.05）. Results of subgroup analysis showed that ORR and CRR of trial group at 6 months were higher than those of the control group in RCT and the cohort study subgroups （P＜0.05）. There was no statistically significant difference in the two-year OS rate， two-year EFS rate or clone evolution rate between trial group and control group in the two subgroups （P＞0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small. CONCLUSIONS The addition of eltrombopag in the IST regimen of SAA can improve the early hematological remission rate of patients， has no significant impact on short-term survival， and will not increase the occurrence of adverse drug reactions and clonal evolution.