Humans ; Anemia, Aplastic ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Immunophenotyping

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.
Humans ; Mutation ; Elliptocytosis, Hereditary/metabolism* ; Erythrocyte Membrane/metabolism* ; Exons ; High-Throughput Nucleotide Sequencing ; Spherocytosis, Hereditary/metabolism*

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/epidemiology* ; Sucrose/therapeutic use* ; Ferric Compounds/therapeutic use* ; Retrospective Studies ; Iron/therapeutic use* ; Hemoglobins/therapeutic use*

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.
Bone Marrow ; Erythropoiesis ; Humans ; Reticulocyte Count ; Reticulocytes ; Spherocytosis, Hereditary

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).
Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum/therapeutic use* ; Cyclosporine/therapeutic use* ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use* ; Prognosis ; Receptors, Transferrin/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.
Anemia, Aplastic/drug therapy* ; Animals ; Antilymphocyte Serum/therapeutic use* ; Cyclosporine/therapeutic use* ; Female ; Humans ; Immunoglobulins/therapeutic use* ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use* ; Male ; Swine ; T-Lymphocytes ; Treatment Outcome

OBJECTIVE: To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST. METHODS: The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed. RESULTS: There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3 CONCLUSION The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.
Anemia, Aplastic ; Humans ; Immunosuppression ; Immunosuppressive Agents/therapeutic use* ; Lymphocyte Subsets ; Retrospective Studies

Objective: To analyze the prognostic factors of transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients treated with cyclosporine A (CsA) and androgen. Methods: Clinical data of 77 consecutive TD-NSAA patients treated with CsA and androgen were retrospectively analyzed between 2010 and 2013. We obtained clinical manifestations and baseline parameters of routine blood test from responders, and compared those with non-responders. All data were analyzed by univariate analysis and multivariate analysis. Results: In 77 patients, there were 43 (55.8%) patients achieved hematological response after 6 months'treatment, and 53 (68.8%) patients got response after 12 months. Univariate analysis showed that platelets baseline was the only factor related to hematological response [19 (6-61) ×10(9)/L vs 13.5 (5-45) ×10(9)/L, P=0.001] after 6 months therapy. After 12 months, the statistical differences were maintained, which were platelets baseline [18 (6-61) ×10(9)/L vs 10.5 (5-45) ×10(9)/L, P<0.001], absolute reticulocytes [0.03 (0.01-0.06) ×10(12)/L vs 0.029 (0.02-0.06) ×10(12)/L, P=0.043], transfusion-dependent of platelet (P=0.007) , transfusion-dependent of platelet and erythrocyte (P=0.012) . Multivariate analysis showed that platelets baseline could be an independent prognostic factor of hematological response (P=0.010 or 0.009) . Cutoff value of platelets by receiver operating characteristic curve was 15.5×10(9)/L. Conclusion: Baseline of higher platelets, higher reticulocyte, and no transfusion dependence of platelet are favorable prognostic factors. When platelets baseline is higher than 15.5×10(9)/L, CsA and androgen regimen is rational.
Androgens/therapeutic use* ; Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum ; Cyclosporine/therapeutic use* ; Drug Combinations ; Humans ; Immunosuppressive Agents ; Prognosis ; Retrospective Studies ; Treatment Outcome

Objective The aim is to analyze the spatial epidemiological characteristics for human infection with avian influenza H7N9 in Fujian Province, so as to provide scientific evidence for developing and adjusting related control strategies. Methods The epidemiological data of human infection with H7N9 avian influenza in Fujian Province, from 2013 to 2017 was analyzed by SAS 9.2, ArcGIS 10.3 and SaTScan 9.4 software.Results There were a total of 108 cases and 28 deaths reported in Fujian Province, up to December 31, 2017. The case fatality rate was 25.93%.96.30% of cases were sporadic. There were more incidences in winters and springs, more incidences in rural areas. The global spatial autocorrelation and high/low clustering analysis indicated that clusters at the county level were in the shore areas (Z=3.74, P<0.001; Z=5.26, P<0.001). The cities of Changle, Fuqing, Jinjiang and Siming were the high-high clustered areas and local hot-points. There were two clusters, from December 2014 to March 2015, the most likely cluster regions was centered around Zhangpu County with a radius of 63.04 km (RR=4.72, LLR=11.41, P<0.001). The secondary cluster regions was centered around Fuqing City with a radius of 81.98 km (RR=4.07, LLR=7.96, P=0.037). Conclusions Human infection with avian influenza H7N9 in Fujian Province is spatially and temporally clustered. The measures of prevention and control should be focused on high incidence seasons and key regions, and the surveillance of etiology should be strengthened.

Anemia, Hemolytic, Congenital ; Humans ; Ion Channels/genetics* ; Mutation