患儿 男，5岁，因反复出血5年余加重3个月入院，以消化道出血为首发表现，凝血酶原时间延长，凝血因子Ⅶ促凝活性降低，F7基因双杂合子突变（7号内含子 c.681+1 G>T来自父亲，9号外显子c.1256 C>T来自母亲），确诊为遗传性凝血因子Ⅶ缺乏症（重型）。患儿确诊后经历反复出血，第15个暴露日检测出凝血因子Ⅶ 抑制物2.05 BU/ml，确诊为遗传性凝血因子Ⅶ缺乏症（重型）合并低滴度凝血因子Ⅶ 抑制物，药物控制出血效果差，予利妥昔单抗输注，连续4周后抑制物转阴，之后预防治疗，随访40周患儿未再出血，抑制物未复发。.

例1，男，6岁，因间断鼻衄4年余入院，血常规提示血小板减少，低浓度瑞斯脱霉素诱导血小板聚集阳性，血管性血友病因子（vWF）基因c.3916C>T（p.R1306 W）杂合错义突变。例2，女，8日龄，因血小板减少5 d入院，予以人免疫球蛋白输注无效，低浓度瑞斯脱霉素诱导血小板聚集阳性，vWF基因c.3946G>A（p.V1316M）杂合错义突变，为自发突变。例3，因间断鼻衄3年余入院，血常规提示血小板减少，外院予丙种球蛋白、糖皮质激素治疗效果不佳，低浓度瑞斯脱霉素诱导血小板聚集阳性，vWF基因c.3946G>A（p.V1316M）杂合错义突变，为自发突变。3例患儿均确诊为血管性血友病。例1及例3应用含血管性血友病因子的人血源性凝血因子Ⅷ可止血，血小板可升至正常。

Objective:To explore the new mechanism of liver fibrosis through D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced necroptosis as an entry point to inhibit lethal injury.Methods:The carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was established. At 6 weeks of fibrosis, the mice were challenged with a lethal dose of D-GalN/LPS, and the normal mice treated with the same treatment were used as the control. The experiment was divided into four groups: control group (Control), acute injury group (D-GalN/LPS), liver fibrosis group (Fib), and liver fibrosis + acute challenge group (Fib + D-GalN/LPS). Quantitative PCR and immunofluorescence were used to analyze the expression of necroptosis key signal molecules RIPK1, RIPK3, MLKL and/or P-MLKL in each group. Normal mice were treated with inhibitors targeting key signaling molecules of necroptosis, and then given an acute challenge. The inhibitory effect of D-GalN/LPS-induced-necroptosis on acute liver injury was evaluated according to the changes in transaminase levels and liver histology. Liver fibrosis spontaneous ablation model was established, and then acute challenge was given. Necroptosis key signal molecules expression was analyzed in liver tissue of mice in each group and compared by immunohistochemistry. The differences between groups were compared with t-test or analysis of variance.Results:Quantitative PCR and immunofluorescence assays result showed that D-GalN/LPS-induced significant upregulation of RIPK1, RIPK3, MLKL and/or P-MLKL. Necroptosis key signal molecules inhibition had significantly reduced D-GalN/LPS-induced liver injury, as manifested by markedly reduced serum ALT and AST levels with improvement in liver histology. Necroptosis signaling molecules expression was significantly inhibited in fibrotic livers even under acute challenge conditions. Additionally, liver fibrosis with gradual attenuation of fibrotic ablation had inhibited D-GalN/LPS-induced necroptosis.Conclusion:Liver fibrosis may protect mice from acute lethal challenge injury by inhibiting D-GalN/LPS-induced necroptosis.

Objective: To compare the efficacy and safety of 2 low-dose rituximab regimens in the treatment of children with primary immune thrombocytopenia (ITP). Methods: A total of 90 ITP children admitted to the Hematology Oncology Center of Beijing Children's Hospital from January 2018 to March 2021 were enrolled in this prospective cohort study. In the single-dose group, rituximab was given with a single dose of 375 mg/m2 (maximum dose 600 mg). In the 4-dose group, rituximab was given with a dose of 100 mg weekly (if body weight of the patient ≥ 30 kg, increase dosage to 200 mg weekly) for 4 weeks. Wilcoxon Mann-Whitney test, Chi-square test and Fisher's exact test were used to analyze the difference in efficacy, safety and treatment burden between two groups. Results: Among the 90 children, 41 were male and 49 were female, and the age of medication was 6.8 (4.1,10.0) years. There were 27 cases in the single-dose group and 63 cases in the 4-dose group.There were no significant differences in overall response rate, complete response rate and partial response rate between the single-dose group and 4-dose group (41% (11/27) vs. 33% (21/63), 26% (7/27) vs. 19% (12/63), 15% (4/27) vs. 14%(9/63), χ2=0.45, 0.54, 0.00, all P>0.05). The single-dose group was earlier to get overall response than the 4-dose group (1 (1, 1) vs. 3 (2, 6) weeks, Z=-3.24, P=0.001). There were no significant differences in the sustained response rate, the overall response rate in 1 year, the complete response rate in 1 year, and the partial response rate in 1 year between the single-dose group and the 4-dose group (33% (9/27) vs. 30% (19/63), 30% (8/27) vs. 24% (15/63), 19% (5/27) vs. 14% (9/63), 11% (3/27) vs. 10% (6/63), χ2=0.09, 0.34, 0.04, 0.00, all P>0.05). There were no significant differences in the duration of overall response, recurrence rate within half a year and one year, recurrence time and rate of adverse events between the single-dose group and 4-dose group (all P>0.05). The number of hospitalizations, the duration of hospital stays and the dosage of the single-dose group were significantly lower than those of the 4-dose group (1 (1, 1) vs. 4 (4, 4) times, 5 (4, 7) vs. 8 (5, 8) d, 400 (250, 500) vs. 400 (400, 800) mg, Z=-8.67, -3.03, -4.05, all P<0.05). Conclusions: The single-dose rituximab regimen is comparable to 4-dose rituximab regimen in effectiveness and safety for treatment of children ITP, but more economical and convenient. The single-dose rituximab regimen is more suitable for the second-line treatment of children ITP.

Background: Background: Personalized Personalized prophylaxies for moderate and severe hemophilia A and B are based on personal pharmacokenetics (PK), half-life(T 1/2 ). While classical method for personal PK needs multiple blood collections, at least 5 points collections for children and 11points for adults, and expensive for testing and leads low compliance. Popular PK based on pupolar data can have a less blood collections but a rough data(range) is recommended for reference. One-chamber model may also have a less blood collection 2-3 collections for PK detection. Aims: Aims: Objective: Objective: To analyze and compare the half-life (T 1/2 ) results of Factor VIII (FVIII) calculated by modified one-chamber model by "CAI's" hemophilia pharmacokinetic calculation tool and WinNolin software (five-point sampling), non-av model, and to explore the reliability and clinical application value of "CAI's" hemophilia pharmacokinetic calculation tool. Methods: Methods: A total of 30 patients with moderate and severe hemophilia A were treated with FVIII (50IU/Kg) after the 72-hour elution period. Peripheral blood samples were collected at five time points before and after FVIII calculation tool, and the were compared of was Summary/Conclusion: Summary/Conclusion: 1. Compared with the T 1/2 results by WinNolin's method and modified ond-chambor modle (”CAI’s” tool), the most consistency of T 1/2 of blood sampling was 9h~48h. However, for those T 1/2 short than 7~8hs, the detection time should be adjusted (the later blood sample taking should be adjust to earlier); 2. Nearly 3/4 of the 30 cases, the T 1/2 results fluctuated among three periods (9h~24h, 24h~48h, 9h~48h) in one case, suggesting a standardized test procedures such as specimen collection, sample transportation and detection ect needs to set up to ensure the stability and reliability of test results. 3. The classical pharmacokinetic test requires at least 5 points of blood sample collections, which is difficult to be popularized and applied in clinical practice. If a standardized and standardized testing process is established, the one-chamber model method is relatively simple and easy to be accepted and popularized by patients.

Objective: To explore the clinical features and points of diagnosis and treatment for congenital thrombotic thrombocytopenic purpura (TTP) in children. Methods: The clinical manifestations, laboratory tests, genetic analysis and treatments of 5 children with congenital TTP hospitalized in Beijing Children's Hospital, Capital Medical University from February 2015 to July 2017 were analyzed retrospectively. Results: Among the 5 children with congenital TTP diagnosed by genetic monitoring and enzymology, there were 1 male and 4 females, 3 cases had suspicious positive family history, the age of onset was several hours after birth (range several hours after birth to 28 months). The main clinical manifestations were recurrent moderate to severe thrombocytopenia in 5 cases, mild to moderate hemolytic anemia in 4 cases, proteinuria or hematuria in 2 cases, and nervous system involvement in 1 case. The recurrence time was 1.5 (range 1.0 to 5.0) times per year and most of the inducing factors were respiratory and (or) digestive tract infections. Laboratory test showed that ADMATS13 enzyme activity were 0 in 4 cases, the enzyme activity was 100% in 1 case due to plasma infusion before examination. ADMATS13 enzyme antibody detection of all 5 cases were negative. Genetic analysis of all 5 children showed complex heterozygous mutations at different loci of ADAMTS13 gene, among which 8 loci were previously unreported, details are as follows: missense mutations in 4 cases (c.1564T>C(p.522C>R), c.1510G>T(p.504D>Y), c.4154A>C(p.1385Q>P) and c.G3854C (P.R1285P)); frameshift mutations in 3 cases(c.2875_2876insT (p.959Lfs29), c.2362_2363delGG (p.788G>Gfs56) and c.1335delC (p.F445fs)), shear mutation in one case(IVS21+1A>G). The patients in the acute phase were all treated with fresh frozen plasma infusion (10 ml/(kg·d)), continuous application for 7-14 days). Platelets gradually returned to normal and clinical symptoms improved. The follow-up time was 27 months (range 11-35 months). All the children survived, among whom 2 cases were treated with prophylaxis and monitoring platelet stability above 200×10(9)/L, 3 cases were treated on-demand only when platelet decreased and monitoring platelet stability above 100×10(9)/L. Conclusions: The main clinical manifestation of congenital TTP is recurrent thrombocytopenia with or without hemolytic anemia. The key point of treatment is plasma infusion. Genetic testing is helpful for early diagnosis.

Objective To detect the arthropathies on no bleeding history joints in pre-school hemophilia A children in order to provide evidence for further prevention and control of joint disease in children with hemophilia A. Methods This study was a cross-sectional study based on China Hemophilia Individualized prophylaxis study (CHIPS). The basic data of outpatients with hemophilia in Beijing Children's Hospital and Chengdu Women's and Children's Central Hospital between August 2016 and June 2017 were collected and a three-month follow-up was conducted. The target joints (six joints of bilateral elbows, knees and ankles) of thirty-four children aged 1-7 years old with severe hemophilia A were examined by ultrasound, X-ray and joint function examination (4-7 years old, hemophilia joint health score (HJHS)). To find out whether there are arthropathies in patient's joints with no bleeding history and analyzethe relevant factors by chi-square test, rank sum test and other statistical methods. Results There were 32 analyzable cases with 112 no-bleeding history target joints, 42.9％(48/112) were elbow joints. Arthropathies were revealed in 34.8％(39/112) of them by joint structural and functional examination and 46.2％(18/39) were ankles (χ2=8.379,P=0.015). Ultrasound showed abnormalities in 18.3％(20/109) joints, X-ray showed abnormalities in 3.8％(3/79) joints and HJHS showed abnormalities in 25.3％(20/79) joints. There was no correlation between ultrasound and HJHS (r=0.015 ,P=0.895), no correlation was found between X-ray and HJHS (r=-0.101,P=0.390)either, which suggested that joint structural and functional examination could not replace each other. The related risk factors of arthropathies in this group were >4.91 years old (OR=3.917, 95％CI: 1.610-9.528) and combining with target joint (OR=3.530, 95％CI: 1.316-9.465). Conclusions Detecting the joint structure and function on no bleeding history joints in pre-school hemophilia A children could reveal the arthropathies and majority of them were ankle arthropathies. Joint structural and functional examinations could not replace each other. For patients more than 5 years old and those with target joints, the joints with no complaint of bleeding should be examined regularly to reveal the arthropathies in time.