Eltrombopag for the treatment of primary immune thrombocytopenia in 23 pediatric patients / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of eltrombopag in the treatment of pediatric primary immune thrombocytopenia (ITP) .@*Methods@#The clinical characteristics of 23 pediatric ITP patients who received eltrombopag from May 2015 to March 2019 were retrospectively analyzed. Eltrombopag started with an initial dose of 12.5-50.0 mg/d and the maximum dose was 75.0 mg/d.@*Results@#Among 23 children, there were 11 boys and 12 girls with median age 11.0 (2.0-17.0) years. Four cases were newly diagnosed ITP, the other 8 of persistent ITP and 11 of chronic ITP. The duration of eltrombopag application ranged from 4.5 to 95 weeks (8/23 still ongoing) . The median platelet (PLT) counts at 2 weeks, 4 weeks, 3 months and the 6 months after treatment were 40 (4-170) ×109/L, 20 (4-130) ×109/L, 60 (4-110) ×109/L, and 70 (18-160) ×109/L, which were all significantly higher than that before treatment 14 (2-82) ×109/L (z=-3.440, P=0.001; z=-1.964, P=0.049; z=-4.339, P<0.001;z=-5.794, P<0.001 respectively) . The overall response rate was 60.87% (14/23 cases) . The median time to PLT count ≥30×109/L was 10.5 (3-42) days. Seven patients (30.43%) responded within the first week, and 10 cases (43.48%) achieved PLT counts ≥30×109/L within 2 weeks. All patients were divided into three groups according to the age (<6 years old, 6-12 years old, 13-17 years old) . The response rates were similar in three groups, as 33.33%, 60.00%, 85.71%, respectively. WHO bleeding scores as 0, 1, 2 were corresponded to 4, 12 and 7 patients before treatment. Patient numbers changed to 13, 7, 3 with bleeding scores 0, 1, 2 respectively after treatment (χ2=7.558, P=0.006) . Eltrombopag was well tolerated, the common adverse events included elevated transaminase (4 cases) and serum bilirubin (4 cases) ; mild nausea (1 case) , vomiting (1 case) and dizziness (1 case) . No drug withdrawal occurred due to adverse events.@*Conclusion@#Eltrombopag is safe and effective in pediatric patients with primary ITP.

Gene mutation spectrum and clinical characteristics analysis of 178 patients with essential thrombocytosis / 中华血液学杂志

Objective@#To analyze the gene mutation spectrum, clinical features, and the factors of disease progression and prognosis in patients with essential thrombocytosis (ET) .@*Methods@#A retrospective analysis was conducted on 178 newly diagnosed ET patients admitted from February 1st, 2009 to November 1st, 2018.@*Results@#Of the 178 patients, 89 were male and 89 female, and the median diagnosis age was 49.5 (3-86) years old. JAK2V617F, CALR and MPL mutations frequencies were 16.45% (1.67%-43.90%) , 40.00% (10.00%-49.15%) and 25.10% (25.00%-40.00%) , respectively. Compared with patients with CALR mutations, patients with JAK2V617F mutation had higher diagnosis age (P=0.035) , higher white blood cell count (P=0.040) , higher hemoglobin concentration (P=0.001) , and lower platelet count (P=0.002) , respectively. Of them, 47 patients (27.01%) developed thrombotic events before diagnosis, and 3 ones (1.72%) experienced thrombotic events after diagnosis. Multivariate analysis revealed age >60 years (P=0.013, OR=4.595, 95%CI 1.382-15.282) and cardiovascular risk factors (CVF) (P<0.001, OR=8.873, 95%CI 2.921-26.955) as risk factors for thrombotic events, CALR mutation (P=0.032, OR=0.126, 95%CI 0.019-0.838) as a protective factor for thrombotic events. Age >60 years (P=0.042, OR=4.045, 95%CI 1.053-15.534) was found to be a risk factor for the overall survival (OS) of ET patients. OS of age ≤60 years and age>60 years were calculated by Kaplan-Meier analysis to be (115.231±1.899) months and (83.291±4.991) months (χ2=6.406, P=0.011) , respectively.@*Conclusion@#Age>60 years and CVF were risk factors for thrombotic event. CALR mutation was a protective factor for thrombotic event. Age >60 years was a risk factor for OS in ET patients.

Prevalence and risk factors of uncontrolled allergic rhinitis / 中国耳鼻咽喉头颈外科

OBJECTIVE We used Al lergic Rhinitis Control Test (ARCT) questionnaire to evaluate the control level of allergic rhinitis, in order to get the data of prevalence rate, epidemiological characters and risk factors of uncontrolled allergic rhinitis. METHODS Patients with AR were recruited from our department and the treatment based on the Allergic Rhinitis and Its Impact on Asthma(ARIA) guidelines. Telephone interview will be taken after 2 weeks in these patients, compared to symptoms, impact on quality of life, ARCT value before and after treatment. RESULTS Among 134 patients enrolled, moderate/severe AR account for 95％. After 2 weeks of treatment, both symptom and quality of life were marked improvement(P <0.001). Patients with uncontrolled AR(26.1％) at day 15 more frequently presented higher height and weight(P <0.001), history of ear, nose, and throat(ENT) infection or antibiotics intake for respiratory infection in the last 12 months (40.4％ versus 62.9％, P =0.022), smoking (4.0％ versus 17.1％, P =0.02), and smell disturbance (10.1％ versus 25.7％, P =0.044). CONCLUSION Most of AR patients have remarkable improvements in symptom and quality of life after treatment, but 26.1％ of patients still remain uncontrolled. Smoking and nose infection are risk factors of uncontrolled AR.

The incidence and risk factors for thrombosis in primary immune thrombocytopenia / 中华血液学杂志

Objective@#To probe the incidence and risk factors for thrombosis in Chinese immune thrombocytopenia through a retrospective analysis of the inpatients referred to the Blood Disease Hospital, CAMS & PUMC.@*Methods@#A retrospective survey of 3 225 patients with ITP from October 2005 to December 2017 was performed, the clinical data of the patients with thrombosis were collected to analyze the causes, diagnosis, treatment and prognosis.@*Results@#A total of 46 patients experienced a thrombotic event with a prevalence of 1.43%(46/3 225 cases) with the median age of thrombosis as 54 years (26-83) years, the prevalence of thrombosis was 3.37% (40/1 187 cases) in>40 years old, which was significantly higher than 0.58% (6/1 030 cases) in those under 40 years old, in adults (P=0.00). There were 20 males and 26 females, there was no statistical difference in the incidence of thrombosis between males and females[1.53% (20/1 309) vs 1.36% (26/1 916), P=0.187]; The prevalence of arterial thrombosis was 1.12% (36/3 225) higher than venous thrombosis[0.22% (7/3 225), P=0.00]when 82.61%(38/46 cases) of patients with PLT<100×109/L. Post-splenectomy are risk factors for thrombosis in ITP patients, P values was 0.022, There was no statistical difference in the presence or absence of thrombotic events whether received glucocorticoid or TPO/TPO-Ra treatment, the P values were 0.075 and 0.531, respectively.@*Conclusions@#In Chinese population, ITP disease maybe with a higher risk of thrombosis, there was no positive correlation between thrombosis and platelet level; and had obvious age distribution characteristics. The history of tobacco, hypertension, diabetes and post-splenectomy are risk factors for thrombosis in ITP patients.

Clinical evaluation of Chinese disseminated intravascular coagulation scoring system (version 2017) in patients with acute promyelocytic leukemia / 中华血液学杂志

Objective@#To evaluate the applicability of Chinese disseminated intravascular coagulation scoring system (CDSS) in the diagnose of DIC in patients with acute promyelocytic leukemia (APL) patients. @*Methods@#Medical records of 220 APL patients diagnosed and receiving induction therapy in Blood Disease Hospital, CAMS & PUMC from January 2004 to February 2018 were retrospectively analyzed. Each patient was evaluated by CDSS, the International Society of Thrombosis and Haemostais (ISTH) scoring system for overt DIC and Japanese Ministry of Health and Welfare (JMHW) scoring system for overt DIC, respectively. @*Results@#A total of 220 APL patients were enrolled in the study, with a median age of 38.5 (12-70) years, 114 male and 106 female. Among them, 173 were in the low-medium risk group, 47 high-risk group; 11 patients died during induction treatment. The positive rates of DIC diagnosed by CDSS criteria, ISHT criteria, JMHW criteria was 62.27%, 54.09%, 69.09%, respectively. The consistency rate of CDSS and ISTH in diagnosing DIC was 78.10%; the consistency rate of CDSS and JMHW was 88.32%. There was significant difference in PT, APTT, FIB, D-Dimer and FDP in DIC(+) and DIC(-) group by CDSS (all P<0.05), but patients in the DIC(+) group had lower level of D-Dimer than in the DIC(-) group [21.9(1.2-477.1) mg/L vs 26.3(0.6-488.7) mg/L, χ2=1.871, P=0.002] by ISTH, and there was not significant difference in APTT by JMHW [27.05(18.0-181.0) s vs 26.15(18.2-35.5) s, χ2=1.162, P=0.134]. In this study, both of the gender and age had no difference in the DIC (+) and DIC (-) group by CDSS. Univariate analysis showed that the level of WBC and the percent of abnormal promyelocytic cells in bone marrow when diagnosed were different in DIC (+) and DIC (-) group by CDSS (P<0.05). Multiple analysis showed the level of WBC (OR=3.525, 95% CI 1.875-6.629, P<0.001) was the only independent predictor in DIC diagnosis by CDSS. @*Conclusion@#The sensitivity of diagnosing DIC by CDSS was higher than the ISTH; and the specificity was superior to JMHW. Using CDSS can help to make the DIC diagnosis and treatment in time for APL patients who with the coagulation abnormalities.

The efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia / 中华血液学杂志

Objective@#To investigate the safety and efficacy of eltrombopag for adult patients with chronic immune thrombocytopenia (cITP).@*Methods@#It was a randomised, single-centre, 6 weeks, placebo-controlled study. Beginning in January 29th, 2013, 35 patients were enrolled, and the trial was completed on May 16th, 2014. 17 patients were assigned to receive eltrombopag (starting dose 25 mg/d) and 18 were assigned to receive placebo.@*Results@#A total of 35 cases of adult cITP, 6 males and 29 females with a median age of 42(22-66) years were enrolled. One patient withdrew from eltrombopag treatment group for the adverse event (AE) and discontinued treatment. In first two weeks, 27.78% (5/18) of placebo-treated compared with 64.71%(11/17) of eltrombopag-treated patients achieved platelet counts ≥ 30×109/L(P=0.031); Treatment 6 weeks, the proportion of platelet counts reached ≥50×109/L and ≥ 30×109/L in eltrombopag-treated were higher than placebo-treated ones with statistically significant differences in both groups [64.71%(11/17) vs 11.11% (2/18), P=0.001; 76.47% (13/17) vs 38.89% (7/18), P=0.028]; The study also indicated a statistically significant difference in favour of eltrombopag compared with placebo in the odds of achieving the outcome of a platelet count ≥ 50×109/L at least once during 6-week treatment (94.11% vs 33.33%, P<0.001), and 70.59%(12/17) of patients with the platelet count continuously ≥ 50×109/L in 50% of treatment time in eltrombopag-treated group was more than placebo-treated one [11.11%(2/18), P<0.001]. Proportions of patients who required rescue treatment were 44.44% in placebo group and none in eltrombopag-treated one, respectively (P=0.002); The odds of bleeding symptoms with the WHO bleeding scale had no difference in both groups after 6 weeks (P=0.066). Adverse events that occurred more frequently due to eltrombopag than placebo included increased transaminase (3/17) and blood bilirubin (5/17), cerebral infarction(1/17).@*Conclusions@#The thrombopoietin receptor agonist eltrombopag was a suitable therapeutic option for Chinese adults with cITP.

Immune tolerance induction in a case of hemophilia B with inhibitor with prothrombin complex concentrate and rituximab / 中华血液学杂志

Objective@#To explore the immune tolerance induction (ITI) in a case of severe hemophilia B patient with inhibitor.@*Methods@#The F Ⅸ∶C was detected using a one-stage method and FIX inhibitor was assayed using Bethesda method. ITI was performed with prothrombin complex concentrates (PCC) in combination with rituximab.@*Results@#His past exposure days (ED) with PCC were 20 ED and his peak FⅨ inhibitor titer was 56 BU/ml. When his FIX inhibitor titer decreased to 10.4 BU/ml in Nov. 2015 and after receiving the informed consent from his parents, ITI was started. PCC with low dose rituximab successfully eradicated the high titer inhibitor within 17 months. There was no anaphylaxis, thrombotic event and infection.@*Conclusion@#This is the first case report for successful immune tolerance induction therapy in Chinese hemophilia B patient. ITI using PCC combined with rituximab is an effective choice to induce immune tolerance of hemophilia B with inhibitor.

Analysis of clinical efficacy of recombinant activated factor Ⅶ on bleeding in patients with hematologic disorders / 中华血液学杂志

Objective@#To investigate the treatment efficacy of recombinant activated factor Ⅶ (rFⅦa) for bleeding among patients with hematologic disorders.@*Methods@#A total of 38 times of bleeding in 31 patients with hematological disease treated with rFⅦa were analyzed retrospectively.@*Results@#The clinical effective rate of rFⅦa for bleeding management in acquired hemophilia A (AHA) patients/hemophilia patients with inhibitor, acute promyelocytic leukemia (APL) patients and patients with non-APL leukemia was 90% (9/10) , 71.4% (5/7) and 60.0% (3/5) , respectively, which was higher than that in patients following HSCT (30.8%) . The clinical effective rate of rFⅦa for patients with bleeding score of 2 (100.0%) was higher than that with 3 (66.7%) and 4 (54.1%) . The effective rate of rFⅦa was 25.0% (2/5) in 5 patients with cerebral hemorrhage, 66.7% (6/9) in 9 patients with hematuria and 41.7% in 12 patients with gastrointestinal hemorrhage. The curative effect for 3 patients with joints and muscle bleeding and 5 patients with skin, nasal, pharyngeal and gum bleeding was excellent. Following HSCT, among patients with bleeding score of 4 points, high dose and repeated use of rFⅦa did not necessarily achieve a good effect. Among AHA/hemophilia patients with inhibitors and patients with acute leukemia who had bleeding score of 4 points, the use of low dose FⅦa could achieve good therapeutic effect, however the efficacy of lowest dose (22.5 μg/kg) rFⅦa was poor.@*Conclusions@#The hemostasis efficacy of rFⅦa is affected by various factors such as diseases, bleeding sites, bleeding score and so on. The use of rFⅦa can achieve good efficacy for bleeding management in AHA patients/hemophilia patients with inhibitor, APL patients and patients with non-APL leukemia. However the efficacy of rFⅦa for bleeding of patients after HSCT is poor. Early use of rFⅦa is important for successful hemostatic treatment. Management of underlying condition is as important as hemostatic treatment.

Predictors of fatigue among individuals with primary immune thrombocytopenia in China / 中华血液学杂志

Objective@#To study the fatigue symptoms of adult patients with primary immune thrombocytopenia (ITP) and to analyze the possible factors that affect the severity of fatigue.@*Methods@#Eligible adult patients with ITP who admitted to Institute of Hematology & Blood Diseases Hospital were enrolled in this study and the questionnaires including a Chinese version of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) , the Pittsburgh sleep quality index (PSQI) , the Hospital Anxiety and Depression scale (HADS) and demographic information were completed. The predictors of fatigue were determined with multiple linear regression analyses.@*Results@#A total of 207 patients with ITP were enrolled, including 70 males (33.8%) and 137 females (66.2%) , the median age was 42 (18-72) years old. The FACIT-F score in ITP patients was (37.50±9.05) . The FACIT-F severity of ITP patients was positively correlated with the platelet count (r=0.307, P<0.001) . The FACIT-F severity was negatively correlated with bleeding severity (r=-0.276, P<0.001) , sleep quality (r=-0.654, P<0.001) , depression (r=-0.598, P<0.001) and anxiety (r=-0.616, P<0.001) . A multiple linear regression analysis revealed that the severity of ITP-related fatigue was significantly correlated with platelet count (P<0.001) , bleeding severity (P=0.004) , sleep quality (P<0.001) and depression (P<0.001) .@*Conclusion@#Fatigue was determined by complicated factors in adult ITP patients. Interventions addressing depressive symptoms, sleep quality, bleeding symptoms and platelet count could be potential avenues for treatment of fatigue in patients with ITP.

A prospective study of the efficacy and safety of maintenance therapy with recombinant human thrombopoietin in patients with primary immune thrombocytopenia: a multicenter study / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO.@*Methods@#Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×109/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×109/L.@*Results@#A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×109/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×109/L) at 4th week, 8th week and 12th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×109/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild.@*Conclusion@#Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

Clinical evaluation of the revised International Prognostic Score of Thrombosis for essential thrombocythemia (IPSET-thrombosis) in a cohort of 746 Chinese adult patients / 中华血液学杂志

Objective@#To evaluate the role of the revised International Prognostic Score of Thrombosis (IPSET-thrombosis) in predicting the occurrence of thrombotic events in Chinese patients with essential thrombocythemia (ET) and to develop a thrombosis predicting model more applicable to Chinese ET patients.@*Methods@#Medical records of 746 adult patients with an initial diagnosis of ET were retrospectively analyzed.@*Results@#The median age at diagnosis was 52 (18-87) years, with 305 males and 441 females. According to the revised IPSET-thrombosis model, the number of very low-, low-, intermediate-, and high-risk patients were 271 (36.3%) , 223 (29.9%) , 63 (8.4%) and 189 (25.3%) , respectively. The four groups exhibited significantly different thrombosis-free survival (χ2=72.301, P<0.001) . Thirty-six patients were reclassified as intermediate-risk according to the revised IPSET-thrombosis instead of low-risk as per the original IPSET-thrombosis. Nineteen intermediate-risk patients as per the original IPSET-thrombosis were upgraded to high-risk according to the revised IPSET-thrombosis. Fifty-one high-risk patients as per the original IPSET-thrombosis were reclassified as low-risk in the revised IPSET-thrombosis. It suggests that the revised IPSET-thrombosis potentially avoids over- or under-treatment. In low-risk patients as per the revised IPSET-thrombosis, the rate of thrombosis in patients with cardiovascular risk factors (CVF) was higher than that in those without (16.3% vs 5.2%, χ2=5.264, P=0.022) , and comparable with intermediate-risk patients as per the revised IPSET-thrombosis (16.3% vs 14.3%, χ2=0.089, P=0.765) . As a result, a new revised IPSET-thrombosis model more applicable to Chinese ET patients was developed in which patients with CVF in the low-risk group as per the revised IPSET-thrombosis were reclassified as intermediate-risk group.@*Conclusion@#For predicting the occurrence of thrombotic events, the revised IPSET-thrombosis model was better than the original IPSET-thrombosis model. The revised IPSET-thrombosis was optimized and a new revised IPSET-thrombosis model more applicable to Chinese ET patients was developed, and the new evidence for risk stratification and treatment of ET in Chinese was provided.

Lupus anticoagulant: two cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To deepen the understanding of clinical manifestations and treatment of patients with positive lupus anticoagulant (LAC).</p><p><b>METHODS</b>The clinical data of 2 patients were analyzed and related literature were reviewed.</p><p><b>RESULTS</b>Case 1, a 31-year-old female, diagnosed as lupus anticoagulant positive, secondary to undifferentiated connective tissue disease, was presented with menorrhagia and thrombocytopenia. Anti-nuclear antibody (ANA) was positive 1:1000 (homogeneous type) with anti-double stranded DNA positive, and dRVVT LA1/LA2 was 3.4. Coagulation function was alleviated after treatment with glucocorticoid and total glucosides of paeony. Case 2, a 59-year-old female was presented with gingival bleeding, hematuria with the level of F II:C 13%. dRVVT LA1/LA2 was 2.0. Anti-nuclear antibody (ANA) was positive 1:1000 (type of cytoplasmic granule), anti-double stranded DNA was positive. The patient was diagnosed as hypoprothrombinemia-lupus anticoagulant syndrome (LAHS) and acquired coagulation factor deficiency. The signs of hemorrhage were alleviated after treatment with methylprednisolone 40 mg/day and cyclophosphamide, while the level of F II:C was below normal.</p><p><b>CONCLUSION</b>Symptoms of patients with positive LAC are variable. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. Cases of LAHS should be thoroughly investigated for any known causes and related disorder.</p>

Clinical analysis of recombinant human thrombopoietin for 92 adults with severe primary immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of recombinant human thrombopoietin (rhTPO) and related factors which influencing the therapeutic effect in adults with severe immune thrombocytopenia (ITP).</p><p><b>METHODS</b>The efficacy of rhTPO in 92 hospitalized adult patients [35 males and 57 females, median age as 34 (18-65) years] with severe ITP, including 7 cases of newly diagnosed ITP, 29 cases of persistent ITP and 56 cases of chronic ITP from May 2012 to May 2014 was retrospectively investigated. All patients received subcutaneous rhTPO, the injected dosage was 300 U·kg⁻¹·d⁻¹ for 14 days, platelet counts were recorded and followed-up for a week.</p><p><b>RESULTS</b>The overall response rate of rhTPO treatment was 60.9%. The overall response rates in newly diagnosed, persistent and chronic ITP were 71.4%, 62.1% and 58.9% respectively. The median platelet counts on fourth，seventh, fourteenth days of treatment, and the seventh day of withdrawal were 27(5-49), 65(16-138), 133(28-208) and 67(15-134)×10⁹/L, respectively. The median time was 6(5-7) days when platelet counts reached 100×10⁹/L, the median peak time was 11(5-17) days, the median maximum peak of platelet counts was 194(132-274)×10⁹/L in patients who reached CR after treatment. Related factors which affected therapeutic effect were analyzed in patients who reached CR after treatment, and indicated that sex, age, disease stage, express of platelet membrane glycoprotein (GP) and relative number of CD19+ B, CD3+CD4+ T, CD3+CD8+ T lymphocyte in blood samples did not influence the probability of complete response (P>0.05). A few patients with fever, muscle aches, fatigue or dizziness could be self-recovery without special intervention.</p><p><b>CONCLUSION</b>Severe ITP in adults treated by rhTPO had satisfactory therapeutic effect and safety.</p>

Efficacy and safety of rhTPO in the treatment of pediatric primary immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment of pediatric primary immune thrombocytopenia (ITP).</p><p><b>METHODS</b>The clinical characteristics of 41 pediatric ITP patients who received rhTPO therapy from December 2006 to September 2014 were retrospectively analyzed (as rhTPO group). During the same time another 26 pediatric ITP patients who received vindesine combined with human immunoglobulin therapy were selected as control group. The treatment outcomes were evaluated.</p><p><b>RESULTS</b>A total of 67 cases of pediatric ITP, 31 males and 36 females with a median age 10.0(1.6-17.0) years were enrolled, including 19 cases of newly disgnosed ITP, 18 cases of persistent ITP and 30 cases of chronic ITP. Of them, 43 cases of whom were severe ITP (PLT<10×10⁹/L). The total response rate had no statistically significant difference between the rhTPO group and the control group (68.29% vs 65.38%, P=0.806), neither in newly ITP, persistent and chronic ITP (P=0.320, P=0.763). In severe ITP patients, 17 of 30 cases (56.67%) achieved response with rhTPO therapy, while the control group was 61.54% (8/13) (P=0.766). The median maximum peak of platelet counts and the time of the platelet counts >30×10⁹/L and > 50×10⁹/L had no statistically significant differences in rhTPO group compared with the control group [52(7-608)×10⁹/L vs 40(3-152)×10⁹/L, P=0.05; 7(3-13) d vs 4(2-24) d, P=0.202; 7.5(4-15) d vs 5.5(4-23) d, P=0.557]. The mean platelet counts were 43(3-605)×10⁹/L in the rhTPO group, which were higher than the control group [32(-14-149)×10⁹/L, P=0.042]. No severe adverse effects were observed in both groups.</p><p><b>CONCLUSION</b>For pediatric ITP, rhTPO has a similar outcomes with vindesine combined with human immunoglobulin, and it is an effective and safe treatment option.</p>

Application of immature platelet fraction absolute immature platelet fraction and thrombelastograph on assessment of bleeding risk in patients with immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical value of immature platelet fraction (IPF), absolute immature platelet fraction (A- IPF) and thrombelastograph (TEG) on assessment of bleeding risk of immune thrombocytopenia (ITP).</p><p><b>METHODS</b>two hundred and seventy- one patients with ITP were assessed based on ITP-BAT bleeding grading system. IPF, A-IPF were determined in 271 patients ,TEG in 125 patients. The correlations between bleeding grades and IPF, A-IPF, variables of TEG in subgroups were analyzed by statistical method. The predictive value of IPF, A-IPF, and variables of TEG on bleeding risk of ITP patients was evaluated.</p><p><b>RESULTS</b>There were no significant differences in bleeding degree in all patients with different gender and disease stage (P>0.05). Mild bleeding rate in children was higher than that in adult (P<0.05). PLT inversely correlated with bleeding grade for the entire cohort (P<0.001). In all subjects, PLT< 30 × 10⁹/L and pediatric cohorts with PLT< 30 × 10⁹/L, PLT were negatively correlated with IPF (P<0.05), positive correlated with A-IPF (P<0.001) and the maximum amplitude (MA (P<0.05). Bleeding grades were significantly correlated with IPF, A-IPF, MA in all subjects and patients with PLT< 30 × 10⁹/L (P<0.001). IPF, A-IPF and MA did not correlate with bleeding grades in children with PLT< 30 × 10⁹/L (P>0.05). ROC curve analysis revealed IPF, A-IPF and MA had better predictive value (AUC 0.745, 0.744, 0.813, P<0.001). Multivariate analysis showed that IPF and MA were independence factors for predicting bleeding risk in ITP patients and comprehensive predictive value was higher (AUC 0.846, P<0.001) than single variable.</p><p><b>CONCLUSION</b>IPF, A-IPF and MA could accurately evaluate bleeding risk in ITP patients. It may be considered as reference index of the treatment and observation index of curative effect.</p>

Clinical analysis of lower doses rituximab for children primary immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of lower doses rituximab(375 mg/m²×1) in primary children immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Fifty children [23 male and 27 female, the median age was 9.5 years (rage 3.5-17.0 years)]with persistent and chronic ITP were treated with lower doses rituximab from January 2009 to January 2013 in our hospital. Efficacy and side effects of lower doses rituximab was studied, and factors related to the outcomes were analyzed.</p><p><b>RESULTS</b>Among fifty patients, 17/50(34%) achieved a complete response (CR) and 15/50 (30%) patients got response (R). Patients with CR continued to maintain a platelet count above 50×10⁹/L at a median 12.3 (6-40) months. Patents with R continued to maintain a platelet count above 30×10⁹/L at a median 6 (2-12) months. The overall response (OR) in 3 and 6 months were 58% (29/50), 64% (32/50) respectively. Six patients have mild and transient side effects, including urticarial rash and fever, which were promptly resolved with appropriate therapy. Sex, age at diagnosis, interval from diagnosis to initial treatment with rituximab, platelet count at treatment and CD19+B cell count did not influence the overall response and complete response (P>0.05). Patients with anti-GPIIb/IIIa autoantibody had a better OR (P<0.05).</p><p><b>CONCLUSION</b>Children with persistent and chronic ITP treated by lower doses rituximab had better therapeutic effects. Patients with anti-GPIIb/IIIa autoantibody had better response. Rituximab was well tolerated and no related serious side effects were recorded in the study.</p>

Clinical characteristics and risk factors for major thrombosis in 604 Chinese patients with low-risk essential thrombocythemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze clinical and molecular characteristics of low-risk essential thrombocythemia (ET) in a large cohort of Chinese patients and to explore risk factors for major thrombosis and treatment strategies.</p><p><b>METHODS</b>Medical records of patients with an initial diagnosis of ET from March 1982 to May 2012 in our hospital were retrospectively analyzed.</p><p><b>RESULTS</b>A total of 604 low-risk ET patients were enrolled with a median follow-up of 49 months (range:0-338). 43(7.1%) patients experienced major thrombotic events. Cox proportional hazards regression revealed JAK2 V617F mutation (HR=2.279; P=0.035) and cardiovascular risk factors (CVF) (HR=2.541; P=0.006) to be risk factors for total thrombotic events, while only CVF (HR=2.633; P=0.008) was risk factor for arterial thrombosis. None of the evaluated factors was related to venous thrombosis. Patients with both JAK2 V617F mutation and CVF had a worse thrombosis- free survival than those with only one risk factor (P<0.05). In patients with JAK2 V617F or CVF alone, antiplatelet treatment (P=0.016) significantly decreased the risk of thrombosis, while those with both JAK2 V617F and CVF could benefit from cytoreductive agents (P=0.018).</p><p><b>CONCLUSION</b>Chinese low-risk ET patients have a lower risk of thrombosis than Caucasian low-risk ET patients. JAK2 V617F mutation and CVF are the most significant risk factors for thrombosis. Existence of both risk factors further increases the thrombotic risk. Treatment strategies on low-risk ET patients should be made based on presence or absence of risk factors.</p>

Clinical significance of ITP-BAT bleeding grading system for patients with immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance, reliability and responsiveness of ITPBAT bleeding grading system for patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>One hundred and eighty-three patients with ITP were assessed by using of ITP-BAT bleeding grading system. Test-retest reliability, responsiveness of ITP-BAT bleeding grading system and association between bleeding grades and platelet counts, age, gender, disease stage were analyzed.</p><p><b>RESULTS</b>Bleeding degree of ITP patients and the platelet count were negatively correlated (r=- 0.744, P<0.01) and bleeding degree increased significantly with platelet counts below 20×10⁹/L (χ²=82.40，P<0.01). Mild bleeding rate in children was 68.5%, higher than that in adult(χ²=8.839，P<0.01), and severe bleeding rate in the elderly was 14.3%, higher than that in non-elderly(χ²=7.056，P<0.01). There were no significant differences in bleeding degree in patients with different gender and disease stage (χ²=4.922, P>0.05 and χ²=3.411, P>0.05). Bleeding grades before and after treatment had more significant difference(Z=-6.61, P<0.01). Scoring consistency of two doctors was 66.1% (κ=0.561), and scoring consistency of the same doctor was 94.7% (κ=0.874).</p><p><b>CONCLUSION</b>ITP-BAT bleeding grading system in China has good validity and responsiveness, closely related to clinical indicators. It is sensitive to the variation of the hemorrhage in patients. ITP-BAT could be used as a reference index of the treatment, and also be used as an observation index of curative effect.</p>

Chronic disseminated intravascular coagulopathy associated with aortic dissecting aneurysms: two cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To report two cases of chronic disseminated intravascular coagulation associated (DIC) with aortic dissecting aneurysm, and discuss the treatment strategy.</p><p><b>METHODS</b>The clinical data of two patients with chronic DIC associated with aortic dissecting aneurysm were analyzed and the related literature was reviewed.</p><p><b>RESULTS</b>Case 1: female, 53 years old, she had gingival bleeding, skin ecchymosis and haematuria for 2 months, the laboratory test revealed PLT 48 × 10⁹/L, APTT 38.0 s and fibrinogen 0.53 g/L; Case 2: male 86 years old, he had skin petechia and ecchymosis,gingival bleeding for 2 weeks, the laboratory test revealed PLT 17×10⁹/L, APTT 37.5 s and fibrinogen 0.51 g/L. CT scan for both cases revealed aortic aneurysm. They were diagnosed as aortic aneurysm associated chronic DIC. Both of them received blood component transfusion. After the treatment, they showed improvement in bleeding symptoms and laboratory data. They gave up operation, and were discharged from the hospital at last.</p><p><b>CONCLUSION</b>Blood replacement can alleviate bleeding tendency in those patients with chronic DIC associated with aortic dissecting aneurysm.</p>

Survivin-siRNA inhibits proliferation of lung cancer A549 cells and enhances their chemosensitity to cisplatin / 中国肿瘤生物治疗杂志

Objective:To investigate the effect of survivin-siRNA plasmid on survivin expression in human lung cancer cell line A549, and to observe its effect on the apoptosis, proliferation, and chemosensitivity of A549 cells. Methods: pSilencer-survivin-siRNA (survivin-siRNA) plasmid was constructed using pSilencer-U6 plasmid and was transfected into A549 cells. Expression of survivin mRNA and protein was examined by RT-PCR and Western blotting analysis, respec-tively. Apoptosis and proliferation of A549 cells were examined by DAPI staining and MTT, respectively. Results: Sur-vivin-siRNA plasmid was successfully constructed, and it significantly inhibited survivin mRNA and protein expression in A549 cells. Survivin-siRNA transfection induced apoptosis, inhibited proliferation and increased chemosensitivity of A549 cells to cisplatin. Conclusion: pSilencer-survivin-siRNA can silence survivin expression in A549 cells and subsequently inhibit proliferation, promote apoptosis, and enhance chemosensitivity of A549 cells to cisplatin. Survivin may serve as a potential target for gene therapy of lung cancer.