Yang R

[Chronic disseminated intravascular coagulopathy associated with aortic dissecting aneurysms: two cases report and literature review].

OBJECTIVE To report two cases of chronic disseminated intravascular coagulation associated (DIC) with aortic dissecting aneurysm, and discuss the treatment strategy. METHODS The clinical data of two patients with chronic DIC associated with aortic dissecting aneurysm were analyzed and the related literature was reviewed. RESULTS 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. CONCLUSION Blood replacement can alleviate bleeding tendency in those patients with chronic DIC associated with aortic dissecting aneurysm.

[Clinical characteristics and risk factors for major thrombosis in 604 Chinese patients with low-risk essential thrombocythemia].

OBJECTIVE 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. METHODS Medical records of patients with an initial diagnosis of ET from March 1982 to May 2012 in our hospital were retrospectively analyzed. RESULTS 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). CONCLUSION 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.

Clinical analysis of recombinant human thrombopoietin for 92 adults with severe primary immune thrombocytopenia

目的 评价重组人血小板生成素（rhTPO）治疗成人重型原发免疫性血小板减少症（ITP)的疗效及安全性。 方法 对2012年5月至2014年5月期间收治的92例成人重型ITP患者的临床资料进行回顾性分析。其中新诊断ITP 7例、持续性ITP 29例、慢性ITP 56例，男35例、女57例，中位年龄34 (18~65）岁。全部患者接受rhTPO 300 U·kg−1·d−1×14 d治疗，停药后观察7 d。 结果 全部92例患者rhTPO治疗的总反应率为60.9%(56/92)，新诊断ITP、持续性ITP、慢性ITP患者总反应率分别为71.4%、62.1%、58.9%。所有患者治疗第4、7、14天与停药第7天中位PLT分别为27(5~49)、65(16~138)、133 (28~208)、67(15~134)×109/L。获完全反应的患者PLT达到100×109/L的中位时间为6(5~7)d, PLT达峰值中位时间为11(5~17)d，中位PLT峰值为194(132~274)×109/L。患者性别、年龄、疾病分期、血小板膜糖蛋白特异性抗体表达及外周血CD19+B、CD3+CD4+T、CD3+CD8+T淋巴细胞数量均与疗效无相关性(P>0.05)。少数患者出现低热、肌肉酸痛、乏力、头晕，均自行恢复。 结论 rhTPO治疗成人重型ITP具有较好的疗效和安全性。OBJECTIVE To evaluate the efficacy of recombinant human thrombopoietin (rhTPO) and related factors which influencing the therapeutic effect in adults with severe immune thrombocytopenia (ITP). METHODS 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. RESULTS 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. CONCLUSION Severe ITP in adults treated by rhTPO had satisfactory therapeutic effect and safety.

Prediction of infections within 6 months of the initial diagnosis in adults with immune thrombocytopenia by absolute lymphocyte count

目的 研究成人原发免疫性血小板减少症（ITP）患者诊断后6个月内感染的发生率、危险因素及预后情况，评估初诊淋巴细胞绝对值（ALC）对感染的预测价值。 方法 回顾性分析217例初诊成人ITP患者的临床资料，分析6个月内合并感染的危险因素，评估初诊ALC在ITP患者诊断后6个月内合并感染的预测价值以及与预后的相关性。 结果 217例成人ITP患者诊断后6个月内的感染发生率为13.8%（30/217），≥60岁患者感染发生率为25.0%（14/56）。多因素分析发现性别、ALC是发生感染的独立危险因素（P<0.05，95%CI 1.150~7.298，OR 2.722；P<0.01，95%CI 6.802~80.749，OR 23.436）。ALC预测感染的分界值是1.225×109/L（敏感性0.866，特异性0.700）。ALC≤1.225×109/L组与ALC>1.225×109/L组比较，感染发生率较高（45.7%对5.3%，χ2=49.151，P<0.01），持续缓解率和1年生存率差异无统计学意义（28.0%对26.0%，χ2=0.071，P>0.05；98.6%对97.8%，χ2=0.095，P>0.05）。6个月内发生感染与无感染患者比较，1年生存率较低（93.3%对99.3%，χ2=4.607，P<0.05），持续缓解率差异无统计学意义（30.0%对27.3%，χ2=0.096，P>0.05）。 结论 初诊ALC可以作为ITP患者诊断后6个月内合并感染风险的预测指标。感染是影响ITP患者预后的主要因素。OBJECTIVE To explore incidence, risk factors and prognosis of the first 6 months infectious events in adults with newly diagnosed primary immune thrombocytopenia (ITP), and evaluate the value of initial absolute lymphocyte count (ALC) in predicting infection. METHODS The initial clinical records and infectious events during 6 months of 217 adult with newly diagnosed ITP were retrospectively analyzed. Statistical methods were used to analyze risk factors of the 6 months infections in adults ITP, the prediction of ALC in risk of infection, and the association of ALC and prognosis. RESULTS Infection rate of ITP patients accepting therapy within 6 months after the initial diagnosis was 13.8% (30/217), and infection rate of patients ≥ 60 years of age 25% (14/56). Multivariate unconditioned Logistic analysis showed that gender and ALC were independent risk factors for the 6 months infection of ITP patients (P<0.05, 95% CI 1.150-7.298, OR 2.722 and P<0.001, 95% CI 6.802-80.749, OR 23.436). Cutoff value of ALC was 1.225 × 10⁹/L, sensitivity and specificity of its value were 0.866 and 0.700 respectively. Infection rate of ALC>1.225 × 10⁹/L in adult ITP was lower than of ALC ≤ 1.225 × 10⁹/L (5.3% vs 45.7%, χ² = 49.151, P<0.001). Furthermore, persistent recovery and the 1-year mortality rate after diagnosis had no difference among patients of different ALC (28.0% vs 26.0%, χ² = 0.071, P>0.05, and 98.6% vs 97.8%, χ² = 0.095, P>0.05). There were no significant differences in persistent recovery in patients with and without infection (30.0% vs 27.3%, χ² = 0.096, P>0.05). The 1-year mortality rate after diagnosis was significantly lower in those patients who developed an infection (93.3% vs 99.3%, χ² = 4.607, P<0.05). CONCLUSION Initial ALC was an independent risk factor of 6 months infection in adult ITP. It could be a predictive index of infection within 6 months of the initial diagnosis in ITP patients. Infection as an important factor affected the survival of ITP patients.

Application of immature platelet fraction absolute immature platelet fraction and thrombelastograph on assessment of bleeding risk in patients with immune thrombocytopenia

OBJECTIVE 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). METHODS 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. RESULTS 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. CONCLUSION 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.目的 探讨未成熟血小板比例（IPF）、未成熟血小板绝对值（A-IPF）和血栓弹力图（TEG）在原发免疫性血小板减少症（ITP）患者出血倾向评估中的价值。 方法 采用ITP-BAT出血评分系统对271例ITP患者进行出血评分及出血程度分级，并行IPF、A-IPF检测，其中125例行TEG检测，分析ITP患者出血程度与IPF、A-IPF、TEG各指标的相关性。 结果 在271例ITP患者中，不同疾病分期和性别患者的出血程度差异无统计学意义（P>0.05）；儿童以轻度出血为主，与成人出血程度差异有统计学意义（P<0.05）；出血程度和血小板计数呈负相关（P<0.001）。在所有患者、PLT<30×109/L患者以及PLT<30×109/L儿童患者中，血小板计数与IPF呈负相关（P<0.05），与A-IPF、血栓最大幅度（MA）值呈正相关（P<0.05）。在所有患者及PLT<30×109/L患者中，出血程度和IPF呈正相关（P<0.001），与A-IPF、MA值呈负相关（P<0.001）。在PLT<30×109/L儿童患者中，出血程度与IPF、A-IPF、MA值均无相关性（P>0.05）。ROC曲线分析显示IPF、A-IPF、MA值评估ITP患者出血风险效能较好，ROC曲线下面积分别为0.745、0.744、0.813（P<0.001）。多因素分析显示IPF和MA值是预测ITP患者出血倾向的独立因素，综合诊断ROC曲线下面积0.846（P<0.001），优于单一指标。 结论 IPF、A-IPF和MA值能够准确评估ITP患者的出血风险，可以作为治疗的参考指标和疗效的观察指标。

Efficacy and safety of rhTPO in the treatment of pediatric primary immune thrombocytopenia

OBJECTIVE To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment of pediatric primary immune thrombocytopenia (ITP). METHODS 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. RESULTS 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. CONCLUSION For pediatric ITP, rhTPO has a similar outcomes with vindesine combined with human immunoglobulin, and it is an effective and safe treatment option.目的 观察重组人血小板生成素（rhTPO）治疗儿童原发免疫性血小板减少症（ITP）的疗效及安全性。 方法 回顾性分析2006年12月至2014年9月接受rhTPO治疗（rhTPO组）的41例儿童ITP患者临床资料，与同期接受长春地辛联合静脉丙种球蛋白治疗（对照组）的26例ITP患儿进行对比观察。 结果 全部67例ITP患儿中男31例、女36例，中位年龄10.0(1.6~17.0）岁；新诊断ITP 19例，持续性ITP 18例，慢性ITP 30例；重症ITP(PLT<10×109/L) 43例。rhTPO组与对照组总有效率差异无统计学意义[68.29%（28/41）对65.38%（17/26），P=0.806]。rhTPO组与对照组新诊断ITP、持续性及慢性ITP患儿总有效率差异均无统计学意义（P值分别为0.320和0.763）。rhTPO组与对照组重症ITP患儿总有效率差异无统计学意义[56.67%（17/30）对61.54%（8/13），P=0.766]。rhTPO组与对照组治疗后PLT峰值、PLT>30×109/L时间、PLT>50×109/L时间差异均无统计学意义[52(7~608）×109/L对40(3~152）×109/L，P=0.05; 7(3~13) d对4(2~24) d，P=0.202; 7.5(4~15) d对5.5(4~23) d，P=0.557]。rhTPO组治疗后PLT升高值于对照组[43(3~605）×109/L对32（−14~149）×109/L，P=0.042]。两组患儿均无明显不良反应发生。 结论 rhTPO单药治疗儿童ITP的疗效与长春地辛联合静脉丙种球蛋白相当，安全性较好。

[Clinical significance of ITP-BAT bleeding grading system for patients with immune thrombocytopenia].

OBJECTIVE To explore the clinical significance, reliability and responsiveness of ITPBAT bleeding grading system for patients with immune thrombocytopenia (ITP). METHODS 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. RESULTS 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). CONCLUSION 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.

Clinical analysis of lower doses rituximab for children primary immune thrombocytopenia

OBJECTIVE To evaluate the efficacy and safety of lower doses rituximab(375 mg/m²×1) in primary children immune thrombocytopenia (ITP). METHODS 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. RESULTS 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). CONCLUSION 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.

[Acquired coagulation factor X deficiency: three cases report and literature review].

OBJECTIVE To deepen the understanding of acquired coagulation factor X (F X) deficiency. METHODS The clinical data of 3 patients were analyzed and related literature were reviewed. RESULTS Case 1, a 57-year-old male, secondary to multiple myeloma and amyloidosis, was presented with spontaneous mucous hemorrhage with the level of FX:C 1.8%, which kept unchanged after chemotherapy with melphalan, glucocorticoid, and thalidomide, and died of primary disease progression. Case 2, a 41-year-old male with psoriasis, was presented with cerebral and retinal hemorrhage with the level of FX:C 26.8%. The signs of hemorrhage were alleviated after the supplement of folic acid, vitamin B12, and vitamin K, and transfusion with red blood cells, platelets, and fresh frozen plasma. Case 3, a 63-year-old female, associated with high level of lupus anticoagulant, was presented with repeated ecchymosis and haemarthrosis with the level of FX:C 6.1%, which was refractory to prothrombin complex concentrate, methyprednisolone, azathioprine, and rituximab. CONCLUSION Acquired FX deficiency is a rare disorder with variable symptoms. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. The prognosis of acquired FX deficiency is mainly related to the underlying disease.

Relationship between the expression of autoantibodies against platelet membrane glycoprotein and therapeutic effect in primary immune thrombocytopenia

OBJECTIVE To study the expression of specific anti- platelet glycoprotein autoantibodies GP II b/III a, GP I b/IX and GP I a/II a in primary immune thrombocytopenia (ITP), and to evaluate the relationship between the therapeutic effect and the expression of specific anti- platelet glycoprotein antibodies GPIIb/IIIa, GPIb/IX and GPIa/IIa. METHODS Anti-GPIIb/IIIa, GPIb/ IX and GP I a/II a antibodies were assayed by ELISA for patients with ITP. Total 442 patients in our hospital, who were retrospectively investigated from December 2010 to November 2012, were divided into newly diagnosed ITP, persistent and chronic ITP. The expression of specific anti- platelet glycoprotein antibody in each group was measured separately. The newly diagnosed ITP patients were treated with intravenous IgG (IVIG) and corticosteroids. The relationship between the expression of specific anti- platelet glycoprotein antibodies GPIIb/IIIa, GPIb/IX and GPIa/IIa and the complete response (CR) was studied. RESULTS Positive rates of anti- platelet glycoprotein antibodies were 59.09%, 26.97% and 37.35% respectively in newly diagnosed ITP, persistent and chronic ITP, the difference was statistical significant (P<0.05). In newly diagnosed ITP, positive rate of antibody against GPIIb/IIIa was 38.64%, double positive rate of antibodies against both GP II b/III a and GP I a/II a was 15.91%, there was statistical significance (P<0.05) compared with that of persistent and chronic ITP. The complete response (CR) rate in newly diagnosed ITP patients with positive antibody against GP II b/III a was 80.39% after treatment with IVIG and corticosteroids. There was statistical significance compared with that in patients having no antibodies (P<0.05). CONCLUSION The expression of antibodies against GP II b/III a and double positive for both GP II b/III a and GP I a/II a autoantibodies increased in newly diagnosed ITP patients. Patients with anti-GP II b/III a autoantibody had good response to medication with IVIG and corticosteroids.