Relative analysis of platelet activation with bleeding risk in patients with primary immune thrombocytopenia / 中华血液学杂志

Objective@#To study the relationship between platelet activation and the degree of bleeding in patients with primary immune thrombocytopenia (ITP) .@*Methods@#43 patients with ITP were assessed based on ITP-BAT bleeding grading system. Platelet membrane glycoproteins (GP) Ⅰb, GPⅡb/Ⅲa and P-selectin expression were detected by flow cytometry analysis with and without adenosine diphosphate (ADP) stimulation. Association of platelet activation with platelet count, immature platelet fraction (IPF) , bleeding severity were evaluated.@*Results@#GPⅡb/Ⅲa and P-selection expressions on unstimulated platelet in ITP patients were higher than those in healthy controls (65.69±10.73 vs 7.16±0.99, t=4.130, P<0.001; 15.43±1.41 vs 12.55±1.03, t=2.070, P=0.043, respectively) , and GPⅠb expression was lower than that in healthy controls (240.11±24.93 vs 295.11±22.15, t=2.417, P=0.020) . Comparatively to healthy individuals, following ADP stimulation, GPⅡb/Ⅲa expression in ITP patients increased (133.96±12.17 vs 39.67±4.99, t=5.256, P<0.001) , whereas GPⅠb and P-selection expressions decreased (37.09±3.94 vs 109.77±23.66, t=3.901, P<0.001; 149.06±19.14 vs 205.73±21.00, t=2.070, P=0.043, respectively) . ADP-stimulated GPⅠb, ADP-stimulated and unstimulated P-selection, proportion of GPⅠb, P-selection levels with/without ADP stimulation were significantly associated with platelet counts (P<0.05) . ADP-stimulated P-selection and proportion of P-selection levels with/without ADP stimulation were significantly associated with IPF (P<0.05) . There were significant differences in the expressions of unstimulated P-selection, ADP-stimulated P-selection, ADP-stimulated GPⅠb stratified by bleeding grades (P<0.05) . The ratios of P-selection, GPⅡb/Ⅲa and GPⅠb with/without ADP stimulation in ITP patients were significantly different among various bleeding grades (P<0.05) . Higher proportion of GPⅠb with/without ADP stimulation was associated with higher risk of bleeding (OR=3.05, P=0.011) . Lower proportion of GPⅡb/Ⅲa and P-selection with/without ADP was associated with higher risk of bleeding (OR=0.32, P=0.023; OR=0.04, P=0.006, respectively) .@*Conclusion@#Platelet activation index could accurately assess the degree of bleeding in patients with ITP, and also be used as the observation index and reference index for treatment.

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>

Relationship between initial absolute lymphocyte counts and the prognosis of children with primary immune thrombocytopenia / 中华实用儿科临床杂志

Objective To investigate the value of initial absolute lymphocyte counts (ALC) in predicting the prognosis of children with primary immune thrombocytopenia(ITP).Methods The initial clinical data of 214 children with incipient ITP were retrospectively analyzed and followed up for more than one year.Statistical analysis was made to find out the influence factors for the prognosis of patients with ITP in children to evaluate the predictive value of ALC on assessing the prognosis of ITP in children,and to analyze the association between ALC and outcomes and the clinical value of prognostic stratification.Results The remission rate of children with ITP was 71.5％ in 12 months.Multivariate unconditioned Logistic analysis showed that disease duration,the infection history,response to treatment and ALC were independent risk factors for chronic ITP(all P ＜ 0.05).Cutoff value of initial ALC was 3.005 × 109/L,sensitivity and specificity of value were 71.9％,83.6％.Three months and 12 months no remission rate of ITP in children between ALC ＞ 3.005 × 109/L and ≤ 3.005 × 109/L had statistical significant difference (24.2％ vs 64.9％,8.3％ vs 54.2％,x2 =42.13,P ＜0.001).There was no statistical difference in therapy efficacy between 2 groups(x2 =5.098,P ＞ 0.05).Remission rate between the ≤5 years old group and ＞ 5 years old group was statistical difference based on age stratification(x2 =22.371,22.177,all P ＜ 0.01).ITP in children were stratified into low risk group,intermediate risk group,high risk group based on the initial ALC and infection history,with remission rates in 3 month respectively 75.8％,54.1％,22.8％,respectively,and 91.6％,68.4％,31.6％ in 12 months,respectively;there were statistically significant differences (x2 =44.867,68.802,all P ＜ 0.001).Conclusions Initial ALC is an independent effecting factor in the prognosis of children with ITP.Initial ALC could be used for stratifying patients with the infection history before 6 weeks and supposed to be a predictive index for the prognosis of ITP in children.

Prediction of infections within 6 months of the initial diagnosis in adults with immune thrombocytopenia by absolute lymphocyte count / 中华血液学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</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 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>