Logistic模型联合ROC曲线对利奈唑胺致老年患者血小板减少的预测分析

目的：采用Logistic模型和ROC曲线探讨老年患者接受利奈唑胺治疗引起血小板减少的相关危险因素,并预测该人群中不良反应的发生风险。方法：回顾性分析某院2018年3月至2019年9月期间接受利奈唑胺治疗老年患者的临床资料,收集患者的基本信息、实验室指标、联合用药和不良反应的情况。采用多因素Logistic回归法分析接受利奈唑胺治疗的老年患者发生血小板减少症的危险因素,通过建立Logistic模型,并联合ROC曲线对血小板减少症的发生情况进行预测分析。结果：102例患者（男性68名,女性34名）纳入研究,利奈唑胺治疗期间23例（22.5%）发生血小板减少症。多因素Logistic回归分析显示用药时间,血肌酐浓度和血小板基线值是发生血小板减少症的独立危险因素。分别用上述独立危险因素建立Logistic回归方程,经变换后得到联合预测因子的计算公式,Y联合=X_Scr+34.0X_T-1.6X_PLT,联合预测因子的ROC曲线下面积（0.821,95%CI：0.755~0.866,P<0.001）优于其他指标,具有一定的预测价值,Youden指数最大时（0.606）的切点为ROC曲线上的最佳界值（183.7）。结论：用药时间、基线血小板值、血肌酐浓度是利奈唑胺致老年患者血小板减少的独立危险因素,临床用药期间,可将上述因素带入联合预测因子的计算公式,预测发生血小板减少症的风险,以便及时调整给药方案。     

Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation

The use of HSCT is the only potentially curative treatment for CAMT, but access is limited by the availability of suitable donors. We report five consecutive patients with CAMT who received MAC and partially HLA‐mismatched, UCBT (unrelated, n = 4). Median times to neutrophil (>500/μL) and platelet (≥20 000 and ≥50 000/μL) engraftment were 19, 57, and 70 days, respectively. Acute GvHD, grade II, developed in one patient, who subsequently developed limited chronic GvHD. At median follow‐up of 14 yr, all patients are alive with sustained donor cell engraftment. To our knowledge, this is the largest single‐center series of UCBT for patients with this disease and suggests that UCBT is a successful curative option for patients with CAMT.     

血小板生成素在慢性乙型肝炎血小板减少症中的作用

目的：探讨血小板生成素在慢性乙型肝炎血小板减少症患者中的作用。方法：对76例慢性乙型肝炎血小板减少症患者进行血清血小板生成素水平、凝血酶原活动度、骨髓巨核细胞计数检查。结果：血小板生成素水平与凝血酶原活动度、骨髓巨核细胞计数、外周血小板计数相关（r分别为0．423、0.396、0．297，P〈0．05）；76例患者标本中有22例骨髓巨核细胞计数〈7（个／4．5cm^2），占20％；巨核细胞成熟障碍29例，占38％。结论：血小板生成素在慢性乙型肝炎血小板减少症的发病机制中起一定作用。     

Heparin-induced thrombocytopenia and thrombosis: a prospective analysis of the incidence in patients with heart and cerebrovascular diseases

Heparin-induced thrombocytopenia and/or thrombosis (HITT) are serious complications of heparin treatment. The incidence, as previously reported, varies widely and, in consequence, is not precisely known. Moreover, most reports only concern clinically defined heparin-induced thrombocytopenia. Therefore we carried out a prospective study of the incidence of serologically confirmed HITT.
All patients admitted to the Departments of Cardiology and Neurology of our institution with an indication for treatment with therapeutic-dose intravenous unfractionated heparin were enrolled in the study. The patients were examined daily for the occurrence of thromboembolic complications. Regular platelet counts and tests for the presence of heparin-dependent antibodies were carried out using two different tests: a quantitative platelet factor 4/heparin (PF4/hep) Elisa, and a functional test, the heparin-induced platelet activation assay (HIPAA). HITT was defined as a rapidly occurring (within 5 d) decrease of the platelet count from normal values of >120 ×10⁹ l to <60 ×10⁹ l or to <100 ×10⁹ l if there was a rapid fall of >50% of starting value or >30% with concomitant acute thrombosis.
The observed incidence of HITT was 1/358 patients (0.3%, 95% confidence limits 0.01–1.5%). However, Elisa PF4/hep specific IgG antibodes were demonstrated in nine (2.5%) and IgM antibodies in seven (2.0%) of 358 patients. 30/358 patients (8.4%) had platelet activating antibodies in the HIPAA.
We conclude that the incidence of serologically confirmed HITT in this study is very low (0.3%) in patients with cardiac and neurologic diseases treated with intravenous unfractionated heparin. The frequency of heparin-dependent antibodies without concomitant occurrence of thrombocytopenia is much higher.     

Cytokine profile of patients with chronic immune thrombocytopenia affects platelet count recovery after Helicobacter pylori eradication

Helicobacter pylori eradication induces platelet recovery in a subgroup of patients with chronic immune thrombocytopenia (cITP), but the mechanisms involved are still not understood. We aimed to evaluate the effect of H. pylori eradication on platelet response and to identify the associated serum cytokine profile in 95 patients with cITP. Serum cytokine concentrations were determined by enzyme‐linked immunosorbent assay prior to and 6 months after H. pylori eradication. Remission of cITP was observed in 17 (28·8%) of 59 patients in whom the bacterium was eradicated. Six months after treatment, a significant reduction in the concentrations of T‐helper (Th) 1 and Th17 cells and an increase in T regulatory (Treg) and Th2‐cell commitment cytokines were observed in patients who recovered, but not in those whose platelet count did not recover. Patients who had a platelet response to eradication of the bacteria had higher pre‐treatment serum levels of γ‐interferon (IFNG, IFN‐γ), transforming growth factor‐β (TGFB1, TGF‐β) and interleukin 17 (IL17A, IL‐17) than patients who did not respond, but only higher pre‐treatment TGFB1 levels was independently associated with platelet response. In conclusion, amelioration of cITP after eradication of H. pylori was linked to a more efficient suppression of Th1 and Th17 response and a more pronounced Treg cell response.     

In vitro TNF blockade enhances ex vivo expansion of regulatory T cells in patients with immune thrombocytopenia

Tumour necrosis factor‐α (TNF) is an inflammatory cytokine that is elevated in a number of autoimmune diseases including immune thrombocytopenia (ITP), a bleeding disorder characterized by low platelet counts. In vitro TNF blockade increases expansion of the regulatory T cell (Treg) IKZF2 (also termed Helios) subset in T cell‐monocyte cocultures from healthy donors, but its role on proliferative responses of Tregs in ITP patients, who have altered immunoregulatory compartment, remains unclear. TNF in CD4+ T cells from patients with chronic ITP were elevated and negatively correlated with peripheral Treg frequencies, suggesting a possible inhibitory effect of TNF on ITP Tregs. In vitro antibody neutralization with anti‐TNF in T cell‐monocyte cocultures resulted in a robust expansion of pre‐existing ITP Tregs, higher than in healthy controls. Similar to the effects of anti‐TNF antibodies, TNF blockade with antibodies against TNFRSF1B (anti‐TNFRSF1B, previously termed anti‐TNFRII) almost doubled ITP Treg expansion whereas neutralization with anti‐TNFRSF1A (anti‐TNFRI) antibodies had no effect on proliferative responses of Tregs. In addition, TNFRSF1B levels on ITP Tregs were significantly elevated, which may explain the increased susceptibility of patient Tregs to the actions of TNF blockade. Altogether, these data raise the possibility that TNF blockers, through their ability to increase Treg proliferation, may be efficacious in ITP patients.     

重组人白介素-11联合环孢素治疗糖皮质激素无效ITP的临床研究

目的：探讨重组人白介素-11(rhIL-11)联合环孢素治疗糖皮质激素无效的原发免疫性血小板减少症(ITP)的远期临床疗效及其安全性。方法选取糖皮质激素治疗无效的ITP患者60例,患者随机分为治疗组(40例)和对照组(20例)。治疗组应用rhIL-11和环孢素治疗,对照组长春新碱和静脉注射用免疫球蛋白治疗,分别在治疗前、后检测两组血小板计数,观察两组临床疗效和不良反应。结果治疗组第1个月、3个月、5个月、12个月末的有效率分别为82．5%、80．0%、72．5%和52．5%,对照组的有效率分别为55．0%、50．0%、40．0%和25．0%,治疗组均优于对照组,差异有统计学意义(P<0．05)。治疗组、对照组不良反应轻微,大多数患者耐受良好。结论 rhIL-11联合环孢素治疗糖皮质激素无效的ITP的中远期疗效满意,安全性良好,可作为理想的二线方案。     

Role of platelets in chronic liver disease and acute liver injury

Platelets contain not only hemostatic factors but also many growth factors that play important roles in wound healing and tissue repair. Platelets have already been used for the promotion of tissue regeneration in the clinical setting, such as dental implantation and plastic surgery. Thrombocytopenia, which is frequently found in patients with chronic liver disease and cirrhosis, is due to various causes such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism. However, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in chronic liver disease are poorly understood. In acute liver injury, it is reported that platelets are recruited to the liver and contribute to liver damage by promoting the induction of chemotactic factors and the accumulation of leukocytes in the liver, whereas platelets or mediators released by platelets can have a protective effect against liver injury. In this review, we highlight the recent accumulated knowledge concerning the role of platelets in chronic liver disease and acute liver injury.     

How Can I Manage Thrombocytopenia in Hemodialysis Patient? A Review

Hemodialysis (HD) is the most important treatment for patients with end‐stage renal disease (ESRD). Thrombocytopenia is a potential treatment complication related to dialysis. Under normal circumstances, the platelet count would slightly decrease within the first hour of HD, but get restored towards the end of procedure. In most patients, the platelet count can be maintained within the normal range, and the occurrence of thrombocytopenia is relatively rare in clinical practice. Therefore, the possibility of thrombocytopenia in HD patients is often ignored. Moreover, thrombocytopenia might be misdiagnosed and mistreated. At present, almost all articles on the subject, apart from some case reports, focus on pseudothrombocytopenia and heparin‐induced thrombocytopenia. In this review, we summarized various underlying causes, mechanisms, and diagnostic approaches to thrombocytopenia in HD patients. The review aims to provide a guide for clinicians interested in the causes and adequate treatment of thrombocytopenia.