A case of severe neonatal thrombocytopenia with schizencephaly associated with anti-HPA-1 b and anti-HPA-2a

We report a family with a neonate who was severely damaged by intracranial haemorrhages. These probably occurred before the 20th week of gestation. The neonate had a moderate thrombocytopenia. In the maternal serum anti-HPA-1b and anti-HPA-2a alloantibodies were detected. Third-generation assays were applied to identify the alloantibodies. No other cause for the bleeding was found. Probably the combination of anti-HPA-1b and anti-HPA-2a alloantibodies, directed against the platelet fibrinogen receptor and the von Willebrand receptor, respectively, induced a thrombocytopenia and a thrombocytopathy.     

Failure of the platelet-activating-factor antagonist WEB 2086 BS for treatment of chronic autoimmune thrombocytopenia

Summary Thirteen patients with chronic autoimmune thrombocytopenia (AITP) were treated for 14 days with daily oral doses of 120 mg of the novel platelet-activating-factor (PAF) antagonist WEB 2086 BS. Clinical bleeding symptoms remained essentially unchanged in 9 patients and became more pronounced in the post-treatment period in 4 patients. In no case was an increase in platelet counts observed. While the PAF antagonist was well tolerated subjectively during treatment, most patients exhibited a prolongation of the sensitive hemostasis time (a modified bleeding time test) after treatment, but the Duke bleeding time was not changed. We conclude that the PAF antagonist WEB 2086 BS is ineffective for treatment of chronic AITP and should be used with caution in thrombocytopenic patients.     

Age as the major predictive factor of long-term response to splenectomy in immune thrombocytopenic purpura

Sixty-one consecutive patients undergoing splenectomy for chronic immune thrombocytopenia were retrospectively evaluated. Platelet response was considered as complete (CR) when platelet count rose to > 100 x 109/l, partial (PR) when 30-100 x 109/l or absent (NR) if otherwise. Follow-up (mean time 7.6 years) was possible in 54 patients. Forty-eight patients (88%) had an immediate response to splenectomy (39 CR, 9 PR) whereas six (12%) were NR. Thirty-six responders (67%) had sustained remission (31 CR; 5 PR) without further treatment; thrombocytopenia recurred in 12 patients (33%). The probability curve of continued remission showed a constant relapse-rate during the first 36 months; a further step of relapse was observed beginning 70 months after surgery. The only positive predictive factor for the long-term response to splenectomy was age < 40 (P < 0.005). Neither duration of thrombocytopenia nor previous response to medical treatment (steroids and/or intravenous immunoglobulins) were related to splenectomy response.     

Powikłania infekcyjne i autoimmunologiczne w przewlekłej białaczce limfocytowej

Profound disturbances of different elements of the immune system in chronic lymphocytic leukemia (CLL) lead to impaired elimination of allogeneic antigens, like pathogenic microorganisms, and deficient tolerance of self-antigens, which is responsible for autoimmunological disorders. Susceptibility to infections in CLL patients is due to disease-related immunodeficiency, mainly hypogammaglobulinemia, and aggravated by myelo- and immunosuppressive properties of currently used antileukemic drugs, especially alkylating agents and purine analogues. Severe infections occur in the majority of CLL patients, they may be life-threatening and shortening the patients’ survival. They affect most frequently the respiratory system, and are caused mainly by Gram-positive and Gram-negative bacteria and common viruses like Herpes and Varicella-Zoster. In some patients, especially those treated with purine analogues, opportunistic infections can occur. There are no generally admitted guidelines for the prophylaxis of infections. Vaccinations against influenza and encapsulated bacteria, intravenous immunoglobulins and prophylaxis with cotrimoxazol and antiviral drugs for selected patients under purine analogues or alemtuzumab have been proposed. Autoimmune hemolytic anemia (AIHA) due to the production of anti-erythrocyte autoantibodies is the most common autoimmunological complication of CLL, especially in patients with positive direct antiglobulin test (DAT). It can be also triggered by alkylating agents and purine analogues. The treatment of AIHA includes corticosteroids, rituximab, immunosuppressive agents and splenectomy. Autoimmune thrombocytopenia, pure red cell aplasia, autoimmune neutropenia and non-hematological autoimmune manifestations can also occur.     

原发免疫性血小板减少症患者CD4+T细胞CD28的表达及其与IFN-γ/IL-10比率的关系

目的 研究原发免疫性血小板减少症(ITP)患者治疗前、后,外周血CD4+的T淋巴细胞中共刺激分子CD28的表达及与IFN-γ/IL-10比率的关系.方法 采用流式细胞术分析30例ITP患者糖皮质激素治疗前、后和26例正常对照外周血CD4+T细胞上CD28表达率,用ELISA双夹心法检测外周血血清中IFN-γ和IL-10的水平,评价CD4+ CD28+与IFN-γ/IL-10平衡状态、血小板计数之间的关系.结果 ITP患者治疗前CD4+ CD28+的表达显著高于正常对照组(P＜0.05),治疗后与正常对照组比较,差异无统计学意义(P>0.05);ITP患者治疗前IFN-γ水平较正常对照组显著增高,IL-10水平显著降低,IFN-γ/IL-10比值显著增高(P＜0.01),治疗后与正常对照组比较,差异无统计学意义(P>0.05);ITP患者治疗前CD4+ CD28+与IFN-γ/IL-10比值呈正相关(P＜0.05),与血小板计数呈负相关(P＜0.05).结论 共刺激分子CD28与ITP免疫紊乱密切相关,可能通过参与Th1优势状态形成而在ITP的发病中发挥一定作用.     

B cell elimination in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution, potentially life-threatening with considerable morbidity. The elimination of pathogenic B cells has emerged as a rational therapeutic option. Many open label studies have reported encouraging results in which clinical and serological remission have invariably been described, often enabling the reduction of steroid and immunosuppressive treatment. However, the results from randomized controlled studies have been disappointing and several questions remain to be answered. In this review we will focus on results of B cell direct depletion in the treatment of patients with systemic lupus erythematosus.     

Carbamazepine-induced immune thrombocytopenia confirmed by modified MASPAT test

A 76-year-old man suffering post-herpetic neuralgia developed severe thrombocytopenia 15 days after the administration of carbamazepine. Carbamazepine-dependent platelet antibodies were proved to be present in the patient’s serum by a modified Monoclonal Antibody Solid-phase Platelet Antibody Test (MASPAT), and the diagnosis of carbamazepine-induced immune thrombocytopenia was confirmed. For the patient, carbamazepine should be advised to be avoided permanently. The present report advocated the application of a modified MASPAT test for the detection of carbamazepine-dependent platelet antibodies.     

蒙特卡洛模拟评价利奈唑胺静脉治疗中国成人休克患者常见革兰阳性菌感染的标准给药方案

目的：蒙特卡洛模拟评价标准给药方案（600 mg/q12h）的利奈唑胺（LIN）静脉治疗中国成人休克患者常见革兰阳性（G⁺）球菌感染的临床有效性与安全性。方法：搜集LIN静脉给药在中国成人休克患者中的群体药动学参数及其对常见G⁺球菌的最低抑菌浓度值（MIC）和其分布频率,分别以24 h血药浓度-时间曲线下面积与MIC之比（AUC_24h/MIC）和稳态最小血药浓度（C_min^SS）作为研究微生物学疗效和临床安全性的目标指数,模拟10 000例次后得到对应目标（AUC_24h/MIC ≥80,C_min^SS<7 mg·L^-1）的达标概率（PTA）。结果：对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和屎肠球菌,仅当MIC≤2 mg·L^-1时方可达满意抗菌活性（PTA=100%）,而对肺炎链球菌,均可达满意抗菌活性（PTA=100%）;C_min^SS与协变量血小板计数呈负相关关系,当C_min^SS <7 mg·L^-1时的PTA为6.53%。结论：对于LIN静脉治疗中国成人休克患者金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和屎肠球菌感染,当MIC≤2 mg·L^-1时,标准给药剂量能获得较好抗菌疗效,而对于肺炎链球菌感染则均可达满意抗菌活性。此类患者标准给药剂量方案下其血小板减少症风险亦较高,必要时应根据临床情况适当减量。     

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。