部分脾栓塞术的临床应用

目的：探讨部分脾栓塞术（PSE）的临床应用。方法：采用PSE治疗肝癌伴脾亢（HCC－HS）86例,其它继发性脾亢（SHS）26例,原发性血小板减少性紫癜（ITP）5例,其中20例行2次以上PSE。结果：平均栓范围HCC－HS组为36％,SHS组为60％,ITP组为74％,临床有效率分别为84．8％、88．5％、100％。HCC－HS组因单次栓塞范围较小,约20．9％（18／86）病人需行再次栓塞。全部病例均未发生严重并发症。结论PSE是安全有效,可作为外科脾切除的替代疗法,HCC－HS组为了减轻术后并发症PSE可分次进行。     

特发性血小板减少性紫癜脾切除术后早期并发症

目的 评估脾切除治疗特发性血小板减少性紫癜（ＩＴＰ）的安全性。方法 回顾分析了１６７例ＩＴＰ选择性脾切除术的术后早期并发症。结果 １４例（８．３８％）病人出现１７例次术后早期并发症;切口感染７例,腹腔大出血２例,颅内出血２例,膈下脓肿１例,肺感染１例,应激性高血糖反应４例。２例（１．２０％）术后并发颅内出血死亡。结论 选择性脾切除术是ＩＴＰ一种安全的治疗手段。     

地塞米松、环孢素A对慢性特发性血小板减少性紫癜患者淋巴细胞凋亡的影响

目的研究在体外条件下,地塞米松和环孢素A对慢性特发性血小板减少性紫癜患者外周血淋巴细胞凋亡的影响。方法用流式细胞仪测经地塞米松和环孢素A处理过的慢性特发性血小板减少性紫癜患者淋巴细胞凋亡率。结果用地塞米松、环孢素A处理过的慢性特发性血小板减少性紫癜患者淋巴细胞凋亡率明显高于对照组（P〈0．01）。结论地塞米松和环孢素A能增加慢性特发性血小板减少性紫癜患者淋巴细胞凋亡,是有效的免疫抑制药物,能针对慢性特发性血小板减少性紫癜患者细胞免疫异常的发病机制进行治疗。     

High-dose dexamethasone regulates interleukin-18 and interleukin-18 binding protein in idiopathic thrombocytopenic purpura

To evaluate the effects of high-dose dexamethasone (HD-DXM) on the balance of interleukin-18 (IL-18) and its endogenous antagonist IL-18 binding protein (IL-18BP) in ITP patients, IL-18, IL-18BP as well as IFN-γ, IL-4 plasma levels and platelet counts were determined in 17 ITP patients receiving DXM 40 mg/day for four consecutive days and in 24 healthy subjects. Using RT-PCR, the mRNA expression of IL-18, IL-18BP, IFN-γ, IL-4, T-box (T-bet) and GATA-binding protein 3(GATA-3) were studied in all subjects. The in vitro effects of DXM on IL-18BP and IL-18 of peripheral blood mononuclear cells (PBMCs) were studied by ELISA. HD-DXM administration increased IL-18BP and reduced IL-18 expression significantly (p<0.05), which resulted in a downregulation of IL-18/IL-18BP ratio p<0.05). In vitro, DXM had a significant effect on secretion of IL-18BP while diminishing IL-18 release from cultures of PBMCs. These results suggest that downregulation of IL-18/IL-18BP might account for its clinical efficacy of HD-DXM in active ITP.     

Full neurologic recovery after fulminant thrombotic thrombocytopenic purpura with status epilepticus

Thrombotic thrombocytopenic purpura (TTP) is an ischemic vasculopathy frequently associated with neurological dysfunction including seizures. However, status epilepticus (SE) has rarely been reported in this condition. We report on a 70-year-old woman with fulminant TTP who developed convulsive SE despite high therapeutic serum levels of phenytoin and phenobarbital. Her electroencephalogram (EEG) was characterized by bilateral independent periodic lateralizing epileptiform discharges (BIPLEDs) propagating into clinical and electrographic seizures. She recovered completely after intensive plasmapheresis and treatment with pentobarbital induced coma for 5 days. This case illustrates that aggressive treatment with pentobarbital and plasmapheresis may prevent permanent neurologic deficits when TTP is complicated by SE and that periodic lateralizing epileptiform discharges (PLEDs) in this syndrome can be the manifestation of a reversible ischemic insult.     

间充质干细胞体外对ITP患者T淋巴细胞分泌功能的影响

目的： 体外观察间充质干细胞（MSCs）对特发性血小板减少性紫癜（ITP）患者T淋巴细胞分泌细胞因子功能的影响。方法: 采用Ficoll分离和体外贴壁、传代培养,扩增出骨髓MSCs;通过Ficoll分离法和尼龙棉柱法获取ITP患者外周血T淋巴细胞。以经丝裂霉素（MMC）处理后不同数量（2×103、1×104、5×104 cells/well）的MSCs作为基底层细胞,接种体外分离纯化的异体ITP患者T淋巴细胞,分别于2 d、4 d、6 d后各自收集培养上清,用酶联免疫吸附试验(ELISA)法动态测定T淋巴细胞分泌白细胞介素2(IL-2)、干扰素-γ(IFN-γ)、白细胞介素4(IL-4)、白细胞介素10(IL-10)水平的变化。结果: ITP患者T淋巴细胞分泌细胞因子IL-2、IFN-γ较正常人高(P<0.05),IL-4、IL-10较正常人低(P<0.05)。MSCs可显著抑制ITP患者或正常对照组T淋巴细胞分泌IL-2、IFN-γ(P<0.05),且随MSCs数量的增加,抑制增强(P<0.05),共培养4 d、6 d时作用明显强于2 d时(P<0.05);MSCs可促进ITP患者T淋巴细胞分泌IL-4、IL-10 (P<0.05),且随MSCs量的增加,促进作用增强(P<0.05),对IL-10的作用随时间延长而增强(P<0.05),但对IL-4的作用在培养第2 d、4 d、6 d时无显著差异(P>0.05);在正常对照组,当MSCs数量>1×104可以促进T淋巴细胞分泌IL-4 与IL-10 (P<0.05),且随MSCs数量的增加,作用增强(P<0.05),共培养4 d、6 d时作用明显强于2 d时(P<0.05)。结论: MSCs能够在体外调节ITP患者辅助性T细胞1 (Thl)和辅助性T细胞2 (Th2)反应平衡,可使ITP患者Th1极化状态部分改善。     

Role of metalloproteinases in platelet function

Platelets contain and release matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and disintegrin metalloproteinases (ADAMs) including MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP (MMP-14), ADAM-10, ADAM-17, ADAMTS-13, TIMP-1, TIMP-2 and TIMP-4. These proteins exert several effects regulating platelet functions such as agonist-stimulated platelet adhesion and aggregation, tumour cell-induced platelet aggregation and platelet-leukocyte aggregation. In this review, mechanisms of MMPs, TIMPs and ADAMs on platelets are discussed.     

Platelet apoptosis resistance and increased CXCR4 expression in pediatric patients with chronic immune thrombocytopenic purpura

The pathogenesis of childhood chronic immune thrombocytopenic purpura (ITP) is mainly mediated by antiplatelet autoantibodies, which have been shown to induce platelet apoptosis in murine models. Decreased CXCR4 expression, which can regulate apoptotic pathway, has been described in platelet disorders. The present study aims to determine whether platelet apoptosis is increased in pediatric patients with chronic ITP and whether there is any involvement of the CXCR4 chemokines axis. Twenty-one patients and 12 controls were studied. Using flow cytometry, we investigated apoptotic markers of platelets including annexin V, caspase 3, and mitochondrial inner transmembrane potential depolarization. The percentage of the platelets with apoptosis-positive markers was not increased in chronic ITP patients. CXCR4 expression was higher in the patients as detected by flow cytometric (P = 0.001) and western blotting analysis (P = 0.013). The results also revealed that CXCR4 downstream proteins, Akt phosphorylation was more frequent in chronic ITP patients than controls. Plasma stromal cell-derived factor 1 levels analyzed by enzyme-linked immunosorbent assay were decreased in patients (P = 0.001) and inversely correlated to CXCR4 expression (r = -0.62, P < 0.001). In conclusion, the study shows platelet apoptosis resistance existing in pediatric patients with chronic ITP. It may be associated with enhanced CXCR4 expression and Akt activation.     

Efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome

Introduction

Hemolytic uremic syndrome is a thrombotic microangiopathy. Clopidogrel, a recently developed platelet aggregation inhibitor, has not been previously reported as a treatment for this illness. Our study's objective was to explore the efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome.

Materials and Methods

We performed a retrospective chart review of all children (≤ 18 years) hospitalized with diarrhea associated hemolytic uremic syndrome. Outcomes in clopidogrel treated children were described. In subgroup analysis, outcomes were compared to those untreated with platelet aggregation inhibitors.

Results

Of 72 children with diarrhea associated hemolytic uremic syndrome, 88% were treated with platelet aggregation inhibitors (clopidogrel 56%, sulfinpyrazone 19%, dipyridamole 13%). The median age of clopidogrel treated children was 5 years; 40% were male. Initial median hemoglobin, platelet count, and serum creatinine were 10.1 g/dL, 53 × 10³/μL, and 2.3 mg/dL respectively. Clopidogrel (median dose 1 mg/kg/d) was given for a median of 4 days (range 1-15). Other therapies included erythropoietin (98%), red blood cell transfusions (80%), diuretics (58%), anti-hypertensive agents (45%), and dialysis (33%). The median hospital length of stay was 9 days (range 3-26). Three children had bleeding complications (epistaxis/hematemesis). The risk of chronic kidney disease was 5% and death 2.5%. In subgroup analysis, median duration of dialysis was 11 days in thirteen clopidogrel treated children compared to 21 days in five untreated patients (P = 0.04).

Conclusions

Children with diarrhea associated hemolytic uremic syndrome treated with clopidogrel have outcomes comparable to untreated patients. Bleeding complications may occur.