Use of recombinant factor VIIa (rFVIIa) to control intraoperative bleeding in pediatric brain tumor patients

Surgical bleeding during the resection of brain tumors in children may be related to tumor vascularity, pathology, and location. Despite improvements in neurosurgical technique, neuroanesthesia, and blood product replacement, bleeding can be life-threatening in these surgeries. We report eight pediatric patients in whom recombinant factor VIIa (rFVIIa) was used to control intraoperative bleeding during surgical resection of pediatric brain tumors. rFVIIa should be considered as a method to control intraoperative bleeding that is unresponsive to conventional interventions. Additional studies are needed to determine optimal patient selection and drug dosing, efficacy and safety.     

Successful treatment of acute lymphoblastic leukemia with L-asparaginase-induced intracranial hemorrhage to activated recombinant factor VIIa in a child

L-Asparaginase, a major component of therapy in children with acute lymphoblastic leukemia, has been shown to induce coagulopathy by inhibiting synthesis of clot-forming and clot-inhibitory proteins. The authors report the successful use of recombinant factor VIIa in a 15-year-old girl with acute lymphoblastic leukemia who had L-asparaginase-induced intracranial hemorrhage. The present case is the first to demonstrate use of rFVIIa in L-asparaginase-induced intracranial hemorrhage in a child with acute lymphoblastic leukemia.     

Successful use of recombinant factor VIIa for management of severe menorrhagia in an adolescent with an acquired inhibitor of human thrombin

Antibodies directed against human thrombin are exceedingly rare, having only been reported in adult patients with underlying diseases. Consensus on the most appropriate management has not yet been reached. A 12-y-old girl presented with intractable menorrhagia several days after an acute infectious episode. Laboratory tests revealed disturbed clotting tests: prothrombin index 17%, activated partial thromboplastin time >150 s, thrombin time >120 s, and failure to achieve correction with a normal pooled plasma. Further studies demonstrated the presence of an antibody directed against human thrombin. Viral serology revealed a 1/128 titre for adenovirus. Massive haemorrhage was unresponsive to standard treatments, but intravenous administration of recombinant factor VIIa resulted in a successful outcome. Conclusion: This is the first report of an anti-human thrombin antibody associated with severe bleeding in a child. Recombinant factor VIIa could represent a novel therapeutic approach for such patients.     

儿童噬血细胞综合征11例临床分析

目的探讨儿童噬血细胞综合征(HLH)的临床特点及诊治策略。方法回顾性分析2009至2013年住院治疗的11例HLH患儿的临床资料。结果 11例患儿中,6例为EB病毒感染相关性HLH,1例为T细胞淋巴瘤相关性HLH,2例病因不明,2例为UNC13D基因编码序列突变,分别为c.2459CT/p.A832V(丙氨酸突变为缬氨酸),c.3067CT/p.R1023C(精氨酸突变为半胱氨酸);11例患儿中6例经治疗后病情好转,5例治疗无效死亡。结论儿童HLH临床表现缺乏特异性,病情发展快,须及时诊断、治疗。     

儿童噬血细胞综合征68例临床研究

目的探讨儿童噬血细胞综合征(HPS)的临床特点、诊断、治疗及预后。方法回顾分析2002年1月至2007年6月广东省9所医院诊治的68例儿童HPS的临床特点、治疗及预后。结果68例病例中放弃治疗16例(23.5%),死亡9例(13.2%)。2005年前治疗者共4例,1例完全缓解后失访,余3例死亡。2005年后(釆用HLH-04方案)治疗痊愈20例(20/42,47.6%),完全缓解继续治疗中4例(9.5%),完全缓解后失访6例(14.3%),复发治疗中5例(11.9%)。结论广东地区儿童HPS的发病有逐年增多的趋势;其原发病最常见为EBV感染;采用HLH-04方案治疗后疗效有所提高。     

儿童噬血细胞综合征死亡相关因素分析

目的探讨儿童噬血细胞综合征(HPS)死亡的相关因素,以提高临床医师对其认识,为降低病死率提供可借鉴的经验。方法采用回顾性病例对照研究方法,对HPS死亡患儿(死亡组)和存活患儿(存活组)进行分析比较,对可能与HPS死亡相关的危险因素进行分析。结果46例HPS患儿中,死亡11例,存活35例,病死率23.9%。11例死亡病例中,死于多脏器功能衰竭4例,呼吸循环衰竭3例,感染2例,中枢系统浸润1例,弥散性血管内凝血1例。统计学分析显示,HPS患儿死亡危险因素包括年龄(χ2=6.273,P0.05)、中枢神经系统症状(χ2=16.27,P0.01)、骨髓增生低下(χ2=7.232,P0.05)、谷草转氨酶(AST)400 U/L(χ2=4.927,P0.05)、乳酸脱氢酶(LDH)1 000 U/L(χ2=5.855,P0.05)、治疗方案(χ2=11.266,P0.05)。结论HPS患儿死亡与多种因素相关,及早诊断、治疗对提高HPS患儿生存率至关重要。     

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目的了解穿孔素基因(PRF1)突变和序列变异在中国儿童噬血细胞综合征(HLH)中的发生情况,探讨基因突变型与临床表现之间可能的关系。方法应用聚合酶链反应(PCR)结合直接测序方法,对2006年1月至2008年5月在首都医科大学附属北京儿童医院治疗的临床诊断为HLH的30例患儿(HLH组)及50名新生儿(对照组)PRF1基因外显子编码区进行突变筛查。结果在3例HLH患儿的PRF1基因外显子编码区发现3个杂合错义突变,这3个突变均导致氨基酸改变(C102F、S108N和T450M),而在对照组中却未发现。1例患儿为复合杂合错义突变(S108N和T450M),从遗传学上可明确诊断为家族性HLH亚型2(FHL2);1个同义序列变异(Q540Q)在1例患儿中发现,而在对照组中未发现;在HLH组和对照组的PRF1基因编码区发现2个单核苷酸多态位点(SNP)(A274A、H300H),但这2个SNP的基因型频率在HLH组和对照组之间的分布差异无统计学意义(P均>0.05)。结论我国HLH患儿中存在PRF1基因突变,而突变位点(C102F和S108N)目前仅在中国患儿中发现。显示了我国HLH患儿PRF1基因突变具有自身的特点...     

Successful management of bleeding with recombinant factor VIIa (NovoSeven) in a patient with Burkitt lymphoma and thrombosis of the left femoral and left common iliac veins

We present the case of an 18-year-old female with Burkitt lymphoma involving the intra-abdominal and inguinal lymph nodes. The tumor had invaded the left femoral and common iliac veins causing secondary thrombosis and vessel occlusion. Chemotherapy and anticoagulant treatment resulted in mild thrombocytopenia and a prolonged prothrombin time, respectively, which exacerbated postoperative bleeding following surgical removal of a deep inguinal necrosis. After 6 days, bleeding combined with epistaxis was considered to be life threatening and anticoagulant reversal with recombinant factor VIIa was successfully performed. The patient has since achieved complete remission and subsequent antithrombotic therapy has resolved the vascular occlusion.     

Management of coagulopathy with recombinant factor VIIa in a neonate with echovirus type 7

A 5-day-old newborn presented with neonatal enteroviral infection. The patient's hospital course was complicated by acute liver dysfunction, renal insufficiency, fluid overload, respiratory failure, hypertension, catheter related thrombosis, Klebsiella pneumoniae sepsis, intracerebral and intraventricular hemorrhage, and disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) and cryoprecipitate failed to control the patient's hemostasis and led to significant fluid overload. Recombinant activated factor VII (rFVIIa, Novoseven NovoNordisk, Bagsvaerd, Denmark) was given to the neonate as a bolus (rFVIIa at 60-80 microg/kg body weight), followed by a continuous infusion (2.5-16 microg/kg/hr). Recombinant activated factor VII controlled hemostasis, until the patient's liver function recovered. The patient's blood product requirement significantly decreased and his fluid overload resolved. Administration of rFVIIa appears to have stabilized the coagulation process. The patient appears to have fully recovered from the infection's complications.     

儿童噬血细胞综合征28例临床特点和预后分析

目的 探讨小儿噬血细胞综合征的临床特点、诊断、治疗以及预后的危险因素.方法 回顾分析了近10年在我科收治的28例儿童噬血细胞综合征(HPS)的病因、临床表现、实验室检查、治疗转归,采用Logistic回归方法分析患儿的预后危险因素.结果 28例中18例(64.3%)与感染相关,其中EB病毒相关性噬血细胞综合征最多;余10例中2例(7.14%)与非感染相关,8例(28.6%)病因不明.临床症状以持续高热(100%)、肝脏肿大(89.3%)、脾脏肿大(82.1%),浅表淋巴结肿大(78.6%)为突出表现.血常规检查示外周血白细胞计数减少(85.7%)、血红蛋白减少(67.9%)、血小板减少(64.3%);血生化检查肝功能异常90.5%,血清三酰甘油升高46.4%,凝血功能异常42.9%,血清铁蛋白升高39.3%,骨髓检查找到噬血细胞96.4%.28例中死亡9例(32.1%),好转或痊愈11例(39.3%),出院后失访8例(28.6%).患儿年龄<2岁、乳酸脱氢酶(LDH)>2 000 U/L是预后危险因素.结论 儿童噬血细胞综合征病因复杂,临床表现多样,病死率较高.年龄、LDH水平是影响HPS预后的不良危险因素.     

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??Objective??To investigate the clinical diagnosis treatment and prognosis of young children infected by leishmania with hemophagocytic syndrome ??HPS?? in Xinjiang. Methods??During December 2007and December 2009??16 patients of young children with HPS were hospitalized in the Pediatric Department of the People’s Hospital??Xinjiang Uyghur Autonomous Region. The data of patients’ habitation?? clinical presentation and laboratory results were reviewed and analyzed. Results??All the 16 patients came from the Tarim Basin in Xinjiang and the diagnosis was supported by laboratory tests. In nine patients??Lidou body ??Leishmania donovani?? were found in bone marrow??and in fourteen patients??serum rK39-ELISA ??rK39?? Leishmania donovani gene expression product?? ELISA?? enzyme-linked immunosorbent assay?? test was positive. The first two cases among these16 patients were misdiagnosed as familial HPS??who had no response to the treatment and died. The other 14 cases were diagnosed as Assam fever caused by visceral leishmania??and sodium antimony gluconate was administered. Fourteenpatients were cured. Conclusion??In the Tarim Basin??in young patients with HPS the visceral leishmania infection should first be considered. Serum rK39-ELISA test is helpful in the diagnosis of Leishmania infection. The HPS Assam fever in young children is often emergent and severe ??the children would die quickly unless an early diagnosis were made and appropriate treatment were given.     

Recombinant factor VIIa in an infant with haemophilia A and inhibitors

Post-traumatic bleeding from the gingiva in a 16-month-old boy with severe haemophilia A did not stop after treatment with factor VIII concentrate and tranexamic acid, and it was demonstrated that he had developed antibodies to factor VIII. Treatment with recombinant factor VIIa 60-90 micrograms/kg body weight four to eight times daily, together with local measures, stopped the bleeding and no complications were seen.     

儿童EB病毒相关噬血细胞综合征14例临床分析

目的探讨EB病毒相关噬血细胞综合征(EBV-AHS)的病因、临床表现、治疗及预后。方法对14例EBV-AHS临床资料进行分析。结果EBV-AHS临床表现多为高热,肝、脾、淋巴结肿大,出血,皮疹等。血细胞有不同程度减少,血清铁蛋白增高,乳酸脱氢酶(LDH)显著增高,骨髓中出现噬血细胞。联合化疗(环孢素A+足叶乙苷)、糖皮质激素、静脉丙种球蛋白(IVIG)治疗有效。结论EBV-AHS病因复杂,病情凶险,病死率高,联合化疗、糖皮质激素、IVIG治疗有效。     

EB病毒相关噬血细胞综合征并重症肝炎1例报告

目的探讨EB病毒相关噬血细胞综合征的临床与病理特征。方法回顾性分析1例EB病毒相关噬血细胞综合征并重症肝炎死亡病例的临床资料,复习相关文献。结果患儿1岁2个月,有发热、血细胞减少、纤维蛋白原、自然杀伤细胞下降、血清铁蛋白及三酰甘油升高;血涂片异常淋巴细胞占5%;EBV-DNA荧光定量检测1.39×108拷贝/ml;尸检结果提示死亡原因为多脏器功能衰竭;肝脏组织行EB病毒编码RNAs(EBERs)原位杂交检测,约30%淋巴细胞中EBERs阳性,肝细胞EBERs阴性。结论该例患儿确认EB病毒相关噬血细胞综合征,累及多器官,其中肝损伤并非EB病毒直接感染所致。     

儿童伤寒并发噬血细胞综合征 1 例临床分析

目的分析儿童伤寒并发噬血细胞综合征(Ty-AHS)的临床特点和转归。方法回顾分析1例Ty-AHS患儿的临床资料,并复习相关文献。结果患儿,男,4岁,持续腹泻、高热与低体温交替、表情淡漠、肝脾肿大、急性腹膜炎表现、腹腔积液。血常规示嗜酸性粒细胞为0,血红蛋白、血小板明显下降,C反应蛋白、降钙素原明显升高,血浆纤维蛋白原下降至0.8 g/L,乳酸脱氢酶升高3 835 U/L,血清铁蛋白1 884 ng/mL,血三酰甘油2.42 mmol/L,血EBV-DNA滴度2.81×10~4/m L,血培养伤寒沙门菌血清型Ⅲb;腹部彩超提示肠系膜淋巴结增大,中量腹腔积液;胸片提示肺炎;淋巴细胞分析示CD4~+/CD8~+比值降低,CD3~-CD16~+56~+细胞降低,CD19~+细胞降低;骨髓细胞学检查,骨髓增生明显活跃,粒、红、巨三系均未见明显异常,全片见较多组织细胞及噬血组织细胞。给予抗感染,地塞米松治疗2周后患儿症状消失,体征和实验室检查渐恢复正常。结论儿童Ty-AHS是一种罕见并发症,起病急,进展快,抗生素加激素治疗有效。     

EB病毒相关性噬血细胞综合征的临床特征及外周血淋巴细胞亚群的变化

目的 分析EB病毒相关性噬血细胞综合征(EBV-AHS)患儿的临床特点,了解其外周血淋巴细胞亚群的变化.方法 20例EBV-AHS患儿,均符合噬血细胞综合征的诊断标准,并有EBV感染的证据,对其临床特点进行总结分析,并采用流式细胞术检测外周血淋巴细胞亚群CD4+、CD8+、CD19+、CD16+CD56+、CD4+/CD8+的水平.选择20例健康儿童作为对照组.结果 在EBV-AHS的诊断标准中,以发热、血常规2系以上降低、乳酸脱氢酶升高(＞1 000 U/L)、高密度脂蛋白降低及铁蛋白增高(＞1 500 g/L)5项指标异常发生率最高,均为100%.与对照组相比,EBV-AHS患儿外周血CD8+T及CD19+B细胞比例增高(分别为53.70% ±10.6% vs 27.05% ±8.22%,24.95% ±5.34% vs11.85% ±4.53%),而CD4+T及CD16+CD56+NK细胞比例下降(分别为23.60% ±6.42% vs 45.20% ±5.74%,5.55% ±2.87% vs 14.70% ±4.16%),CD4+/CD8+比值降低(0.46±0.16 vs 1.84±0.68),差异均有显著性(P＜0.01).结论 EBV-AHS患儿细胞及体液免疫功能发生紊乱,导致了疾病的发生发展.     

Increasing values of serum acid phosphatase in a child with Mycoplasma pneumoniae-associated hemophagocytic histiocytic syndrome

We describe a 3 1/2-year-old boy with disseminated histiocytic disease probably induced by Mycoplasma pneumoniae. In this patient, acid phosphatase was elevated in serum and was also detected histochemically in the infiltrating histiocytes. The serum acid phosphatase levels increased as his his tiocytosis progressed, apparently mirroring the activity of the disease. This observation suggests that serum acid phosphatase levels should be evaluated further to determine whether they will be a useful indicator of disease in children with different histiocytosis syndromes. © 1993 Wiley-Liss, Inc.     

Hematopoietic stem cell transplantation in children with Griscelli syndrome: A single‐center experience

GS2 is a rare autosomal recessive disease characterized by hypopigmentation, variable immunodeficiency with HLH. HSCT is the only curative treatment for GS2. We analyzed the outcome of 10 children with GS2 who underwent HSCT at our center between October 1997 and September 2013. The median age of the patients at transplant was 13.5 months (range, 6‐58 months). All of the patients developed HLH before HSCT and received HLH 94 or HLH 2004 protocols. Donors were HLA‐identical relatives in 8 patients, HLA‐mismatched relatives in 2 patients. Engraftment was achieved in all except one patient. None of the patients developed acute GVHD. Chronic GVHD occurred in one and veno‐occlusive disease occurred in four patients. Eight of the patients are under remission without any neurologic sequelae—median time of disease‐free survival is 92.4 months. The present study shows successful transplant outcome without long‐term neurologic sequelae in patients with GS2 who underwent HSCT from HLA‐related donors.