Successful treatment of recurrent thrombotic thrombocytopenic purpura with plasmapheresis and vincristine

An adolescent girl with severe thrombotic thrombocytopenic purpura (TTP) remained in a critical condition after 3, weeks of combined treatment with antiplatelet drugs, plasma infusions and plasma exchange. The introduction of vincristine resulted in gradual improvement and eventual complete remission which lasted for 2 years. When she relapsed, immediate improvement was observed with the combined treatment of plasmapheresis and vincristine. She has now been in complete remission again for 10 months. It is suggested that plasmapheresis plus vincristine should be used as the initial treatment for children with TTP.     

THROMBIN GENERATION IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA: Effect of Leukemia Immunophenotypic Subgroups

In this study, it is hypothesized that a planned increase in the dose of recombinant human erythropoietin (rh-EPO) can prevent transfusion in very low birth weight infants. Two different regimens of rh-EPO were administrated, one consisting in increasing dosage up to 5000 U/kg/wk, according to the individual reticulocytes response, and the second in a standard therapy of 1250 U/kg/wk. Fifty-one infants participated. Despite a significant higher reticulocytosis, the study was prematurely terminated due to the results of an interim analysis showing that transfusion was not avoided by increasing the rh-EPO. No significant differences were found between the two regimens concerning transfusion rate, volume transfused, gain in weight, and adverse effects. Progressive titration of rh-EPO to improve the biological response does not leave premature infants free of transfusion.     

Chronic relapsing thrombotic thrombocytopenic purpura: three case reports and update of the pathogenesis and therapeutic modalities

Chronic relapsing thrombotic thrombocytopenic purpura (CRTTP) is the rarest type of TTP, usually presenting in childhood. The aetiology is still not fully explained. The disorder is associated with the presence in plasma of unusually large von Willebrand factor (UlvWF) multimers that are especially prominent between episodes. CRTTP can be prevented by periodic plasma transfusions. We report three children with congenital CRTTP who have been successfully treated and maintained in prolonged remission by the prophylactic use of fresh frozen plasma without concurrent plasmapheresis. Two of the patients are sibs. Received: 12 August 1997 / Accepted in revised form: 8 December 1997     

儿童血栓性血小板减少性紫癜

血栓性血小板减少性紫癜（TTP）在儿童病例中甚为少见,但如未能及时诊断及施予治疗,其后果则极为严重。其最常见之5种病症为：血小板减少、微血管溶血性贫血、急性肾衰竭、发热及中枢神经系统症状。但临床病例中,并不一定会同时出现上述5种症状。故此医疗人员对此病必须有极高之警觉性。TTP之病理特征包括：外周血涂片可见裂体细胞,Coombs 试验阴性,血清乳酸脱氢酶增高及中度或重度血小板减少。TTP发病机理主因缺乏ADAMTS13,从而引发微血管溶血性贫血及血小板减少。TTP可概括分为家族性TTP（Upshaw Schulman 综合征）和继发性TTP。家族性TTP是由于先天性ADAMTS13缺乏所致,其急性治疗法为血浆置换,当病情稳定后,可输注新鲜冰冻血浆以防止病情复发。继发性TTP是指患者因体内产生抗体而导致ADAMTS13功能减退,主要治疗方法亦为血浆置换,最新之临床文献显示rituxiamb对此症亦颇有治疗价值。     

Thrombotic lesions of the tricuspid valve in a newborn: Surgical management

Summary Thrombotic lesions on the leaflets of the tricuspid valve in a premature infant with an anatomically normal heart are described. The diagnosis was made by two-dimensional and Doppler echocardiography. No etiologic explanation could be obtained from the history and clinical findings. The newborn had no infection, no antithrombin deficiency, and no indwelling catheter through either a peripheral, central or umbilical vein. The multiple masses were successfully removed by surgery under deep hypothermic circulatory arrest at 1 month of age. The child is well, without neurological deficit, and is developing normally.     

儿童继发性血栓性血小板减少性紫癜1例并文献复习

目的 提高对儿童不典型继发性血栓性PLT减少性紫癜（TTP）的认识。 方法 总结1例无神经系统受累的继发性TTP患儿的临床资料、实验室检查结果、ADAMTS13酶活性和Anti-ADAMTS13抗体检测结果,行系统文献检索并文献复习。 结果 男性患儿,12岁,急性起病,病初有发热,双下肢可见瘀点,PLT及Hb进行下降,血涂片可见破碎RBC,高胆红素血症,LDH明显升高,镜下血尿,肾功能正常,补体正常,考虑血栓性微血管病(TTP或非典型溶血尿毒综合征)。为进一步明确诊断, 行ADAMTS13酶活性检测2.3%（正常值40％~130%）,ADAMTS13抗体检测90 U·mL-1（正常值＜12 U·mL-1）,确诊继发性TTP,予血浆置换和激素治疗。4个月后患儿停用所有药物,目前停药6月无复发。系统检索中国知网、万方和PubMed数据库,共有14篇英文文献中40例继发性TTP进入本文分析,发病年龄（10.2±5.2）岁,男19例,女21例,发热36例（90%）,神经系统受累28例（70%）,肾脏受累18例（45%）,均有贫血和PLT降低。3例死亡,37例血浆置换+激素治疗,31例（83.8%）对血浆置换治疗即时反应好,1例因血浆过敏和1例血浆置换导管相关感染改为激素+利妥昔单抗治疗反应好,1例难治性继发性TTP加长春新碱（利妥昔单抗上市前）随访时复发,2例发生血浆置换依赖,加环孢素后治疗反应好,1例治疗反应不好,加长春新碱后治疗反应好,,4例失访（10.8%）,平均随访时间29月（3~72个月）,13例（39.4%）出现复发,9/13例加利妥昔单抗中仍有2例复发。 结论 贫血和PLT降低应怀疑TTP,需行ADAMTS13酶活性及其抗体的检测,有助于区别遗传性和获得性TTP;血浆置换+激素,或+利妥昔单抗是TTP的治疗组合选项。     

New strategies in diagnosis and treatment of thrombotic thrombocytopenic purpura: case report and review

The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults but also children have been described with this condition. The disorder may take a relapsing course, termed chronic relapsing TTP (CRTTP), which although very rare, may also begin in childhood. Deficiency of a recently identified enzyme, the von Willebrand factor (vWF)-cleaving protease, seems to play a major role in the development of TTP. We report on a 3-year-old boy with a dramatic but typical clinical course of CRTTP. At the time of diagnosis, neurological deficits and multiple cerebral infarctions had already occurred. In plasma, vWF-cleaving protease was completely absent, both during acute TTP and in remission. There was no protease inhibitor detected. Regular infusions of fresh frozen plasma were successfully given for replacement on a prophylactic basis. Conclusion Assay of von Willebrand factor-cleaving protease helps to diagnose a form of thrombotic thrombocytopenic purpura which may be managed by prophylactic treatment with fresh frozen plasma. Received: 13 April / Accepted: 4 May 1999     

肌酸激酶同工酶与血浆内皮素检测结合脑电图检查判断热性惊厥患儿脑损伤的程度及预后

目的探讨热性惊厥(FC)患儿血清脑型肌酸激酶同工酶(CK-BB)和血浆内皮素(ET)水平的变化及其两者结合脑电图(EEG)检查与脑损伤的关系。方法将2005-08—2006-12在潍坊医学院儿科就诊的52例FC患儿作为FC组,健康儿童28例作为正常对照组,分别进行血清CK-BB和血浆ET的测定及EEG检查,CK-BB采用比色法测定,ET采用放射免疫法测定。结果FC患儿血液中CK-BB和ET水平明显高于正常对照组(P均<0.01);单纯热惊厥(SFC)组CK-BB和ET的浓度与正常对照组比较差异无显著性(P>0.05);复杂热惊厥(CFC)组与正常对照组和SFC组比较差异均具有显著性(P均<0.01)。CFC组血清CK-BB与血浆ET呈正相关(r=0.652,P<0.01)。FC患儿惊厥发作后第1天EEG异常率为80.77%,其中SFC组78.12%,CFC组85.00%,差异无显著性(P>0.05);第14天为32.69%,SFC组仅18.75%,CFC组则55.00%,差异具有显著性(P<0.01)。结论CK-BB和ET水平与脑损伤的程度密切相关,CK-BB和ET含量越高脑损伤程度越严重。热性惊厥后及时检测CK-BB和ET,并结合脑电图检查对判断脑损伤程度及预后有重要价值。     

Eosinophilic gastrointestinal disorders and allergen immunotherapy: Lights and shadows

Allergic diseases, such as IgE-mediated food allergy, asthma, and allergic rhinitis, are relevant health problems worldwide and show an increasing prevalence. Therapies for food allergies are food avoidance and the prompt administration of intramuscular epinephrine in anaphylaxis occurring after accidental exposure. However, allergen immunotherapy (AIT) is being investigated as a new potential tool for treating severe food allergies. Effective oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) induce desensitization and restore immune tolerance to the causal allergen. While immediate side effects are well known, the long-term effects of food AIT are still underestimated. In this regard, eosinophilic gastrointestinal disorders (EGIDs), mainly eosinophilic esophagitis, have been reported as putative complications of OIT for food allergy and sublingual immunotherapy (SLIT) for allergic asthma and rhinitis. Fortunately, these complications are usually reversible and the patient recovers after AIT discontinuation. This review summarizes current knowledge on the possible causative link between eosinophilic gastrointestinal disorders and AIT, highlighting recent evidence and controversies.     

Childhood CNS inflammatory demyelinating diseases

CNS inflammatory demyelinating diseases (CIDD) are rare. At first presentation children are diagnosed with acute disseminated encephalomyelitis (ADEM) or a clinically isolated syndrome (CIS) such as transverse myelitis (TM) or optic neuritis (ON). Many of these disorders are monophasic, however a small number of children relapse and are diagnosed with multiple sclerosis (MS) or neuromyelitis optica (NMO). Paediatric onset Multiple Sclerosis (POMS) is a chronic inflammatory neurodegenerative demyelinating disease of the CNS that is usually relapsing-remitting at onset. There has been significant recent interest and progress in these disorders. Encephalopathy (behavioural change or altered consciousness) distinguishes ADEM from other demyelinating conditions. A high index of suspicion for CIDD is required in children presenting with neurological deficits, encephalopathy or status epilepticus. Several UK and international studies are underway to further our understanding of these diseases. There has been significant development of new treatments for MS and NMO. A national service for these rare disorders will enable better management of these well deserving patients. In this review we describe current understanding of the epidemiology, pathogenesis, clinical features, outcome and management of childhood CIDD.     

新生儿缺氧缺血性脑病血NSE与ET变化及其与高压氧治疗相关性的研究

目的 探讨肿瘤坏死因子-α(TNF-α)和降钙素基因相关肽(CGRP)在新生儿缺氧缺血性脑病(HIE)中的变化及临床意义。方法 采用放射免疫分析法对38例HIE患儿和18例健康足月新生儿血浆TNF-α与CGRP水平进行了同期动态观察。结果 HIE患儿急性期TNF-α,CGRP水平分别为(1.12±0.42) ng/ml,(88.92±23.16) ng/ml;恢复期分别为(0.61±0.18) ng/ml,(68.39±19.32) ng/ml;对照组分别为(0.54±0.15) ng/ml,(66.2±14.54) ng/ml。急性期血浆TNF-α和CGRP水平较恢复期显著增高(P<0.01),并明显高于同期对照组水平(P<0.01),恢复期与正常对照组无显著差异,急性期不同程度HIE与对照组TNF-α,CGRP水平比较,重度HIE组TNF-α,CGRP分别为(1.28±0.41) ng/ml,(118.12±30.25) ng/ml;中度HIE组分别为(0.95±0.3) ng/ml,(86.49±24.36) ng/ml,轻度HIE组分别为(0.63±0.19) ng/ml,(68.31±18.38) ng/ml,重度组明显高于对照组、轻度组及中度组,中度组高于对照组和轻度组,轻度组与对照组无显著性差异。急性期患儿血浆TNF-α与CGRP呈直线正相关关系(r=0.513,P<0.05)。结论 TNF-α和CGRP参与了新生儿HIE的发病过程。急性期TNF-α的增高可能是促发HIE脑损伤的一个重要因素,而CGRP增高在HIE中对脑损伤可能具有一定的保护作用。     

2日龄新生儿高胆红素血症合并血小板减少

患儿,女,生后2 d,因皮肤巩膜黄染半天入院。主要临床表现为持续严重的黄疸和血小板减少,最终确诊为先天性血小板减少性紫癜（TTP）。先后予光疗、输注新鲜冰冻血浆、红细胞、血小板及换血等治疗后,患儿病情好转。基因检测结果提示患儿ADAMTS13基因存在c.3650T > C (p.I1217T)纯合突变,其父母该位点均为杂合突变。先天性TTP是一种罕见的常染色体隐性遗传疾病,及时输注新鲜冰冻血浆可获得良好疗效。该病例为国内外首例报道该位点纯合突变所致的先天性TTP患儿。     

Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome

Aims

To evaluate whether procalcitonin (PCT) and C reactive protein (CRP) are able to discriminate between sepsis and systemic inflammatory response syndrome (SIRS) in critically ill children.

Methods

Prospective, observational study in a paediatric intensive care unit. Kinetics of PCT and CRP were studied in patients undergoing open heart surgery with cardiopulmonary bypass (CPB) (SIRS model; group I¹) and patients with confirmed bacterial sepsis (group II).

Results

In group I, PCT median concentration was 0.24 ng/ml (reference value <2.0 ng/ml). There was an increment of PCT concentrations which peaked immediately after CPB (median 0.58 ng/ml), then decreased to 0.47 ng/ml at 24 h; 0.33 ng/ml at 48 h, and 0.22 ng/ml at 72 h. CRP median concentrations remained high on POD1 (36.6 mg/l) and POD2 (13.0 mg/l). In group II, PCT concentrations were high at admission (median 9.15 ng/ml) and subsequently decreased in 11/14 patients who progressed favourably (median 0.31 ng/ml). CRP levels were high in only 11/14 patients at admission. CRP remained high in 13/14 patients at 24 h; in 12/14 at 48 h; and in 10/14 patients at 72 h. Median values were 95.0, 50.9, 86.0, and 20.3 mg/l, respectively. The area under the ROC curve was 0.99 for PCT and 0.54 for CRP. Cut off concentrations to differentiate SIRS from sepsis were >2 ng/ml for PCT and >79 mg/l for CRP.

Conclusion

PCT is able to differentiate between SIRS and sepsis while CRP is not. Moreover, unlike CRP, PCT concentrations varied with the evolution of sepsis.     

新生儿缺氧缺血性脑病血NSE与ET变化及其与高压氧治疗相关性的研究

目的探讨新生儿缺氧缺血性脑病血清神经元特异性烯醇酶（ＮＳＥ）与血浆内皮素（ＥＴ）变化及高压氧治疗的作用。方法高压氧治疗以纯氧加压,压力０．０５～０．０７ ＭＰ加压 ２０ ｍｉｎ．稳压 ２０ ｍｉｎ,减压 ２０ ｍｉｎ,共历时 １ｈ,每天一次,疗程５～１０ ｄ。ＮＳＥ活性测定采用酶联免疫分析法;ＥＴ活性测定采用放射免疫分析法。结果中度ＨＩＥ患儿血清ＮＳＥ与血浆ＥＴ浓度分别为（１４．７２±４ ２６）μｇ／Ｌ（７６．１±１９．２）ｎｇ／Ｌ;重度ＨＩＥ患儿血清ＮＳＥ与血浆ＥＴ浓度分别为（１５．６４±５．８２）μｇ／Ｌ,（８２．５±２１．６）ｎｇ／Ｌ;中、重度ＨＩＥ患儿血清ＮＳＥ与血浆ＥＴ浓度显著高于对照组（分别为１２．４７± ３．４９ μｇ／Ｌ, ５６．３２± １６．７ｎｇ／Ｌ）。轻度 ＨＩＥ患儿血清 ＮＳＥ（ １３．５８± ４．５７） μｇ／Ｌ,血浆ＥＴ（６２．４± １８．５） ｎｇ／Ｌ与对照组比较无显著差异。中、重度 ＨＩＥ患儿高压氧治疗后,血清 ＮＳＥ,血浆 ＥＴ降低幅度分别为（ １．９２± ０．４６）μｇ／Ｌ,（ １２．７２± ４． ３７）ｎｇ／Ｌ,明显大于常规治疗组（ Ｐ＜ ０．０５）。结论血清 ＮＳＥ和血浆 ＥＴ是ＨＩＥ早期诊断与疗效判     

Improved growth with growth hormone therapy in a child with glycogen storage disease Ib

In type Ib glycogen storage disease (GSD) growth is typically affected and short stature is a common feature. Reported use and effect of growth hormone (GH) therapy in children with GSD is limited. We report on the use of substitutive GH treatment in a poorly growing adolescent female with GSD type Ib. The patient's growth velocity increased from a baseline level of 2.5 cm/y to an average growth velocity during GH therapy of 8.7 cm/y. During GH therapy this patient did not demonstrate metabolic decompensation but increased levels of cholesterol and triglycerides were seen (A-1).

Conclusion: Patients with GSD may experience an improvement in growth response with GH treatment. Prior to GH therapy, treatment of hyperlipidemia associated with GSD should allow the therapy to be safely tolerated.