遗传性血小板无力症的发病机制及产前诊断

目的探讨血小板无力症(GT)的基因测序与产前诊断。方法采集1例表型GT患儿、父母及1例正常对照者的静脉血,患儿母亲腹中孕23周胎儿的脐带血和羊水,及其出生2 d时的静脉血。检测患儿、患儿父母、胎儿脐血及正常对照者的血凝常规和血小板聚集试验;流式细胞仪检测血小板膜糖蛋白(GP)Ⅱb和GPⅢa的表达;微卫星技术确定胎儿脐血是否被母体细胞污染;PCR技术扩增患儿及其父母,以及胎儿及出生2 d静脉血GPⅡb、GPⅢa所有外显子以及外显子和内含子交界区,扩增产物直接测序。结果二磷酸腺苷(ADP)不能诱导患儿的血小板发生聚集,胎儿脐血中ADP诱导的血小板最大聚集率约为正常人一半,患儿父母和胎儿出生2 d的ADP诱导的血小板最大聚集率与正常血小板聚集率相当。患儿血小板膜表面GPⅡb、GPⅢa的的平均荧光强度(Mn X)分别约为正常对照的10%及0,而患儿父母、胎儿脐血和胎儿出生2 d的Mn X分别为正常对照的90%以上和30%~50%。羊水胎儿脱落细胞和脐血DNA微卫星分析证实胎儿羊水、脐血未被母体细胞污染;基因分析结果显示,患儿GPⅢa 6号外显子A38293→C和9号外显子G42186→A的杂合突变,导致GPⅢa His281→Tyr和Cys400→Pro氨基酸的杂合改变。这两个突变分别来源于父亲和母亲。羊水胎儿脱落细胞、脐血或出生2 d静脉血中只有1个GPⅢa9号外显子G42186→A的杂合突变。结论 GT患儿GPⅢa的基因为双重杂合突变;胎儿出生后确证为GPⅢa基因杂合突变。     

血小板无力症患者出血机制的初探

目的探讨血小板无力症(glanzmann’s thrombasthenia,GT)患者血小板聚集功能异常的可能机制。方法采用流式细胞仪检测血小板糖蛋白Ⅱb(GPⅡb,CD41)/Ⅲa(GPⅢa,CD61)含量,并通过血小板聚集试验、血小板黏附试验、血块收缩试验对血小板功能的检测。结果GT患者血小板糖蛋白Ⅱb(GPⅡb,CD41)/Ⅲa(GPⅢa,CD61)含量明显低于正常,血小板聚集试验、血小板粘附试验、血块收缩试验明显较正常低下,出血时间较正常明显延长。结论血小板GPⅡb/Ⅲa量的减少及功能障碍是导致血小板无力原因,可能机制与其相关基因突变有关。     

流式细胞术快速确诊小儿血小板无力症

血小板无力症(glanzmann’s thrombasthenia,GT)是一种罕见的常染色体隐性遗传性疾病,其发病机理是由于血小板膜纤维蛋白原受体GPⅡb／Ⅲa糖蛋白缺乏,使血小板不能聚集所致。临床主要表现为反复出血。血小板糖蛋白GPⅡb／Ⅲa归属于CD41a／CD61,采用抗人CD41a／CD61和流式细胞术(FCM)能从分子水平对GT作出明确诊断。最近本     

小儿原发性血小板增多症4例临床及实验室分析

目的探讨小儿原发性血小板增多症(ET)的临床、实验室特征。方法诊断依PVSB标准;行血常规、骨髓细胞形态学、凝血四象、血小板功能等检查。确诊后给予抗凝、活血或马利兰治疗。结果4例患儿中以出血症状诊断2例、血栓症状诊断2例;脾肿大3例;外周血血小板(Plt)724~1028×109/L,易见Plt聚集成堆,可见巨大Plt、畸形Plt;骨髓象巨核细胞明显增多,分类以产板型为主;3例APTT延长,血小板粘附率、聚集功能降低。治疗后症状均缓解,随访至今无恶性转化。结论ET患儿具典型的临床和实验室特征,临床应予以重视,以防误诊。     

小儿血小板无力症22例临床分析

血上板无力症（glanzmann thrombsathenia,GT) 为遗传性血小板功能缺陷中最为常见的疾病,是血小板膜糖蛋白ＩＩb/ＩＩIa/IIIa)数量减少或结构异常所致的出血性疾病^[1]。下面根据１９８６年后的标准诊断总结我科１９８３－１９９９年门诊及病房共２２例ＧＴ资料^[2]。     

遗传性血小板无力症发病机制及治疗进展

遗传性血小板无力症是一种遗传性血小板功能障碍性疾病,由于血小板膜糖蛋白GPⅡb/Ⅲa数量或结构异常,导致血小板对多种诱聚剂反应不良.临床表现为自幼反复发生的自发性出血,且常伴终生.本病属罕见遗传性疾病,尚无统一的根治性治疗措施.文章对遗传性血小板无力症的发病机制及治疗进展作一综述.     

NICU中血小板减少症的临床分析

目的　 探讨 NICU中血小板减少症的临床特点。方法　对 NICU中 42 9例本病患儿的临床资料进行回顾性分析。结果 　 NICU中血小板减少症发生率为 31.45 % ,主要致病原因为感染 (占 70 .16 % ) ,其次包括免疫因素 ( 2 .10 % )、先天遗传因素等 ,仍有约 2 5 .6 4%原因不明。 5 8.79%的患儿临床有出血表现 ,对重症患儿输注血小板治疗有效 ,不同病因所致者预后有一定差异。 结论 　N ICU中血小板减少症发生率高 ,病因复杂 ,应动态监测、及时处理 ,防严重并发症和后遗症发生     

小儿原发性血小板增多症4例临床及实验室分析

目的 探讨小儿原发性血小板增多症（ET）的临床、实验室特征.方法 诊断依PVSB标准;行血常规、骨髓细胞形态学、凝血四象、血小板功能等检查.确诊后给予抗凝、活血或马利兰治疗.结果 4例患儿中以出血症状诊断2例、血栓症状诊断2例;脾肿大3例;外周血血小板（Plt）724～1028×10^9/L,易见Plt聚集成堆,可见巨大Plt、畸形Plt;骨髓象巨核细胞明显增多,分类以产板型为主;3例APTT延长,血小板粘附率、聚集功能降低.治疗后症状均缓解,随访至今无恶性转化.结论 ET患儿具典型的临床和实验室特征,临床应予以重视,以防误诊.     

免疫性血小板减少症合并心肌损伤患儿临床分析

目的 探讨合并心肌损伤的免疫性血小板减少症(ITP)患儿的临床特点.方法 回顾分析2018年12月至2020年4月收治的新诊断ITP患儿的临床资料,根据是否合并心肌损伤将患儿分为非心肌损伤组和心肌损伤组,并分析两组的临床特点、实验室检查以及转归情况.结果 新诊断ITP患儿360例,男240例、女120例,中位年龄3.0...     

极低出生体重儿早发血小板减少症多因素相关分析

目的探讨极低出生体重儿早发血小板减少症的相关因素。方法选择2011—2013年我院NICU收治的极低出生体重儿进行回顾性研究。根据生后72 h内有无血小板减少症分为早发血小板减少症组和无早发血小板减少症组,对两组患儿临床情况进行比较。结果108例研究对象入选,发生早发血小板减少症45例(41.7%),患儿血小板计数在中位数8天恢复正常。男婴(OR=6.036)、早发感染(OR=8.358)及孕母患妊娠期高血压疾病(OR=5.990)与极低出生体重儿早发血小板减少症相关(P<0.05),胎龄、出生体重、胎膜早破、窒息、产前应用地塞米松、呼吸窘迫综合征等对极低出生体重儿早发血小板减少症无明显影响。结论早发血小板减少症是极低出生体重儿的常见合并症,男婴、早发感染及孕母患妊娠期高血压疾病是极低出生体重儿早发血小板减少症的危险因素。     

CLINICAL AND PATHOLOGICAL ASPECTS OF CENTRAL NERVOUS SYSTEM INVOLVEMENT IN THE HAEMOLYTIC URAEMIC SYNDROME

Major clinical neurological features were seen in 13 of 25 consecutive patients with the haemolytic uraemic syndrome (HUS). Convulsions were present in 11 of these patients Hemiparesis, aphasia, coma, and decerebrate spasms were other manifestations and these were associated with a mortality of 90% compared with an overall mortality of 45%. Two case histories are given in which neurological involvement was the presenting and predominant clinical feature. Neuropathological examination showed hypoxic and/or ischaemic lesions and cerebral oedema as the most frequent changes, but did not reveal distinctive vascular lesions similar to those seen in the kidney. The diagnosis of HUS should be considered in severe acute and subacute encephalopathies of obscure origin in childhood.     

Diagnostic value of serum gamma-glutamyl transpeptidase activity in liver diseases in children.

The clinical usefulness of serum gamma-glutamyl transpeptidase (gamma GT) assay for the diagnosis of liver disease in children was assessed retrospectively in 398 children investigated from 1981 to 1986, in whom diagnosis was ascertained according to currently accepted criteria including liver histology in each case. Serum gamma GT activity was within normal limits in 10 controls, in 19 children with portal vein obstruction, and in 10 of 12 children with congenital hepatic fibrosis. Serum gamma GT was raised in all children with biliary atresia, sclerosing cholangitis, paucity of interlobular bile ducts, and alpha 1-antitrypsin deficiency with jaundice. Serum gamma GT was normal in spite of patent clinical signs of cholestasis in 3 patients with benign recurrent intrahepatic cholestasis, 1 infant with post-hemolytic neonatal cholestasis, and in 22 of 28 patients with progressive idiopathic cholestasis akin to Byler disease. In the latter group, children with raised serum gamma GT displayed extensive portal fibrosis and bile duct proliferation on liver histology, while this was not a prominent feature in children with normal serum gamma GT. These results indicate (a) the value and limits of the assay for serum gamma GT activity in children with liver disease, (b) that raised serum gamma GT may be considered a fairly reliable index of bile duct damage, and (c) that serum gamma GT may prove a useful tool in separating two forms of progressive idiopathic cholestasis, with or without bile duct involvement.     

Is bone marrow examination justified in idiopathic thrombocytopenic purpura?

Bone marrow examination is widely accepted among pediatric hematologists as a mandatory investigation in childhood idiopathic thrombocytopenic purpura (ITP). The aim of this procedure is to confirm the presence of megakaryocytes and to exclude other conditions, such as leukemia and aplastic anemia. To assess the need for bone marrow examination, we reviewed the charts of 127 children with presumed ITP and found that bone marrow examination led to a different diagnosis in five (3.9%) of them. All five patients had presented with clinical and/or laboratory features atypical of acute ITP; none had leukemia. The initial clinical and laboratory findings of 50 patients with aplastic anemia also were reviewed; all had features atypical of acute ITP. Proper history and physical examination as well as a complete blood cell count are reliable means of recognizing patients with typical vs atypical features of ITP. Bone marrow aspiration could be limited safely to those patients with atypical features of ITP or to patients being treated with corticosteroids.     

Manometric evaluation of the intrathoracic stomach after gastric transposition in children

Gastric transposition (GT) is one of the options for the esophageal replacement in children with esophageal atresia with or without tracheoesophageal fistula (EATEF). To date, no manometric studies have been conducted on the intrathoracic stomach after GT in EATEF patients; hence, this study was designed. Babies (n=18) of EATEF who underwent esophageal replacement by GT were studied and manometry was correlated with the clinical outcome, age at surgery, and route of GT. The mean age at evaluation was 30.5 months (range 4–84 months). These cases were sub-stratified into group I (GT during neonatal period) and group II (GT during post-neonatal period). Mean age at surgery was 6 days and 7.8 months in groups I and II, respectively. There was no propulsive antegrade propagated peristaltic waves in any of the patients. Mean resting pressure and mean peak pressures were 19.5 and 50.4 mm Hg in groups I and II, respectively. Mass contractions to liquid swallow was noted in 77 and 55% of patients in groups I and II, respectively. There was no significant difference in the pressure parameters or appearance of mass contractions between group-I and group-II patients. Similarly, there was no significant difference in pressure parameters or appearance of mass contractions between the children who had transhiatal vs retrosternal GT. It needs to be determined whether the mass contractions noted in GT ever progress to a coordinated propulsive rhythmic contractions and whether this has a final bearing on the long-term functional outcome of GT patients.     

A polymorphism in plasma platelet-activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in Kawasaki disease

OBJECTIVE: To investigate whether reduced levels of plasma platelet-activating factor acetylhydrolase (PAF-AH) as a result of a genetic polymorphism are involved in the pathogenesis of Kawasaki disease (KD). STUDY DESIGN: The frequency of a V279F polymorphism (G/T transversion) in the PAF-AH gene was quantified in 76 Japanese children with KD and 112 healthy Japanese adults using the allele-specific polymerase chain reaction (PCR). Associations between genotype, clinical features, and resistance to intravenous immunoglobulin (IVIG) were investigated in the patients with KD. Plasma PAF-AH activity was measured by using [3H]-acetyl-PAF. RESULTS: There were no significant differences in genotype frequency between patients and controls (P = .51). Compared with the GG (normal genotype) group, significantly more patients in the GT (heterozygous) +TT (homozygous deficient) group required additional IVIG (52% vs 14%, P = .001). The duration of fever and maximum serum C-reactive protein (CRP) levels also were significantly increased in the GT+TT group (P = .012 and .036, respectively), whereas plasma PAF-AH activity was significantly lower (P <.0001). CONCLUSION: We conclude that the V279F polymorphism in the plasma PAF-AH gene and consequent enzymatic deficiency is one of the factors for IVIG nonresponse in Japanese patients with acute KD.     

Granulocyte transfusion: Stimulation of low dose granulocyte colony-stimulating factor in donors for leukapheresis

In order to assess the clinical utility of granulocyte transfusions (GT), the stimulating effects of donor granulopoiesis for GT therapy were examined using either low dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) or dexamethasone (DEX). The increment of leukocytes, polymorphonuclear cells (PMN) and monocytes in the subjects stimulated with rhG-CSF (0.7 μg/kg SC) surpassed each increment in those with DEX alone (1 mg PO). The lymphocyte counts after DEX stimulation decreased in contrast to those after G-CSF stimulation. This dose of G-CSF did not enhance the priming effects on the superoxide release from PMN. The serum levels of lysozyme, but not of lactate dehydrogenase, in G-CSF stimulated donors were higher than those in DEX-treated donors. The serum macrophage/monocyte-colony stimulating factor (M-CSF) levels in DEX stimulation were lower than in either G-CSF stimulation or no stimulation. The net yield of the PMN in GT on G-CSF stimulation was practically larger than that on DEX stimulation. One of the two patients who received GT collected by DEX stimulation died of aspergillosis. Two of the five patients who received PMN mobilized by G-CSF died of fungal infections or necrotizing fasciitis, although two of the remaining patients overcame severe bacterial infections. These results suggest that low dose G-CSF effectively and safely mobilizes a sufficient quantity of PMN from GT-donors without excessive superoxide generation from the transfused cells. This low dose G-CSF stimulation may be substituted for conventional DEX stimulation for GT.     

45,X/46,X,dic(Y)-Mosaicism in the newborn

We report on a phenotypically male newborn with 45,X/46,X,dic(Y)-mosaicism. Right-sided inguinal hernia was surgically corrected. Histological examination of the tissue revealed an ambiguously differentiated gonad on this side. The clinical, cytogenetic, and histological results are described and the prognosis and clinical management of these patients are discussed.     

Cold agglutinin syndrome after rubella infection]

Cold agglutinins are antibodies against erytrocyte membrane antigens, and are produced primarily or secondarily. We report on the case of a 5 year old girl who developed cold agglutinin disease 3 days after an attack of German measles. Following exposure to cold, appeared blue-red cutaneous manifestations of the fingers, hands cheeks and nose. The clinical manifestations cleared up without any specific therapy. The occurrence of cold agglutinins after German measles is rare. The case report is discussed within the context of reports in the literature.     

Critical analysis of caregiver perceptions regarding gastrostomy tube placement

Background:  Gastrostomy tubes (GT) are often required to safely provide nutrition in children with feeding disorders and aspiration risk. The need for a GT brings with it known risks, complications, and benefits, but caregivers may have unspoken concerns and expectations. The present study was done to assess caregiver concerns, expectations, and satisfaction with GT placement in children.
Methods:  A two-part retrospective and prospective study was conducted to assess caregiver concerns and expectations related to GT placement, to determine which concerns and expectations came to fruition, and to rate overall satisfaction with the GT. Questionnaires were used to collect data before and after GT placement. A visual analog scale (VAS) score was used to determine degree of concern and satisfaction.
Results:  Sixty-four children (19 retrospective, 45 prospective) completed the study. Concern score by VAS was evenly distributed with a mean value of 47.4 ± 31.8. Concerns were realized in 25%; expectations were met in 93%. Feeding time decreased following GT placement. Satisfaction was reported as satisfied (23.6%), pleased (16.4%), or very pleased (60.0%).
Conclusions:  Despite pre-placement concerns, most caregivers reported being pleased with the GT following placement. Concerns that occurred were of minor medical significance. Most expectations were met, in particular improved nutrition. The present study provides insight into caregiver concerns and expectations, and which are likely to occur. This information can be useful when counseling caregivers of children requiring GT.     

Encephalopathy and fatty metamorphosis of the liver associated with cold-agglutinin autoimmune hemolytic anemia.

Three patients with encephalopathy clinically indistinguishable from Reye syndrome but associated with elevated cold-agglutinin titers and antiglobulin-I autoimmune hemolytic anemia are reported. The patients were treated with exchange transfusions, dexamethasone, controlled hyperventilation, and intracranial pressure monitoring. Liver biopsy specimens in two of the three patients showed fatty infiltration of the hepatocytes, but the light microscopic and electron microscopic appearance of the liver was not typical for Reye syndrome. These patients are reported to alert physicians to a metabolic encephalopathy in children which mimics Reye syndrome, but is distinctly different in clinical course and complicated by cold agglutinins and an autoimmune hemolytic anemia.