Severe protein S deficiency associated with heterozygous factor V Leiden mutation in a child with purpura fulminans

Homozygous or compound heterozygous protein S (PS) deficiency is very rare in the population; only 8 patients from 6 different families have been reported. On the other hand, the factor V Leiden (FVL) mutation is a frequent cause of inherited prothrombotic disorder. Here the authors report a case of patient with severe PS deficiency associated with the FVL mutation who has had purpura fulminans since the age of 10 days. She is the first child of a consanguineous marriage. Her father is double heterozygous for PS deficiency and FVL mutation and has recurrent thrombosis. This is the first case of severe PS deficiency combined with the FVL mutation. This suggests the need for complete evaluation of patients with purpura fulminans for thrombotic factors.     

Prothrombin G20210A mutation in Turkish children with thrombosis and the frequency of prothrombin C20209T

The prothrombin G20210A mutation has been described as the second most common genetic risk factor in thrombotic patients. Recently a new prothrombin gene variant namely prothrombin C20209T has also been found to be associated with thrombosis. In the present study the frequency of these two thrombin variants have been searched in two different groups. Group 1: A total of 377 children with thrombosis were analyzed during 7 years between January 1997 and 2004 and screened for prothrombin G20210A mutation. Twenty-four of 387 children (6.3%) with thrombosis were diagnosed as having PT G20210A mutation. The mean age of the patients was 6.1 years (median: 6 years, range: 4 months to 17 years, 15 male, 9 female). Six of 24 children were below 2 years of age (25%). Fifteen of 24 children (62.5%) had arterial thrombosis, most of whom (93.3%) had cerebral infarct. Group 2: The prothrombin C20209T variant has been analyzed in 200 thrombotic patients and in 200 healthy subjects. None of the thrombotic patients and healthy individuals carried the prothrombin C20209T variant. In conclusion, arterial thrombosis as the cerebral infarct is the most prominent type of thrombosis in children with prothrombin G20210A mutation. It seems that the prothrombin C20209T variant is not an important risk factor for the population studied.     

Varicella and thrombotic complications associated with transient protein C and protein S deficiencies in children

We report six cases of protein S deficiency secondary to varicella. Five cases were complicated by thrombotic and vascular events, namely purpura fulminans and necrotic vasculitis, deep vein thrombosis and stroke. Two cases were associated with protein C deficiency and one case revealed a heterozygous factor XII deficiency. The underlying mechanism of this acquired protein S deficiency is unclear but could be related to a direct effect of zoster virus.     

A rare association between group A Streptococcus purpura fulminans and diffuse alveolar hemorrhage in a young girl: A case report

We report the case of a 7-year-old girl with septic shock and coagulopathy associated with purpura fulminans (PF) and diffuse alveolar hemorrhage (DAH) due to group A Streptococcus (GAS) infection identified with 16S ribosomal RNA analysis performed on the skin biopsy. GAS infection with PF associated with DAH is rare in healthy young children but pediatricians should be aware of this condition because of the poor prognosis. The initial treatment for circulatory failure and severe disseminated intravascular coagulation as well as the prompt initiation of antibiotic treatment may be crucial for the outcomes of S. pyogenes PF.     

口服抗凝剂治疗以新生儿暴发性紫癜或颅内出血为首发表现的遗传性复合杂合突变的重度蛋白C缺乏症2例病例报告并文献复习

背景：既往国内报道的重度遗传性蛋白C缺乏症(PCD)患儿大多放弃救治而死亡。 目的：探索口服抗凝剂对重度PCD患儿的长期救治效果。 设计：病例报告。 方法：报道并分析2例新生儿期起病的遗传性复合杂合突变的重度PCD患儿的诊断、治疗及预后,检索PubMed、中国知网和万方数据库,行文献复习。 主要结局指标：血栓或出血缓解。 结果：1例首发表现为新生儿暴发性紫癜（PF）;1例因存在继发性慢性DIC,以新生儿颅内出血、肺出血为首发表现。2例经基因测序均明确蛋白C(PROC)基因复合杂合突变。每日应用新鲜冷冻血浆及低分子肝素抗凝获得初步缓解后,分别序贯口服维生素K拮抗剂华法林或直接口服抗凝剂利伐沙班作为长期治疗,预防血栓及出血事件,随访3~6年,2例均存活至今,生存质量尚好,且无明显不良反应。 结论：重度遗传性PCD可以新生儿PF、颅内出血和肺出血为首发表现,应改变观念积极救治;华法林和利伐沙班等口服抗凝剂可以作为长期维持治疗时安全有效的选择,改善预后。     

Purpura fulminans as a sequel to erythema nodosum in a child with homozygous Leiden mutation and acquired protein S deficiency

A 6-y-old boy presented with generalized, bruise-like swelling of both legs. Three weeks later, he developed purpura fulminans in one of the affected feet. Histology of the leg swelling was in accordance with erythema nodosum. The boy proved to be homozygous for the Factor V Leiden mutation and to have acquired protein S deficiency. He recovered, with partial loss of two toes. CONCLUSION: In contrast to what is often stated, erythema nodosum is not always a benign condition. On the basis of this report, we suggest that if extensive erythema nodosum develops in an individual without any known thrombophilic disorder, investigations with respect to the latter should be performed.     

Coexistence of acquired protein S and protein C deficiency and the Arg506Gln mutation in factor Va in a child with severe thromboembolic disease

An 11-y-old girl who presented with cellulitis and clinical signs of deep vein thrombosis (DVT) is reported here. She developed staphylococcal sepsis, recurrent septic emboli and a large vegetation on the tricuspid valve. The patient was found to be heterozygous for the Arg506Gln mutation in factor Va and had low levels of protein C and protein S during the sepsis. The coexistence of the two thrombophilic states may explain the severe thromboembolic manifestations.     

上海市单中心儿童幽门螺杆菌不同治疗方案根除率及其耐药率的横断面调查

目的 考察上海市儿童幽门螺杆菌常用治疗方案的根除率和幽门螺杆菌的耐药率。方法 回顾性收集复旦大学附属儿科医院(我院)2014年1月1日至2017年9月19日门诊内镜诊断幽门螺杆菌感染、完成1个治疗方案(2周)且随访幽门螺杆菌根除情况的病例,从我院电子病历系统中截取性别、诊断年龄、主诉、内镜表现、尿素酶试验(RUT)结果、病理检查、胃黏膜培养及药敏结果、治疗方案和疗程等。完成1个治疗方案1个月后来我院行尿素呼气试验(UBT)或胃镜RUT检测,其中1项阴性判断为幽门螺杆菌根除。结果 1 558例确诊幽门螺杆菌感染患儿进入本文分析,平均年龄(8.5±3.1)岁,男性56.5%,腹部不适主诉占74.6%,非溃疡病变占85.0%。均为经验性治疗且均完成了标准治疗时间。一线治疗+补救治疗根除率56.7%(883/1 558),其中一线治疗和补救治疗根除率分别为56.4%(751/1 331)和58.1%(132/227),差异无统计学意义。一线治疗中奥美拉唑(OME)+克拉霉素(CLA)+阿莫西林(AMO)/阿莫西林-克拉维酸钾(AMOc)、OME+CLA+甲硝唑(MET)和其他治疗方案根除率分别为57.9%(659/1 139)、31.8%(34/107)和68.2%(58/85),OME+CLA+MET治疗方案根除率低于其他治疗方案;补救治疗中,铋+OME+CLA+AMO/AMOc、铋+OME+CLA+MET和其他治疗方案根除率分别为57.6%(87/151)、52.3%(23/44)和68.8%(22/32), 两两比较差异无统计学意义。幽门螺杆菌培养阳性579株菌株中,CLA、MET和AMO的耐药率分别为31.8%、45.1%和1.4%;CLA和MET同时耐药率为23.0%。根除(一线+补救)治疗失败和治疗成功分别为259和320例,根除治疗失败病例的CLA耐药率(44.0% vs 21.9%)、MET耐药率(52.5% vs 39.1%)和CLA+MET同时耐药率(32.4% vs 15.3%)均显著高于根除治疗成功病例,差异均有统计学意义。一线和补救治疗分别为475和104例,CLA、MET和CLA+MET同时耐药率分别为(29.5% vs 42.3%)、(42.7% vs 55.8%)和(20.4% vs 34.6%),差异均有统计学意义。结论 因为CLA、MET高耐药等原因,儿童标准三联疗法的根除率只有56.4%,可能不适合在临床上作为幽门螺杆菌的一线治疗方案继续使用。但改善患儿服药依从性、提高药物剂量(如质子泵抑制剂和AMO)等是否可以提高标准三联疗法的根除率还有待进一步研究。