High levels of FVIII and FIX in a pediatric patient with retinal artery occlusion

A 13-year-old female patient with the diagnosis of retinal artery occlusion was evaluated for thrombophilia. The data revealed high FVIII and FIX levels. The patient had familial clustering. The data indicate that elevated FVIII and FIX could be a risk factor for thrombosis.     

Antibody neutralizing material of factor VII during the first weeks of life

In a study on 66 newborns and infants, factor VII activity and factor VII related antigen were investigated on 110 occasions. A normal range was calculated by testing plasma from 12 healthy male volunteers at various dilutions. Most of the values in the newborns and infants fell within this range but 18.2% of the factor VII proteins showed a significantly different specific activity.In honour of Prof. Dr. Goetze (Director of the Institute of Pathophysiology of the University Jena) on the occasion of his 65th birthday     

HIGH LEVELS OF FVIII AND FIX IN A PEDIATRIC PATIENT WITH RETINAL ARTERY OCCLUSION

A 13-year-old female patient with the diagnosis of retinal artery occlusion was evaluated for thrombophilia. The data revealed high FVIII and FIX levels. The patient had familial clustering. The data indicate that elevated FVIII and FIX could be a risk factor for thrombosis.     

Congenital deficiency of factor VII

A case of congenital factor VII deficiency in a five-year-old child is reported. The patient, born of a non-consanguineous marriage, presented with repeated bouts of epistaxis since childhood. The prothrombin time (PT) was markedly prolonged with a normal bleeding time (BT), partial thromboplastin time with Kaolin (PTTK) and platelet count. The patient has been on follow up for the last four years and is doing apparently well.     

Diagnostic Symptoms of Severe and Moderate Haemophilia A and B A Survey of 140 Cases

ABSTRACT. With a view to the characterisation of presenting symtoms, a survey was made of 140 boys diagnosed as having haemophilia A or B, severe or moderate form, in Sweden during the years 1960–1987. Mean age at diagnosis was nine months for the severe cases and 22 months for the moderate cases. Although the heredity was known in 59/140 cases, 35 had had bleeding episodes before diagnosis had been established, thus emphasising the importance of genetic information and carrier identification in haemophilia families. Of the presenting symptoms, subcutaneous bleedings constituted 41% while joint and muscle bleedings were uncommon; 16% were bleedings in conjunction with puncture of vessels, injections or surgery. Fourteen percent had anaemin and received blood-transfusion at diagnosis; 9% were diagnosed post-neonatally but 20% had shown abnormal bleeding tendency already in the neonatal period; seven boys (5%) had intracranial haemorrhages, five of them neonatally. A thorough family history and an extensive investigation of bleedings in the neonatal period should make early diagnosis possible.     

Serum levels of C3 and Factors I and B in minimal change disease

Abstract Background: Relapses are an important problem in minimal change disease, which accounts for most of the cases of childhood nephrotic syndrome. Because of defects in the humoral immune system, patients are predisposed to infection in nephrotic syndrome and infection is the most important complication that determines mortality and morbidity.
Methods: In this study, serum levels of Factors I and B and C3 were studied to evaluate the relationships between nephrotic syndrome and infection in 17 children with nephrotic syndrome (24–96 months of age) and 10 healthy children (27–84 months of age).
Results: Serum levels of Factors I and B were found to be lowered in the active disease group compared with the control group. These values were lowest for the infection group. Although it was observed that these values increased with steroid treatment, they did not reach normal levels. The parameters in remission were not different from the parameters in the control subjects. The serum level of C3 was found to be high during the active disease state and returned to normal levels during remission.
Conclusions: The patients with active minimal change disease had infections such as peritonitis, septicemia and urinary tract infection because of low concentrations of Factors I and B in their sera.     

Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death

Objective

To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death.

Study design

In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption — PVD). In the remnant 79 cases, no cause of death or associated condition was found.Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed.

Results

Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR = 3.2, 95% CI: 1.3–8.3, p = 0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR = 8.9, 95%CI 1.2–70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR = 3.8, 95% CI: 1.3–13.5).

Conclusion

These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.     

Intracranial haemorrhage due to factor V deficiency

Factor V deficiency is a rare coagulation disorder which is inherited autosomal recessively. Factor V deficiency should be considered in infants with bleeding disorders and prolonged prothrombin and activated partial thromboplastin times if bleeding continues in spite of vitamin K injection. In this article, the case of an infant with an intracranial haemorrhage due to congenital factor V deficiency is reported.     

FACTOR VIII ACTIVITY AND ANTIGEN IN SICK NEWBORNS WITH PATHOLOGICAL PROTEOLYSIS IN BLOOD

ABSTRACT. Factor VIII clotting activity (VII:C) and factor VIII related antigen (VIII:R:AG) were determined in 12 sick newborn infants with pathological proteolysis in their circulation. A marked discrepancy was noted between VIII:R:AG and VIII:C, the ratio in sick infants being, on average, 2: 1, while no discrepancy was seen in healthy newborns. The finding in the sick infants resembled a low grade plasminogen activation, which was studied experimentally. It is concluded that demonstration of a marked discrepancy between VIII: R: AC, and VIII:C is a useful indication of pathological proteolysis in sick newborns.     

Congenital factor VII deficiency

A 1 1/2-month-old baby with seizures, lethargy and refusal of feeds was diagnosed to have intracranial hemorrhage due to factor VII deficiency. MRI also demonstrated the unusual presence of a hemorrhagic infarct. The case underscores the importance of carrying out neuroimaging and appropriate hematological studies even in the absence of obvious external bleeding. Hypothesis for increased propensity for intra-cranial hemorrhage is discussed.     

RNA干扰对神经母细胞瘤细胞VEGFA的mRNA表达的影响

目的 构建表达VEGF-A的短发夹RNA真核表达载体,并通过其介导的RNA干扰作用,研究对人神经母细胞瘤细胞株IGR-N-91细胞中VEGF-A的mRNA表达的影响.方法 根据VEGF-A的cDNA序列合成两对寡核苷酸片段,退火后分别插入真核表达载体组成重组质粒.对重组质粒进行PCR、测序鉴定验证后,经Western Blot筛选RNA干扰效果最佳的质粒,然后将该质粒转染人神经母细胞瘤细胞株IGR-N-91.转染48 h后提取总RNA,逆转录为CDNA,经RT-PCR半定量检测VEGF-A mRNA的表达水平.结果 成功构建含有VEGF-A的RNA干扰片段真核表达载体,经Western Blot筛选后分别得到RNA干扰效果最佳的片段.RT-PCR结果表明质粒转染人神经母细胞瘤后VEGF-A的mRNA的表达升高.结论 成功构建含有人VEGF-A的RNA干扰片段的真核表达载体,该重组质粒转染人神经母细胞瘤IGR-N-91细胞后VEGF-A的mRNA表达升高.     

CLINICAL MANIFESTATIONS IN THROMBOTIC CHILDREN WITH FACTOR V LEIDEN MUTATION

Sixty-three children with thrombosis were screened for factor V Leiden (FVL) and the mutation was found in 20 patients, 5 of whom were homozygous for FVL. The clinical features of 15 heterozygous and 5 homozygous patients with factor V Leiden mutation were analyzed. Additional risk factors were found in 19 of these 20 patients (95%) with FVL mutation. The most frequent predisposing exogenous factor was infection. The majority of children with FVL mutation had had several associated disorders prior to their vascular occlusion, such as homocystinuria, Behcet's disease, collagen tissue disorders, and hypereosinophilia. Homozygous mutation in two children led to amputation of legs due to purpura fulminans. Cerebral thrombosis as cerebral infarct was frequent among children with FVL mutation.     

The clinical relevance of factor VIII: C and factor VII R: Ag determination in newborns

Higher levels of factor VIII: C and factor VIII R: Ag were found in healthy newborns (n=60) as compared to adults. This could be explained as a stress reaction due to birth and the adaptation to extrauterine life. A further stress factor is disease. The highest values for factor VIII R: Ag were found in ill (n=32) and in severely ill newborns (n=21). The large ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in healthy newborns can be explained by an increased turnover of coagulation factors. Diseases in the newborn period lead to an increase of this process, resulting in even larger ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in ill and extremely ill newborns. Consumption of factor VIII: C with a low ratio of factor VIII: C/VIII R: Ag predominates in extremely ill newborns. The ratio of factor VIII: C/VIII R: Ag is more valuable than factor VIII: C for diagnosis of DIC in newborns.A diagnosis of hemophilia and von Willebrand's disease cannot be established with certainty in severely ill newborns. Stress and DIC may influence the characteristic changes of laboratory parameters.Supported by Wissenschaftsministerium des Landes Nordrhein-Westfalen     

新生儿血友病A 11例病例系列报告

目的 探讨新生儿血友病A的临床表现、诊治及预后。方法 对复旦大学附属儿科医院2016年2月1日至2019年6月30日收治的11例新生儿血友病A临床资料进行回顾性分析。结果 11例新生儿血友病患儿均为男性,3例有明确血友病家族史。2例无出血表现,2例仅表现为皮肤瘀点瘀斑,7例有出血表现。出血部位包括硬膜下、颅内、皮下、消化道。11例活化部分凝血酶时间(APTT)均延长,均为凝血因子Ⅷ缺乏,中间型9例,重型和轻型各1例。5例行基因检测者证实FⅧ基因突变,缺失2例,点突变3例。血友病A确诊后予静脉输注Ⅷ因子。随访至2019年6月9~10日,1例失访,4例无出血表现,1例有踝关节自发出血表现,5例表现为外伤后皮肤瘀点/皮下血肿。结论 新生儿期多次凝血功能异常,以APTT延长为主,特别是延长＞3倍者有或无出血表现均应考虑血友病可能,应行凝血因子活性水平测定及基因检测及早确诊,早期诊断和预防性输注凝血因子可改善预后。     

The influence of perinatal risk factors on the incidence of atypical coagulation factor VII during the first days of life

The correlation between the appearance of functionally-atypical factor VII and perinatal complications was investigated in 66 newborn infants. The presence of an abnormal clotting factor was assumed if the ratio between clotting activity and antigen-related factor VII material exceeded the normal range for adult plasma. The newborns were divided into a risk group of infants threatened by adverse conditions of labour or post-natal adaptation, and a control group of newborns without perinatal complications. The findings were as follows:The incidence of atypical factor VII was significantly higher in the risk group. There was no difference between prenatal and postnatal complications in this respect. Infants born by caesarian section or with cord complications, as well as those with delayed respiratory adaptation, showed a higher incidence of atypical factor VII than the risk group as a whole.Atypical factor VII was not detected until the third day of life, irrespective of the prenatal or postnatal complications.These findings suggest that perinatal risk factors are associated with an alteration of factor VII synthesis.In honour of Prof. Dr. Goetze (Director of the Institute of Pathophysiology of the University Jena) on the occasion of his 65th birthday     

Use of Recombinant Factor VIIa for Bleeding in Children with Glanzmann Thrombasthenia

Glanzmann thrombasthenia is a very rare inherited platelet function disorder in which bleeding may be extremely difficult to stop. Recombinant factor VIIa is one of the alternative treatments for bleeding. The authors report here their experience with the use of factor VIIa, which may be useful for arresting bleeding in Glazmann thrombasthenia.     

Severe congenital factor X deficiency with intracranial haemorrhage

A Saudi Arabian infant with severe factor X deficiency who had had two intracranial haemorrhages is described. Attempts to raise his factor X level and improve his prothrombin time (PT) and partial thromboplastin time (PTT) by using vitamin K, oestradiol and danazol have failed. New therapeutic trials are necessary for patients with severe forms of this rare disorder.Abbreviations PT prothrombin time - PTT partial thromboplastin time - FFP fresh frozen plasma     

Use of recombinant factor VIIa for bleeding in children with Glanzmann thrombasthenia

Glanzmann thrombasthenia is a very rare inherited platelet function disorder in which bleeding may be extremely difficult to stop. Recombinant factor VIIa is one of the alternative treatments for bleeding. The authors report here their experience with the use of factor VIIa, which may be useful for arresting bleeding in Glazmann thrombasthenia.     

儿童髓母细胞瘤的临床特点及预后相关因素分析

目的通过分析儿童髓母细胞瘤的临床特点、治疗方法和患者预后的关系,探索影响儿童髓母细胞瘤预后相关因素。方法收集2004年至2014年复旦大学附属儿科医院收治且术后病理证实为髓母细胞瘤患儿的病例资料,对所收集数据进行分组,采用单因素Kaplan-Meier法进行生存分析,统计各组病人的总体生存时间及累计生存率,采用Log-Rank检验分析各组病人累计生存率差异,采用Cox回归进行多因素分析,探讨儿童髓母细胞瘤临床因素与生存时间、生存结局的关联性。结果单因素分析结果认为,临床症状阳性数(P=0.039)、M分期(P=0.009)、术后放疗(P=0.001)、术后化疗(P=0.018)、肿瘤复发(P=0.04)是髓母细胞瘤患儿预后的影响因素;Cox多因素分析结果认为术后放疗(OR=0.291,95%置信区间:0.120~0.706,P=0.006)和化疗(OR=0.095,95%置信区间:0.024~0.384,P=0.001)是影响髓母细胞瘤患儿预后的保护因素;性别、年龄、肿瘤位置、T分期、肿瘤切除程度、病理分型等因素未发现与预后有关(P>0.05)。结论术后是否接受放疗、化疗对患儿预后影响较大,而临床症状的个数、M分期、肿瘤复发对患儿预后的判断价值有限,性别、年龄、肿瘤位置、T分期、肿瘤切除程度、病理分型等因素则与预后无关。     

Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two-year-old child

Muntean W, Zenz W, Finding K, Zobel G, Beitzke A. Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two-year-old child. Acta Prediatr 1994;83:84–7. Stockholm. ISSN 0803–5253
A two-year-old infant developed an inhibitor to factor V after cardiac surgery, with application of fibrin sealant containing bovine thrombin. Investigation of this inhibitor by means of inhibition experiments and immunoblot analysis revealed that the inhibitor reacted strongly with bovine, but only weakly with human factor V. Plasmapheresis proved effective in increasing factor V levels. This patient provides further evidence that exposure to topical thrombin preparations may lead to the development of inhibitors in the postoperative period that may cause bleeding complications.