血友病A患儿凝血因子Ⅷ抑制物相关临床研究

目的探讨血友病A(HA)患儿凝血因子Ⅷ(FⅧ)抑制物产生的相关因素及抑制物产生前后出血与关节病表现的差异。方法对2015年1月至2018年8月河南省血友病管理中心登记收治的381例16岁以下HA患儿进行回顾性分析。结果381例HA患儿中,轻型116例(30.4%),中间型196例(51.4%),重型69例(18.1%)。FⅧ抑制物阳性患者54例(14.2%),高滴度、低滴度分别为22、32例。血友病家族史与FⅧ抑制物阳性相关[P<0.001,OR=3.299(95%CI 1.743~5.983)];高强度暴露与FⅧ抑制物的产生相关[P=0.002,OR=2.587(95%CI 1.414~4.731)]。高强度暴露与高滴度FⅧ抑制物产生相关[P=0.001,OR=8.689(95%CI 2.464~30.638)]。54例HA患者产生抑制物后,总体关节年出血率、创伤性年出血率增加(z=-3.440,P=0.001;z=-2.232,P=0.026),而非关节年出血率、自发性年出血率与抑制物产生前比较差异无统计学意义(z=-1.342,P=0.180;z=-1.414,P=0.157)。关节超声评分较产生抑制物前差异无统计学意义(z=-0.632,P=0.527)。结论血友病家族史、高强度暴露可增加HA患儿发生FⅧ抑制物的风险,且高强度暴露可增加HA患者出现高滴度抑制物的风险。     

36例血友病A相关抑制物检测分析

目的 研究替代治疗后血友病A患者抑制物存在状况,以指导临床治疗方案的调整.方法 对病人进行活化部分凝血活酶时间(APTT)测定和Ⅷ因子活性(FⅧ:C)检测,抑制物检测采用APTT纠正试验做定性判断,阳性者用Nijmegen方法进行抗体定量检测.结果 全部36例血友病A患者替代治疗后FⅧ抑制物定性试验有2例出现阳性,FⅧ抗体定量检测抗体量分别为33BU和61BU.结论 通过对血友病A患者替代治疗后FⅧ抑制物的检测分析,有利于了解血友病A患者的替代治疗效果及预后.     

血浆脑利钠肽在川崎病患儿诊断中的临床价值

目的 研究血浆脑利钠肽(brain natriuretic peptide,BNP)在川崎病(Kawasaki disease,KD)患儿中的变化及其与心功能的关系,探讨其在KD诊断中的临床应用价值.方法 前瞻性观察2007年2月至2009年4月间青岛市儿童医院心血管组收治的KD患儿43例(KD组),年龄5个月至8岁,平均(2.3±0.6)岁,均符合KD诊断标准,且除外心肌炎、心肌病、先天性心脏病等原发心脏疾病.对照组为30例健康体检儿童,年龄及性别与KD组比较差异无统计学意义(P>0.05).KD组于急性期、恢复期各采血1次,健康对照组随机采血1次,采用酶联免疫吸附法(ELISA)测定血浆BNP浓度,KD组常规超声心动图检测左室射血分数(left verdricular ejection fraction,LVEF)、左室短轴缩短率(left Yentrietdar shorten fraction,LVSF)、心脏指数(cardiac index,CI)及舒张期二尖瓣口血流频谱E/A比值.组间比较采用成组t检验,组内比较采用配对t检验,相关分析采用直线相关分析法,以P<0.05为差异具有统计学意义.结果 KD患儿急性期BNP水平为(517.26±213.40),ng/mL,恢复期为(91.56±47.97)ng/mL,两期比较差异具有统计学意义(P<0.01);急性期BNP水平亦明显高于健康对照组[(37.55±7.56)ng/mL],两组比较差异具有统计学意义(P<0.01);心功能参数LVEF,LVSF,CI急性期低于恢复期,两期比较差异均具有统计学意义(P<0.05),E/A比值两期比较差异无统计学意义(P>0.05);KD患儿急性期血浆BNP水平与反应心脏收缩功能指标LVEF,LVSF,CI均呈负相关(P<0.05),而与舒张功能E/A无明显相关性(P>0.05).结论 KD急性期血浆BNP浓度异常升高,心脏收缩功能下降,两者呈负相关.血浆BNP浓度检测对川崎病的早期诊断具有重要意义.     

血友病A患者凝血因子Ⅷ抑制物筛查及分析

本研究通过检测重型血友病A(hemophilia A,HA)患者凝血因子Ⅷ(FⅧ)抑制物,探讨抑制物阳性患者基因突变情况.选取58例一期法检测FⅧ:C均小于1% HA患者,以APTT法为基础进行FⅧ抑制物筛查,筛查阳性者用Bethesda法进行FⅧ抑制物定量分析.以基因组DNA为模版,对抑制物阳性患者FⅧ12、14、16外显子进行基因扩增,PCR产物通过直接测序检测突变情况.结果表明:58例HA患者中4例(6.9%)抑制物检测为阳性,FⅧ12、14、16外显子基因均未发现基因突变.结论:本组病例HA患者抑制物阳性率低于国外文献报道,抑制物产生的原因有待于进一步研究.     

院外延续性护理在血友病A患儿中应用

目的探讨院外延续性护理在血友病A患儿中的应用效果。方法选取血友病A患儿32例(1个月~12岁儿童13例,13~18岁青少年19例),实施院外延续性护理干预。针对1个月~12岁儿童家长和13~18岁青少年开展调查,评价干预前后患儿或家长的焦虑自评量表(SAS)评分、对疾病知识的掌握情况和对护理工作满意度,以及护理前后患儿每月出血次数。结果实施院外延续性护理后血友病A患儿或家长SAS评分低于护理前,疾病掌握情况评分和护理满意度评分均高于护理前,差异有统计学意义(P0.05,P0.01)。实施院外延续性护理后患儿出血频次为(1.9±1.6)次/月,低于护理前的(2.8±1.2)次/月,差异有统计学意义(P0.05)。结论院外延续性护理能够减少血友病A患儿出血频次和焦虑情况,提高患儿和家长对疾病的认识,提高护理满意度。     

获得性血友病A的诊断

性血友病A(Acquired Hemophilia A,AH-A)是由于非血友病患者体内自发性产生针对凝血因子Ⅷ(FⅧ)的特异性自身抗体而引起的一种出血病[1,2].AH-A以突发性严重出血为其主要临床特征,诊断和鉴别诊断常需依赖实验室检测.诊断的准确和及时对于患者的生存和预后极为重要.我们结合文献对AH-A诊断的进展做一综述,以探讨AH-A的规范化诊断过程.     

遗传因素与血友病A凝血因子抑制物产生的研究进展

血友病A(Hemophilia A,HA)是一种X连锁隐性遗传性凝血功能障碍性疾病,由编码FⅧ(凝血因子Ⅷ)的基因突变引起的凝血因子不足或功能障碍所致。血友病A的治疗,在目前仍以凝血因子替代治疗为主。反复输注凝血因子制剂后会产生针对FⅧ的抗体,这是HA治疗的严重并发症之一。关于抑制物发生率,国内外文献报道差异较大。影响凝血因子抑制物产生的因素多种多样,主要分为遗传因素和环境因素,其中遗传因素是抑制物产生的主要因素。本综述主要阐述国内外HA凝血因子抑制物产生的相关遗传危险因素的研究现状。     

血浆血管性假血友病因子对肝纤维化的诊断价值

目的 通过检测各组肝病患者血浆的血管性假血友病因子（VWF）水平与血清Ⅲ型前胶原蛋白（PⅢ）、透明质酸（HA）、层粘连蛋白（LN）之间的比较来进一步探讨血VWF对肝纤维化的诊断价值。方法 用VWF Laurell免疫火箭电泳法,PⅢ、HA、LN均用放射免疫法。结果 发现VWF在各肝病组均比对照组明显升高（P＜0.01）;其血浓度肝硬变＞慢性活动性肝炎＞急性肝炎。VWF与PⅢ在慢性活动性肝炎组中两者虽直线相关（P＜0.05）。结论 VWF血浓度可反映肝损伤及肝纤维化的程度,并随着急性肝炎、慢性活动肝炎及肝硬变的发展呈进行性升高。     

血浆凝血酶激活的纤溶抑制物和血清同型半胱氨酸在急性脑梗死中的诊断价值

目的探讨血浆凝血酶激活的纤溶抑制物(TAFI)与血清同型半胱氨酸(Hcy)水平在急性脑梗死(ACI)中的诊断价值。方法检测100例ACI患者(ACI组)和100名体检健康者(正常对照组)的血浆TAFI水平和血清Hcy水平。采用受试者工作特征(ROC)曲线评估TAFI和Hcy诊断ACI的效能。采用Pearson相关分析评估TAFI与Hcy的相关性。结果与正常对照组比较,ACI组血浆TAFI水平降低(P0.05),血清Hcy水平升高(P0.05)。ACI组TAFI、Hcy的阳性率分别为59%、65%,均高于正常对照组(1%、5%)(P0.05)。ROC曲线分析结果显示,TAFI、Hcy单项检测和联合检测诊断ACI的曲线下面积(AUC)分别为0.907、0.828、0.949,最佳临界值分别为22.22μg/mL、14.95μmol/L、0.507,敏感性分别为78.3%、65.2%、88.0%,特异性分别为95.0%、100.0%、97.0%。Pearson相关分析结果显示,ACI组TAFI与Hcy无相关性(r=-0.075,P0.05)。结论 TAFI和Hcy在ACI的诊断中有一定的价值。     

一例血友病A伴抑制物免疫耐受诱导治疗的护理

血友病A是一种X染色体连锁的隐性遗传性出血性疾病,为凝血因子Ⅷ（FⅧ）基因异常所致,其临床特点为自发性关节出血和／或深部组织／肌肉出血。FⅧ替代治疗已公认为血友病A的最佳疗法,FⅧ抑制物的产生是其最严重的并发症。     

Diagnostic value of the glycerol lysis test

The diagnostic value of the standard glycerol lysis test (GLT) has been evaluated by studying 95 cases of hereditary spherocytosis (HS), 513 beta- and 25 alpha-thalassemia trait (Th) carriers, 170 iron-deficient patients (ID), and 217 patients with miscellaneous hematological conditions. The sensitivity of the test, at 95% specificity, was 97% for beta-Th, 53% for ID, and only 36% for HS, so that the predictive value of a positive result is practically nil for HS, 50% to 85% for Th, and 10% to 35% for ID, depending on the prevalence ratio of the disease in the examined population. The technical variability of GLT, explored by a proper experimental design, was found to be rather high, its main components being repeatability and variability of reagent preparations. The dependence of the results on operators was negligible. It is concluded that GLT is not suitable as a laboratory test for the detection of abnormalities in red cell osmotic fragility because of its very low sensitivity toward increased fragility. For decreased red cell osmotic fragility, the sensitivity of GLT is high; however, it is less valuable than the traditional 0.35% NaCl method as mass screening test for the detection of beta-Th, giving more false positive results.     

Diagnostic value of the bilirubin load test

Analysis of the results of 270 examinations of the absorption/excretion function of the liver carried out with the use of Bergmann-Eilbott's test in patients with various diseases has demonstrated a high sensitivity of the test. No complications or side effects have been recorded.     

自制混合血浆在血浆纠正试验中的临床应用初探

目的通过比较不同温度保存的自制混合血浆与正常混合血浆对血浆纠正试验的影响,探讨自制混合血浆在血浆纠正试验中的临床应用价值。方法收集凝血酶原时间(PT)≥18.0s和(或)活化部分凝血活酶时间(APTT)≥52.0s的血浆标本35份,分别与正常混合血浆(A组)、-80℃(B组)和-20℃(C组)保存的自制混合血浆按体积1∶1混合后做血浆纠正试验,即混合后立即测定PT和(或)APTT,37℃孵育1h后再次检测。计算35份标本可被正常混合血浆纠正的比例及3组的纠正率。结果 88.57%(31/35)可被正常混合血浆立即纠正,4例未被纠正,其中1例孵育后比孵育前测定时间更加延长,占2.86%;3例孵育前后测定结果不变,占8.57%。在PT延长的血浆纠正试验中,各组之间纠正率差异无统计学意义(P0.05)。在APTT延长的纠正试验中,孵育前A组、B组和C组的纠正率分别为(32.93±16.17)%、(27.56±23.48)%和(13.70±12.87)%,A组和B组之间纠正率差异无统计学意义(P0.05),其余各组之间纠正率差异有统计学意义(P0.05)。结论 -80℃保存的自制混合血浆可代替商品化的正常混合血浆进行血浆纠正试验。     

Diagnostic and predictive value of the silkworm larvae plasma test for postoperative infection following gastrointestinal surgery

OBJECTIVE: To determine whether the silkworm larvae plasma (SLP) test is a reliable diagnostic marker of infection in patients with infectious complications following gastrointestinal surgery. DESIGN: Prospective study. SETTING: Department of Surgery, University Hospital, Shiga University of Medical Science. PATIENTS: One hundred and twelve adult patients undergoing gastrointestinal surgery INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine of 112 patients developed infectious complications (infected group). Seven patients with sepsis (severely infected group) and 32 patients without sepsis (minor infected group) were observed. The operation time, blood loss, and age were significantly greater in both infected groups than in the noninfected group. The systemic inflammatory response syndrome score on postoperative day (POD) 1 and POD7 was highest in the severely infected group. The increase in C-reactive protein on POD3 and POD7 was significantly higher in both infected groups than in the noninfected group. White blood cell counts on POD7 were elevated significantly higher in the severely infected group than in the other groups. Immediately after surgery, SLP activity significantly increased compared with presurgery in all groups and was significantly higher in the minor and severely infected groups than in the noninfected group. The increased SLP activity returned to preoperative levels in the minor and noninfected groups; however, SLP activity in the severely infected groups remained high throughout the observational period. The most significant factor and time point that predicted infectious complications were the SLP test on POD1; sensitivity 66.7%, specificity 90.4%, positive and negative predictive values 78.8% and 83.5%. The area under the receiver operating characteristic curve for the SLP test was 0.813 +/- 0.046. CONCLUSIONS: The SLP test appears to be a useful marker of diagnosis and prediction of infectious complications following gastrointestinal surgery. Moreover, the SLP test may be able to evaluate not only the existence but also the severity of infection in surgical patients.     

Diagnostic value of secretin provocation test.

Plasma gastrin response to the intravenously administered secretin was investigated in various clinical entities. The marked increase of plasma gastrin was found in response to secretin in a case of suspected Zollinger-Ellison syndrome in contrast to various degrees of plasma gastrin decrease seen in patients with ordinary or postoperative recurrent peptic ulcer. The diagnostic value of secretin provocation test was stressed especially in relation to differentiation between Zollinger-Ellison syndrome and recurrent ulcer due to retained pyloric antrum kept away from the food-passing route, both of which are characterized by hypergastrinemia and acid hypersecretion.     

Diagnostic value of the growth hormone-releasing factor stimulation test

Growth hormone (GH) responses to growth hormone-releasing factor (GRF) were evaluated in 55 children with growth failure. The study groups consisted of group 1, severe GH deficiency; group 2, partial GH deficiency; group 3, patients with prior cranial radiation for nonpituitary brain tumors; and group 4, children with idiopathic growth failure. Children in group 1 were unresponsive to GRF (mean GH peak +/- SEM, 1.6 +/- 0.5 ng/ml). Higher GH responses to GRF were observed in both groups 2 (17.2 +/- 4.1 ng/ml) and 3 (10.4 +/- 2.8 ng/ml). The highest GH responses to GRF were observed in group 4 (35.9 +/- 4.3 ng/ml). ANOVA revealed a significant difference between groups (F = 12.9; df = 3; p less than 0.01), and further analysis by the Scheffe and Student-Newman-Keuls tests revealed that group 4 was significantly higher than groups 1, 2, or 3 (p less than 0.05). These data suggest that GRF unresponsiveness is a reliable predictor of severe GH deficiency. In patients with partial GH deficiency or idiopathic growth failure, the GRF gives semiquantitative information about somatotrope responsivity to exogenous stimulation.     

Diagnostic value of the atropine test in the sick sinus syndrome

Altogether 63 patients with clinical signs of the SNWS (the 1st group), 16 patients with coronary heart disease and the latent SNWS (the 2nd group), 26 patients with heart coronary disease without disorder of sinus node function (the 3rd conventionally control group) and 60 healthy persons (the 4th control group) were examined. Atropine was administered i. v. to them all at a a dose of 0.02 mg/kg of the body mass. The heart beat rate (HBR) was measured before atropine injection as well as its increment after atropine injection. The HBR after atropine injection in the patients of the 1st group was significantly higher than that in the 2nd-4th groups; in the patients of the 2nd group the HBR was significantly less than that in the 3rd-4th groups. In the 3rd group the HBR was significantly less than that in the 4th group. An increased percentage of the HBR in the patients with clinical signs of the SNWS and in the healthy persons did not differ significantly (46.6 +/- 3.7% and 51 +/- 2.4% P greater than 0.2). The sensitivity of the atropine test in the patients of the 1st group was 76.3%. The test specificity was 93.3%. Among the patients with coronary heart disease the atropine test specificity was much less (65.4%).     

Diagnostic value of intravenous glucagon test in insulinoma.

The intravenous glucagon test was performed in 11 patients with insulinoma and the diagnostic significance of the test was studied in comparison with the glucose test, the tolbutamide test and the arginine test. The curves of plasma insulin following the intravenous administration of glucagon were markedly different and strange in those patients with insulinoma compared with the normal controls. The maximal levels of plasma insulin ranged from 85 to 400 muU/ml, exceeding the normal range in 10 out of 11 patients, or 91%. Increased levels in the maximal plasma insulin were observed in 63%, 100% and 56% through the glucose test, the tolbutamide test and the arginine test, respectively. The distribution of the insulin areas, calculated from the insulin curves during these tests, was shown to be similar to that of the maximal levels of plasma insulin. There was no significant correlations between the maximal levels of plasma insulin in the glucagon test and the glucose test, the tolbutamide test or the arginine test. The present experiment demonstrated that the intravenous glucagon test, next to the tolbutamide test, caused a large increase in plasma insulin, and therefore, that this test is one of the most useful tools among the provocation tests, for the diagnosis of insulinoma.     

心电图运动试验在高血压患者中的诊断价值

目的 :探讨心电图平板运动试验对有胸痛或胸闷症状的高血压患者患冠心病的诊断价值。方法 :以冠状动脉造影为对照 ,分析高血压组与非高血压组运动试验的敏感性和特异性 ;对运动试验阳性的高血压患者 ,比较冠状动脉造影阳性、阴性者静息血压、静息心电图ST T改变率、运动试验中ST段下移导联数、最大ST段下移幅度、运动时间、伴左心室肥厚比例等。结果 :高血压组与非高血压组运动试验的敏感性差异无显著性 ( 70 0 %对5 5 0 % ) ,但高血压组的特异性显著低于非高血压组 ( 4 1 2 %对 71 9% ,P <0 0 5 ) ;运动试验阳性的高血压患者 ,冠状动脉造影阳性、阴性者伴LVH分别为 2 8 6% ( 4例 )、70 % ( 7例 )。造影阳性者与阴性者比较 ,最大ST段下移幅度大、运动时间短 (P <0 0 5 )。结论 :伴有胸痛或胸闷症状的高血压患者 ,心电图运动试验阳性 ,但冠状动脉造影检查 ,部分患者大冠状动脉并无明显狭窄 ,故对合并LVH者、心电图运动试验中最大ST段下移幅度小、运动时间长的高血压患者 ,运动试验阳性不能作为冠心病的主要诊断依据。