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。     

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。     

应用凝血因子抑制物检测方法检出获得性血友病A2例

获得性血友病A,又称」肝血友病性血因于抗体增多症。临床上较少见,加之受某些试验条件限制,也难以排除漏诊之可能。最近我所应用检测凝血因于抑制物的方法,发现2例获得性血友病A。现报告如下。1资料与方法1．1检测对象病例1,女,77岁,以“肉眼血尿”入院,皮肤亦见片状瘀斑,针刺后不易全血,胸片显示肺纤维,膀胱镜检可见右侧输尿管口出血,无其他病史及家族史,凝血象筛检：TT、PT均正常纤维蛋白原,Fg5．2g／L,APTT＞140s,正浆纠正＞140s,进～步检查Ⅷ：C1．46％,FⅧ抑制物16Bethesdaμ／ml血浆,据此诊断为“肺纤维化伴…     

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.     

359例血友病A实验室诊断数据回顾分析

目的 调查分析本院血友病A患者的实验室诊断数据,了解医院就诊血友病A临床分型、抑制物存在情况及获得性血友病的诊断思路,为临床诊断和治疗提供证据.方法 对患者进行活化部分凝血活酶时间(APTT)和Ⅷ因子活性(FⅧ∶C)检测,抑制物筛查采用APTT纠正试验做定性判断,阳性者用Nijmegen定量检测抗体.结果 359名血友病A患者以重型和中型居多(共占81％),亚临床型仅14例.抑制物筛查22例阳性,FⅧ抗体定量检测平均抗体滴度35 BU.获得性血友病1例;2例患者同时存在FⅧ∶C、FⅨ∶C低下和抑制物阳性.结论 医院就诊的血友病A患者主要为重型和中型,亚临床型少见;FⅧ抑制物筛查及抗体滴度在临床治疗方案选择中及其重要;获得性血友病诊断思路应该为实验室数据结合临床、遗传学、自身免疫性检查等.     

特发性肺纤维化伴获得性血友病A一例

获得性血友病Ａ或称非血友病性ＦⅧ抗体增高为少见疾病。最近我们遇到１例,现报告如下。患者,女,７７岁。１９９８年３月７日因突发右腰部疼痛伴血尿１周入院。患者于入院１周前突感右腰部阵发性绞痛,并出现血尿,尿色暗红,尿中有絮状血凝块。近期患者有不定时轻微咳...     

获得性血友病A免疫抑制剂的治疗进展

获得性血友病A是一种发病率极低但病死率较高的自身免疫性疾病。多种原因导致患者体内产生了特异结合、灭活凝血因子Ⅷ的凝血因子抑制物而发病。患者在其体内凝血因子抑制物完全清除之前都处于严重出血甚至致死的风险之中。因此,如何正确合理地选择免疫抑制剂来进行抑制物清除治疗是消除患者出血风险,达到长期稳定完全缓解以及最终治愈该病的重要环节。     

一例伴高滴度抗体血友病A患者施行截肢术

血友病A抗体形成通常被认为是外科手术的禁忌证。在充分术前准备的前提下,我们对一例重型血友病A伴高滴度抗体及严重感染患者施行急症左下肢截肢术。病例资料患者,男,门岁。确诊血友病A12年。本次由于左膝关节极度肿胀、坏死伴全身严重感染2周入院。患者入院时神萎,痛苦及贫血面容,体温39．6t,呼吸ZI次lmin,血压98168＊g门地二o．133kPa）。心率92次7i,呼吸音粗,腹软、肝、脾肋缘下未及。双下肢严重萎缩,两侧踝、膝、肘关节畸形,左膝关节肿胀,周径达84cm,表面呈棕黑色,有一小窦道向外流出黑色脓血液;左小腿肿胀,广泛瘀斑…     

血友病A伴抑制物患者严重出血的治疗及护理

目的 探讨伴发抑制物的血友病患者严重出血时的治疗及护理。方法 对12例血友病A伴抑制物患者采取积极的治疗及精心护理。结果 12例患者（32例次住院）出血症状全部好转,痊愈出院。结论 血友病突出的临床表现是自发性出血或轻微损伤后出血不止,而伴发抑制物使出血更严重。因此,密切观察患者出血情况,准确、及时实施治疗,做好症状护理、心理护理及健康教育尤其重要,使患者从心理和生理上得到最佳康复。     

The rare coexistence of high titer inhibitor development and gastrointestinal stromal tumor in a patient with severe hemophilia: A case report

Hemophilia is a hereditary disease with impaired blood coagulation due to a genetic deficiency of blood coagulation factors. The development of inhibitors further complicates the course of the disease and management. The case is here reported of a haemophilia patient who presented with coexisting development of high titer inhibitor with Gastrointestinal Stromal Tumor (GIST) diagnosis and was admitted with upper gastrointestinal system bleeding. The patient had no prior history of inhibitor presence. During all procedures including surgery, excellent hemostasis was achieved with rFVIIa treatment and no hemorrhagic complication was observed. To the best of our knowledge, this constitutes the first reported case of GIST associated with inhibitor development in a hemophilia A patient.     

Immune tolerance induction for the eradication of inhibitors in patients with hemophilia A

Background: Both genetic and environmental factors contribute to the formation of alloantibodies that bind to functional domains on the Factor VIII (FVIII) molecule and inhibit its function. Patients with hemophilia A who develop high-titer inhibitors are at increased risk for serious hemorrhage and disability, particularly arthropathy, because bleeding events do not respond to standard therapy. Immune tolerance induction (ITI) is usually attempted to eradicate newly diagnosed inhibitors, restore replacement FVIII pharmacokinetics, and improve bleed management and quality of life. Objective: This paper summarizes regimens used for ITI, predictors of success and failure, and adjunctive therapies for patients failing ITI therapy. Methods: This is a systematic review of published reports on ITI regimens, data from registries capturing response rates and predictors of success, and reports of adjunctive treatments used to enhance ITI therapy. Results/conclusion: Many issues remain unresolved, chief among them optimal dose and dosing regimen, choice of FVIII product, and the role of adjunctive therapy. Resolution of these issues, as well as new approaches to inhibitor management, may come from ongoing basic science research and clinical trials.     

Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort

Summary.  Background and objectives:  he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab in up to 57% of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias of reporting good outcomes and relatively short follow up, a consecutive cohort of all patients treated in the UK with prolonged follow up was analyzed. Methods:  A national survey of all Comprehensive Care Haemophilia Cente in the UK. Results:  A total of 15 patients were reported of whom six (40%) achieved a negative inhibitor titer by Bethedsa assay. Durable responses were unusual, observed in only 14% of cases. Clinically significant responses with either a negative inhibitor or an inhibitor titer < 5 BU mL⁻¹ and no spontaneous bleeding with FVIII replacement were observed in seven (47%) cases. Concomitant use of FVIII appeared to be important. Of the 12 patients treated with rituximab and FVIII, six (50%) achieved a negative inhibitor titer and seven (58%) had a clinically beneficial response. None of the three patients treated without FVIII responded. Conclusions:  hese data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon.     

同时存在血友病A及血友病B患者家系的基因诊断

目的:对1个同时存在血友病A(HA)及血友病B(HB)患者的家系进行分子发病机制研究,并对家系女性成员进行携带者检测。方法:采用活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(Fg)、凝血因子Ⅷ(FⅧ)活性(FⅧ:C)、FⅨ活性(FⅨ:C)及血管性血友病因子(vWF)等测定进行HA及HB表型诊断;用长链聚合酶链反应(LD-PCR)进行F8基因内含子22倒位检测,2组序列特异的PCR对F8基因内含子1倒位进行检测;采用直接核苷酸测序法对F9基因各外显子及其侧翼序列进行检测,联合F9基因相关的6个微卫星位点(DXS8094、DXS1211、DXS1192、DXS102、DXS1227及DXS8013)进行家系遗传连锁分析。结果:先证者1是由F8基因内含子22倒位引起的HA。先证者2是由F9基因突变nt32772A→T突变(p.Ser365Cys,GI:22385320)引起的HB,其突变基因遗传自其母亲,来源于先证者2外公的X染色体,其外公为该突变的体细胞和生殖细胞嵌合体,其阿姨口腔细胞DNA未检出该突变。结论:该家系2名先证者的基因诊断结果与表型诊断相符。单碱基延伸法可用于突变嵌合率的检测,并为血友病散发家系的突变来源提供可靠的信息。     

Orthotopic liver transplantation in a patient with severe hemophilia A: a life-saving treatment for the first Italian case

Summary Clinical cure of hemophilia A by orthotopic liver transplantation has been reported in 11 cases. We describe the first successful Italian case. A 27-year-old man had cirrhosis caused by previous infections with the hepatitis B, C and D viruses following life-long treatment with factor VIII concentrates made from large plasma pools. He was, however, seronegative for the human immunodeficiency virus. In the year before transplantation, life-threatening gastrointestinal bleeding due to severe esophageal varices required a large transfusion regimen (on average, 13 bags of red cell concentrates and 35,000 U of factor VIII/week). To perform orthotopic liver transplantation 8,000 U of factor VIII were given during surgery together with 10 bags of red cells and 11 of fresh-frozen plasma. Intraoperative bleeding was not different from that of non-hemophilic patients undergoing orthotopic liver transplantation. No additional factor VIII was used after transplantation and factor VIII levels in plasma were always above 50 U/dl, reaching the highest value of 184 U/dl on day 4 post transplantation. He was discharged from hospital 10 weeks after trans-plantation with factor VIII levels of 68 U/dl. All virological markers are currently negative, except anti-hepatitis C virus antibodies. In this patient orthotopic liver trans-plantation was a life-saving treatment for end-stage cirrhosis and a cure for hemophilia A.     

Hepatitis C treatment with triple therapy in a patient with hemophilia A

We report a case of successful treatment of chronic hepatitis C infection with telaprevir-based triple therapy in a patient with hemophilia A complicated by factor VIII inhibitor. A twenty-two years old male with hereditary hemophilia A and high-titer factor VIII inhibitor was taking maintenance doses of recombinant factor VIII. He visited our clinic for treatment of his chronic hepatitis C with the newly instituted protease inhibitor based therapy. He was diagnosed with hepatitis C genotype 1a at one year of age. He was initiated on telaprevir, ribavirin and peg-interferon for treatment of hepatitis C and qualified for response-guided therapy. He completed treatment at 24 wk with minimal adverse effects. Notably, after 4 wk of hepatitis C treatment, his factor VIII inhibitor screen was negative and the dose for recombinant factor VIII decreased by half of the initial dosing before he was treated for hepatitis C. We suspect that suppressing hepatitis C may help decrease factor VIII inhibitor level and the need for recombinant factor VIII.