东北地区正常人群St14(DXS52)位点VNTR多态分布及在甲型血友病基因诊断中的应用

目的探讨中国正常人群Ｓｔ１４（ＤＸＳ５２）位点ＶＮＴＲ多态分布，为甲型血友病基因诊断提供依据。方法应用ＰＣＲ方法检测东北地区遗传上无相关的正常汉族个体６０人，男１２人，女４８人，总计１０８条Ｘ染色体。结果共检出８种等位基因片段，最短片段为０．７ｋｂ（Ａ），依次为１．３（Ｂ），１．３９（Ｃ），１．５７（Ｄ），１．６３（Ｅ），１．６９（Ｅ），２．１（Ｇ），２．４ｋｂ（Ｈ）等不同长度的等位片段，其等位基因频率为Ａ０．３９，Ｂ０．０４６，Ｃ０．０８３，Ｄ０．２３２，Ｅ０．１１１，Ｆ０．１３０，Ｇ０．００９，Ｈ０．００９等，其ＰＩＣ为７６．３６％。利用此ＶＮＴＲ多态作为遗传标记，对３个甲型血友病家系进行连锁分析，在一个家系中确定了一名女性为正常人，而非携带者；在另两个家系中各检出一名男性胎儿患者。结论Ｓｔ１４（ＤＸＳ５２）位点ＶＮＴＲ多态是对甲型血友病基因诊断很有应用价值的遗传标记。     

一例大片段重复变异导致血友病A的分析

目的:报告1例由罕见变异导致的重型血友病A(hemophilia A,HA),并探讨大片段重复变异的致病机制。方法:先后进行 F8基因第22内含子及第1内含子倒位检测、Sanger测序以及多重连接探针扩增(multiple ligation-dependent probe amplification,MLP...     

凝血酶生成试验在血友病患者中的应用

目的：探讨凝血酶生成试验在血友病患者中的应用。方法：收集134例血友病患者[其中血友病A（HA）114例，血友病B（HB）20例1的临床资料，根据FⅧ：C／FIX：C不同，将无FⅧ／FⅨ抑制物的132例HA／HB患者分成重型（FⅧ：C／FIX：C〈1％）、中型（FVIU：C／FIX：C1％～5％）及轻型（FⅧ：C／FIX：C6％～25％）3组，检测凝血酶生成、FⅧ：C／FIX：C及其抑制物。结果：重型HA／HB患者与轻型者比较，出血频度及凝血酶生成各指标差异均有统计学意义（P〈0．01）；而重型者与中型者比较，除延迟时间和达峰时间差异有统计学意义外（P〈0．01），其余指标差异均无统计学意义；中型者与轻型者比较，除延迟时间和达峰时间差异无统计学意义外，其余指标差异均有统计学意义（P〈0．01）。HA／HB患者的出血频度与FⅧ：C或FIX：C无关（P=0．16），而与凝血酶生成潜力（ETP）密切相关（P=0．0001）：结论：凝血酶生成试验可作为预测HA／HB患者出血风险的有效手段。     

Genu recurvatum in hemophilia: a case report

Hemorrhages in the musculoskeletal system of patients with hemophilia give rise to a number of disabilities requiring rehabilitative measures. The knee is the most commonly affected joint. Recurrent hemorrhages in the knee joint can cause arthropathy and flexion deformity. The current literature does not reveal development of genu recurvatum from repeated hemorrhages. This report presents a patient with hemophilia who developed a genu recurvatum deformity. We have discussed the clinical presentation, probable cause, and the management of the patient, and have included a brief review of the epidemiology of this deformity along with management options.     

利福平化学性滑膜切除术治疗血友病慢性滑膜炎

目的 了解利福平化学性滑膜切除术对血友病慢性滑膜炎的疗效.方法 报道成都市妇女儿童中心医院首例用利福平化学性滑膜切除术治疗血友病慢性滑膜炎并进行文献复习.患儿9岁,诊断为血友病甲（重型）,左膝关节慢性滑膜炎.坐轮椅,左膝关节明显肿胀、压痛,关节活动明显受限.入院后输注FⅧ,使FⅧ活性＞30％,立即在B超引导下行关节内注射利福平,每周1次,共9次.结果 随访3年,膝关节外观正常,行走及常规活动正常,左膝关节未再发生出血事件.结论 利福平用于化学性滑膜切除术,控制出血疗效好,操作方便,药源丰富,价格低廉,尤其适用于儿童.     

The safety of pharmacologic options for the treatment of persons with hemophilia

ABSTRACT

Introduction: The mainstay of treatment of hemophilia A and B is the replacement of the congenitally deficient coagulation factor through the intravenous infusion of specific concentrates (factor VIII, FVIII, in hemophilia A; factor IX, FIX, in hemophilia B). Several commercial brands of FVIII or FIX products extracted from human plasma or engineered using recombinant DNA technology are available.

Areas covered: We analyze the safety aspects of plasma-derived and recombinant FVIII and FIX products licensed in Europe, focusing on their pathogen safety and inhibitor and thrombosis risks. The safety aspects of bypassing agents (i.e., activated prothrombin complex concentrates and recombinant activated factor VII) used for treatment of bleeding episodes in inhibitor patients will be also briefly discussed.

Expert opinion: The analysis of the published literature documents the high degree of safety from pathogen risk for both plasma-derived and recombinant products available for hemophilia treatment. The main threat to factor concentrate safety is represented by the development of neutralizing alloantibodies against the infused coagulation factor, which in hemophilia A seem to occur more frequently following the administration of recombinant than plasma-derived FVIII products. Great expectations are placed on newer products, particularly on those based upon mechanisms of action other than FVIII replacement.     

Prenatal Diagnosis in a Family at Risk for β‐Thalassemia and Hemophilia A: An Uncommon Association

β‐Thalassemia (thal) is an autosomal recessive disorder with a prevalence of 2–3% in Indians, while hemophilia A is X‐linked with a prevalence of 1 in 5,000–10,000 male births. The chances of both these disorders being present together is extremely rare (1 in 250,000). We report an interesting consanguineous family from Western India with a combination of these two disorders, which was referred to us for prenatal diagnosis.     

Relationship between red blood cell distribution width and kidney function tests in a large cohort of unselected outpatients

Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI), also called plasma procarboxypeptidase B or U, is one of the modulators of fibrinolysis in blood. Pro-TAFI is activated by thrombin/thrombomodulin complex or by plasmin to a carboxypeptidase B-like enzyme (TAFI) of 35.8?kD molecular weight. TAFI spontaneously becomes inactive as a result of a temperature-dependent conformational change in the protein (TAFIi). In this study, pro-TAFI, total TAFI antigen and TAFI-TAFIi antigen levels were measured in 32 patients with hemophilia A, 4 patients with hemophilia B, 21 patients with von Willebrand disease (VWD) and 13 healthy controls. A statistically significant decrease in pro-TAFI was found in all groups (10.72±4.57?mg/L (p&;lt;0.001); 8.00±2.35?mg/L (p&;lt;0.01) and 8.98±2.33?mg/L (p&;lt;0.001) for hemophilia A, hemophilia B and VWD, respectively) compared to controls (17.85±4.61?mg/L). A statistically significant increase in TAFI-TAFIi antigen was found in hemophilia A (1.05±1.01?mg/L) (p&;lt;0.05) and in VWD patients (0.96±1.01?mg/L) (p&;lt;0.05) compared to controls (0.55±0.36?mg/L). There was no difference in total TAFI antigen levels between any group of patients and the controls. Neither did pro-TAFI nor TAFI-TAFIi levels differ within the group of hemophilia A patients in relation to severity (mild, moderate and severe) or among the VWD patients in relation to subtype (type 1, type 2A and type 3). These findings indicate an increased conversion of pro-TAFI to TAFI and/or TAFIi in patients with bleeding disorders. As thrombin generation is seriously impaired in these patients and almost absent in hemophilia A and B and in type 3 VWD, it is possible that plasmin mediates pro-TAFI activation in these patients. Enhanced fibrinolysis via generation of plasmin has previously been reported in hemophilia and VWD. Activation of pro-TAFI by plasmin may be a feedback mechanism that counterbalances increased fibrinolysis in patients with bleeding disorders. The relationship between the TAFI activation pathway and bleeding complications associated with hemophilia A, hemophilia B and VWD requires further investigation.