血管性血友病因子裂解酶功能检测在血栓性血小板减少性紫癜诊断中的意义

目的 建立血栓性血小板减少性紫癜（TTP）的实验诊断方法,并用于TTP患者的诊断.方法 将微管透析前、后的正常人混合血浆、TTP患者血浆进行琼脂糖凝胶水平电泳与WesternBlot,分析TTP患者血浆中vWF多聚体的组成变化;以残余胶原结合力检测血管性血友病因子裂解酶（vWF-cp）的活性水平.结果 正常人混合血浆的vWF-cp活性为88.79%,4例TTP患者vWF-cp活性分别为8.90%,4.72%,28.73%,10.35%.正常混合血浆透析后只存在小分子量vWF;TTP患者血浆透析前、后的多聚体分布无变化或变化不明显.结论 残余胶原结合力测定结合裂解后的vWF多聚体电泳与Western Blot技术可准确分析vWF-cp活性与vWF多聚体结构组成的变化,为TTP诊断提供新的有用的实验诊断方法.     

血栓性血小板减少性紫癜9例分析

血栓性血小板减少性紫癜（TTP）是一种少见的血栓性微血管病,该病起病急骤,发展迅猛,常于短期内死亡。近年的研究表明,对此病早认识、早诊断,并给予血浆置换（PE）等治疗,可有效减少病死率。现将我院收治的9例患者报告如下。     

血栓性血小板减少性紫癜1例分析

对血栓性血小板减少性紫癜(TTP)1例分析如下。1病历摘要男,75岁。因腹部不适3个月、加重1d、寒战1 h于2010-07-28T12:00入院。查体:T37.2℃,神志清晰,精神不振,贫血貌,双下肢散在新鲜出血点,浅表淋巴结未触及肿大,牙龈无增生,胸骨无压痛,双肺呼吸音低,心律规整,腹平软,剑突下压痛,无反跳痛,肝脾未触及,肝区叩痛,无移动性浊音,四肢肌力、肌张力正常,各腱反射(++),病理征(-)。     

血栓性血小板减少性紫癜治疗的研究进展

血栓性血小板减少性紫癜(TTP)是一种血栓性微血管病,患者因严重缺乏血管性血友病因子裂解酶导致大量富血小板血栓堵塞血管,最终引发终末器官衰竭。血浆置换作为TTP治疗的基石,极大程度提高了患者的生存率。随着对TTP病理生理机制的进一步探索,逐渐涌现了其它类型的替代疗法、新型免疫抑制剂、靶向拮抗剂、基因治疗等新兴手段,有望进一步降低该病患者的死亡率和复发率。本文就TTP治疗的最新研究进展作一综述。     

血栓性血小板减少性紫癜

血栓性血小板减少性紫癜福建医科大学附属第一医院血液科（３５０００５）黄子洲概述血栓性血小板减小性紫癜（ｔｈｒｏｍｂｏｔｉｃｔｈｒｏｍｂｏ－ｃｙｔｏｐｅｎｉｃｐｕｒｐｕｒａ，ＴＴＰ）１９２５年由Ｍｏｓｃｈｃｏｗｉｔｚ首先报道。１９４７年Ｓｉｎｇｅｒ首先...     

遗传性血栓性血小板减少性紫癜5例临床分析北大核心CSCD

目的报道5例遗传性血栓性血小板减少性紫癜(cTTP)患者的临床表现及实验室检查特点,结合文献资料探讨cTTP的临床诊治方法。方法分析患者发病年龄、疾病表现、个人史、家族史、误诊情况等临床资料,观察血浆输注疗效和器官功能评估等治疗结局;结合血浆ADAMTS13活性测定及ADAMTS13基因突变分析,探讨cTTP临床表现、治疗结局与ADAMTS13基因突变间的相互内在联系。结果5例CTTP患者中男1例,女4例,发病年龄分别为1、9、12、19、31岁,主要临床表现为血小板明显减少、贫血及神经系统受累表现;既往多被疑诊为免疫性血小板减少症;2例女性患者因妊娠诱发,其他病例存在感染诱因。所有病例均检出ADAMTS13基因突变,基因突变区域与患者临床表现及器官损伤程度之间存在内在联系。治疗性和预防性血浆输注是有效的治疗方法。结论cTTP临床表现具有明显异质性,易被误诊而延误治疗。ADAMTS13活性检测和基因突变分析是重要诊断依据,预防性血浆输注可有效控制疾病发作。     

血栓性血小板减少性紫癜2例治疗分析

血栓性血小板减少性紫癜（TTP）是累及多器官系统的血栓性微血管病（TMA）,其特征为微血管病性溶血性贫血（MHA）、血小板减少和系统性微血栓所致的器官缺血。TTP中继发性占43％～66％,常继发于自身免疫性疾病、感染、药物、恶性肿瘤、妊娠和造血干细胞移植等。目前,血浆治疗为本病治疗的主要方法,其中血浆置换（PE）优于血浆输注（PI）,本文就2008-08／2008-11经PE治疗的2例TTP患者的诊疗经过分析如下。     

血栓性血小板减少性紫癜的护理体会

血栓性血小板减少性紫癜 (TTP)是以血小板减少性出血 ,微血管病变性溶血性贫血 ,神经精神症状和体征 ,肾脏损害和发热为特征的疾病。其中神经精神症状如头痛、嗜睡、意识障碍为突出的临床表现 ,且有阵发性多样易变的特点。临床罕见 ,发病率为每年 1 1 0 0万 ,发展快 ,病死率高。本科在 2 0 0 2年 2月～ 1 0月收治TTP患者 3例 ,均治愈出院 ,现将护理体会报告如下。1　临床资料例 1 ,男性 ,4 8岁。因左侧肢体乏力、神志不清 4d ,失语1d于 2 0 0 2年 2月 2 4日入院。查体 :T36 .4℃ ,BP1 30 / 85mm Hg,神志不清 ,呈浅昏迷状态 ,贫血貌 ,巩…     

血栓性血小板减少性紫癜误诊为特发性血小板减少性紫癜1例分析

对血栓性血小板减少性紫癜误诊为特发性血小板减少性紫癜1例分析如下.1病历摘要青年女性,1999年底无明显诱因出现皮肤出血点,查血常规示PLT 5×109/L,血小板抗体阳性(lgG或lgM不详),抗核抗体(+),骨髓象检查示:颗粒性巨核细胞增多,超声示脾稍大,诊断特发性血小板减少性紫癜,给予丙种球蛋白以及激素治疗,效果不佳.2000-08行脾脏切除,术后血小板维持在80×109/L左右,至2005年初病情平稳.2005-04无明显诱因再次出现皮肤出血点,月经量大,伴有低热,体温37.8℃.急诊入我院,查血常规示WBC 15×109/L,PLT 6×109/L,Hb 52 g/L,尿蛋白定性试验(+),考虑特发性血小板减少性紫癜复发,失血造成血红蛋白降低,给予丙种球蛋白冲击治疗4d,血小板无明显改变,一般状况恶化,并出现头痛伴癫痫发作,急诊行头颅CT检查未发现出血等异常表现.进一步完善检查,网织红细胞30％,血总胆红素33.4 μmol/L,间接胆红素26.5 μmol/L,乳酸脱氢酶1039 U/L,抗人球蛋白试验阴性,酸溶血试验阴性,游离血红蛋白160 mg/L.外周血破损红细胞占15％.骨髓象检查,红系增生极度活跃,巨核系以及粒系无异常,ESR27mm/h.综合分析:患者有血小板减少,溶血,伴发热,以及精神症状,结合临床表现以及实验室检查结果,诊断血栓性血小板减少性紫癜(TTP),急诊给予血浆置换同时给予潘生丁抗血小板聚集,后缓解出院.     

Platelet reactive conformation and multimeric pattern of von Willebrand factor in acquired thrombotic thrombocytopenic purpura during acute disease and remission

Summary. Background: Binding of von Willebrand factor (VWF) multimers of ultra‐large size to platelets is considered the triggering mechanism of microvascular thrombosis in thrombotic thrombocytopenic purpura (TTP). Objective: To assess the potential of VWF‐related measurements as markers of disease activity and severity in TTP. Methods: VWF antigen (VWF:Ag), platelet glycoprotein‐Ib‐α binding‐conformation (GPIb‐α/BC) and multimeric pattern were investigated in 74 patients with acquired TTP during acute disease, remission or both and 73 healthy controls. In patients with both acute and remission samples available, VWF ristocetin co‐factor activity (VWF:RCo) and collagen binding (VWF:CB) were also measured. The relationships of study measurements with the presence of acute disease and remission and with markers of disease severity were assessed. Results: VWF:Ag and VWF‐GPIb‐α/BC were higher in TTP patients than controls (P < 0.001 and 0.004). However, there was no statistically significant difference in VWF‐GPIb‐α/BC between samples obtained during acute TTP and remission. Larger VWF multimers were frequently lacking in acute TTP patients, who displayed ultra‐large multimers at remission. The degree of loss of larger VWF multimers correlated with the degree of abnormality of hemoglobin, platelet counts and serum lactate dehydrogenase (LDH) and was associated with low levels of both VWF:RCo/Ag and VWF:CB/Ag ratios. Conclusions: In TTP the platelet‐binding conformation of VWF is not exclusively present in acute disease, nor is it associated with its clinical and laboratory severity. The loss of larger VWF multimers, accompanied by low VWF:RCo/Ag and VWF:CB/Ag ratio values, represents an index of disease activity and severity of acute TTP in patients with severe ADAMTS‐13 deficiency.     

Humoral immune response to ADAMTS13 in acquired thrombotic thrombocytopenic purpura

Summary. The apparently spontaneous development of autoantibodies to ADAMTS13 in previously healthy individuals is a major cause of thrombotic thrombocytopenic purpura (TTP). Epitope mapping studies have shown that in most patients antibodies directed towards the spacer domain of ADAMTS13 are present. A single antigenic surface comprising Arg⁶⁶⁰, Tyr⁶⁶¹ and Tyr⁶⁶⁵ that contributes to the productive binding of ADAMTS13 to unfolded von Willebrand factor is targeted by anti‐spacer domain antibodies. Antibodies directed to the carboxyl‐terminal CUB1–2 and TSP2–8 domains have also been observed in the plasma of patients with acquired TTP. As yet it has not been established whether this class of antibodies modulates ADAMTS13 activity. Inspection of the primary sequence of human monoclonal anti‐ADAMTS13 antibodies suggests that the variable heavy chain germline gene segment VH1–69 is frequently incorporated. We suggest a model in which ‘shape complementarity’ between the spacer domain and residues encoded by the VH1–69 gene segment explain the preferential use of this variable heavy chain gene segment. Finally, a model is presented for the development of anti‐ADAMTS13 antibodies in previously healthy individuals that incorporates the recent identification of HLA DRB1*11 as a risk factor for acquired TTP.     

Amplified endogenous plasmin activity resolves acute thrombotic thrombocytopenic purpura in mice

Essentials

• Plasmin is able to proteolyse von Willebrand factor.
• It was unclear if plasmin influences acute thrombotic thrombocytopenic purpura (TTP).
• Plasmin levels are increased during acute TTP though suppressed via plasmin(ogen) inhibitors.
• Allowing amplified endogenous plasmin activity in mice results in resolution of TTP signs.

     

Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment

ABSTRACT

Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) is an immune-mediated deficiency in von Willebrand factor-cleaving protease ADAMTS13 allowing unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis. Caplacizumab, an anti-von Willebrand factor humanized, bivalent single-domain nanobody preventing its binding to the platelet has been investigated and approved for use in the treatment of iTTP.

Areas covered: The purpose of this article is to summarize the available clinical data on the efficacy and safety of caplacizumab in iTTP and to provide our opinion on the place of caplacizumab in current treatment regimens.

Expert opinion: Caplacizumab is a new drug with a complementary mechanism of action with respect to the standard available therapeutics. It demonstrated efficacy in clinical trials through a faster platelet count normalization and protection of patients from exacerbations and refractoriness. Caplacizumab is well tolerated with minor bleeds as the most important side effect. The efficacy of caplacizumab now needs to be assessed in real-life but definitely, this drug opens hope for a significant improvement in iTTP prognosis at the very early, critical step of the disease.

Trial registration: ClinicalTrials.gov identifier: NCT03922308.

Trial registration: ClinicalTrials.gov identifier: NCT02553317.