婴儿遗传性血栓性血小板减少性紫癜1例报告

目的探讨遗传性血栓性血小板减少性紫癜(TTP)的诊断及治疗。方法回顾分析1例遗传性TTP患儿的临床资料。结果女性患儿,出生后不久即出现黄疸、易激惹、贫血、血小板减少、蛋白尿,并反复发作。基因测序显示,ADAMTS 13基因外显子2个杂合突变,c. 3616 CT(胞嘧啶胸腺嘧啶)、c. 334 delG缺失突变,分别来自于父母,属于复合杂合突变,符合常染色体隐性遗传规律。明确诊断为血栓性微血管病中的遗传性TTP。患儿先后多次复发,经输注血浆治疗效果好。结论临床上典型或不典型溶血性贫血,同时伴血小板减少、肾损害等应警惕遗传性TTP,基因检测有助诊断。遗传性TTP可输注血浆治疗。     

儿童血栓性血小板减少性紫癜

血栓性血小板减少性紫癜（TTP）在儿童病例中甚为少见,但如未能及时诊断及施予治疗,其后果则极为严重。其最常见之5种病症为：血小板减少、微血管溶血性贫血、急性肾衰竭、发热及中枢神经系统症状。但临床病例中,并不一定会同时出现上述5种症状。故此医疗人员对此病必须有极高之警觉性。TTP之病理特征包括：外周血涂片可见裂体细胞,Coombs 试验阴性,血清乳酸脱氢酶增高及中度或重度血小板减少。TTP发病机理主因缺乏ADAMTS13,从而引发微血管溶血性贫血及血小板减少。TTP可概括分为家族性TTP（Upshaw Schulman 综合征）和继发性TTP。家族性TTP是由于先天性ADAMTS13缺乏所致,其急性治疗法为血浆置换,当病情稳定后,可输注新鲜冰冻血浆以防止病情复发。继发性TTP是指患者因体内产生抗体而导致ADAMTS13功能减退,主要治疗方法亦为血浆置换,最新之临床文献显示rituxiamb对此症亦颇有治疗价值。     

儿童获得性血栓性血小板减少性紫癜五例分析

目的:探讨儿童获得性血栓性血小板减少性紫癜(aTTP)的临床特点、治疗情况以及预后。方法:回顾性病例总结,以2016年1月至2019年7月于首都医科大学附属北京儿童医院住院治疗的5例aTTP患儿为研究对象,分析患儿临床表现、实验室检查、治疗及预后情况。结果:纳入5例aTTP患儿,占同期血栓性血小板减少性紫癜患儿的5/11,其中男2例、女3例,发病年龄8.9(0.8~14.5)岁。5例患儿均存在血小板减少和微血管病性溶血性贫血,仅1例存在经典五联征,3例患儿伴神经系统症状,3例有发热,而肾功能损伤相对少见(1例)。5例患儿均存在重度血小板减低[7(4~14)×10⁹/L]及血红蛋白下降[70(58~100)g/L];血生化检查示3例总胆红素水平升高,均以间接胆红素升高为主,5例乳酸脱氢酶水平均升高,1例尿素氮升高。骨髓穿刺提示巨核细胞数目不低。ADAMTS13活性检查均为0,4例ADAMTS13抑制物阳性,1例为阴性。5例患儿均接受糖皮质激素治疗,并且在疾病早期应用利妥昔单抗治疗,3例患儿接受血浆置换。5例患儿血小板恢复正常的时间为开始治疗后的19(9~29)d。1例患儿在治疗9个月后出现复发,再次予糖皮质激素及利妥昔单抗治疗后病情稳定,随访3年以上确诊为系统性红斑狼疮。截至2020年12月1日,随访24(16~57)个月,5例患儿临床症状消失,未次随访血小板计数为159(125~269)×10⁹/L。结论:儿童aTTP患者较为少见,各年龄段均有发病,临床表现以血小板减少及微血管病性溶血为主,血浆ADAMTS13活性及抑制物检测有助于aTTP的诊断。血浆置换及利妥昔单抗治疗有效,该病需长期随诊监测。     

2日龄新生儿高胆红素血症合并血小板减少

患儿,女,生后2 d,因皮肤巩膜黄染半天入院。主要临床表现为持续严重的黄疸和血小板减少,最终确诊为先天性血小板减少性紫癜（TTP）。先后予光疗、输注新鲜冰冻血浆、红细胞、血小板及换血等治疗后,患儿病情好转。基因检测结果提示患儿ADAMTS13基因存在c.3650T > C (p.I1217T)纯合突变,其父母该位点均为杂合突变。先天性TTP是一种罕见的常染色体隐性遗传疾病,及时输注新鲜冰冻血浆可获得良好疗效。该病例为国内外首例报道该位点纯合突变所致的先天性TTP患儿。     

特发性血小板减少性紫癜及再生障碍性贫血患儿血清血小板生成素的测定

研究特发性血小板减少性紫癜及再生障碍性贫血患儿血清血小板生成素水平变化及其临床意义 ,采用放射免疫法检测 1 5例特发性血小板减少性紫癜患儿、9例再生障碍性贫血患儿和 1 3例正常儿童血清血小板生成素水平。结果显示 ,特发性血小板减少性紫癜患儿血清血小板生成素水平为 ( 1 0 0 0 8± 38 4 )pq ml,与正常对照组无显著差异 (P >0 0 5) ,再生障碍性贫血患儿血清血小板生成素水平为 ( 1 4 4 0 7±2 83)pq ml,显著高于正常儿 (P <0 0 5)。因此 ,儿童特发性血小板减少性紫癜血清血小板生成素水平受骨髓巨核细胞数调控 ,外周血血小板数量则是再生障碍性贫血患儿血清血小板生成素水平的主要调节因素。     

血小板特异性抗体的测定与特发性血小板减少性紫癜的关系

特发性血小板减少性紫癜 (ＩＴＰ)发生的主要原因是抗血小板自身抗体引起的血小板破坏 ,因而血小板自身抗体的检测对ＩＴＰ的诊断及发病机理的研究有重要价值。本研究用改良的血小板抗原单抗特异性固相化法 (ｍｏｎｏｃｌｏｎａｌａｎｔｉｂｏｄｙｓｐｅｃｉｆｉｃｉｍｍｏｂｏｌｉｚａｔｉｏｎｏｆｐｌａｔｅｌｅｔａｎｔｉｇｅｎｓ ,ＭＡＩＰＡ)测定了ＩＴＰ患儿和非免疫性血小板减少症患儿血清中的抗ＧＰＩＩｂ/ＩＩＩａ和抗ＧＰＩｂ/Ｉｘ自身抗体 ,并同时测定这些患儿的血小板表面相关抗体 (ＰＡＩｇＧ) ,将二者作比较 ,试图评价血小板…     

以血小板减少性紫癜为首发表现的儿童系统性红斑狼疮13例诊治分析

目的 总结儿童系统性红斑狼疮的诊治经验.方法 回顾性分析2004年1月至2009年6月我院收治的13例以急性免疫性血小板减少性紫癜为首发症状的小儿系统性红斑狼疮的诊断、治疗及转归情况.结果 13例初诊患儿经临床表现及骨髓检查诊断为急性免疫性血小板减少性紫癜,经用激素及静脉丙种球蛋白治疗效果欠佳,动态随诊免疫指标及其他临床表现,并根据血液系统改变特点和对激素的反应加用其他免疫抑制剂如环孢素A、霉酚酸酯及环磷酰胺等.13例患儿分别于2～24个月确诊为系统性红斑狼疮,加用其他免疫抑制剂后治疗效果满意.结论 对于血小板减少的患儿尤其是青春期女孩要注意动态监测抗核抗体及其他免疫学指标,警惕系统性红斑狼疮的可能.     

特发性血小板减少性紫癜患儿血小板生成素及其受体基因转录水 …

目的 探讨急性特发性血小板减少性减少性紫癜（ＡＴＴＰ）患儿血小板生成素（ＴＰＯ）及血小板ＴＰＯ受体ｃ－ＭＰＬ ｍＲＮＡ基因转化水平变化的意义。方法 采用ＥＬＩＳＡ法检测血清ＴＰＯ、血小板相关抗体（ＰＡＩｇＧ）水平;半定量ＲＴ－ＰＣＲ法检测外周血血小板ｃ－ＭＰＬ ｍＲＮＡ的相对量。结果 ＡＴＴＰ患儿初治时血浆ＴＰＯ水平增高,血小板ｃ－ＭＯＬ ｍＲＮＡ较低;以大剂量甲基强的松龙冲击治疗后,位随血小板计     

血细胞减少患儿血液标本中人微小病毒B19—DNA的检测

人微小病毒Ｂ１９（ＨＰＶＢ１９）可引起再生障碍性贫血，有时也可引起粒细胞减少、血小板减少及纯红细胞再生障碍性贫血。在接受化疗的患儿严重贫血时，也发现有ＨＰＶＢ１９病毒血症。我们用ＰＣＲ技术对１９９３年１１月－１９９５年２月间２０例血细胞减少和３０例过敏性紫癜患儿的血清标本作了ＨＰＶＢ１９－ＤＮＡ检测，其中血小板减少９例，白血病４例，自身免疫性溶血性贫血２例，再生障碍性贫血２例，纯红细胞再生障碍性贫     

特发性血小板减少性紫癜患儿血小板膜糖蛋白特异性抗体水平检测的意义

目的检测特发性血小板减少性紫癜（ITP）与非免疫性血小板减少症（Non-ITP）患儿血浆中血小板膜糖蛋白特异性抗体,评价该法在ITP与Non-ITP患儿中的诊断与鉴别诊断的价值。方法用改良单克隆抗体特异性俘获血小板抗原技术,检测ITP与Non-ITP患儿抗血小板GPⅡbⅢ/a和抗GPⅠbⅨ/的特异性抗体;酶联免疫吸附竞争法检测其血小板相关抗体（PAIgG）,对二种方法所测结果进行比较。结果ITP患儿血浆中抗GPⅡbⅢ/a的特异性抗体阳性率为47.4%,抗GPⅠbⅨ/的特异性抗体阳性率为22.8%,抗GPⅡbⅢ/a和抗GPⅠbⅨ/同时阳性为15.8%,总阳性率54.4%,且多数为GPⅡbⅢ/a抗体;其中,慢性ITP患儿血浆中抗GPⅡbⅢ/a和抗GPⅠbⅨ/特异性抗体总阳性率为66.7%,略高于急性ITP患儿;Non-ITP患儿血浆中仅抗GPⅡbⅢ/a抗体阳性率为20.0%,抗GPⅠbⅨ/抗体未检出,与ITP比较有显著性差异（P〈0.01）;PAIgG检测ITP患儿阳性率为84.2%,Non-ITP患儿阳性率为75.0%,二者比较无显著性差异（P〉0.05）;特异性抗体检测诊断ITP的灵敏度为54.4%,特异度为80.0%,阳性预测值为88.6%。结论抗血小板特异性抗体检测对于鉴别诊断ITP与Non-ITP有一定的临床意义。     

Thrombocytopenia and severe hyperbilirubinemia in the neonatal period secondary to congenital thrombotic thrombocytopenic purpura and ADAMTS13 deficiency

Congenital thrombotic thrombocytopenic purpura (TTP) is an inherited form of TTP due to the deficiency of von Willebrand factor (vWF) cleaving protease ADAMTS13. The authors describe two children with congenital TTP who presented with thrombocytopenia, hemolytic anemia, elevated LDH levels, and schistocytes on peripheral blood smear. In both children, the diagnosis of the disease was delayed despite neonatal histories significant for thrombocytopenia, anemia, and severe hyperbilirubinemia. Severely decreased ADAMTS13 activity (<0.1 U/mL), the absence of an inhibitor to the protease, and partial deficiency found in the parents confirmed the diagnosis of congenital TTP. The authors suggest that congenital TTP should be considered in the differential diagnosis for newborns presenting with severe hyperbilirubinemia, anemia, and thrombocytopenia.     

Mikroangiopatie zakrzepowe: nowe spojrzenie na patofizjologię i terapię

Thrombotic microangiopathy (TMA) is defined as process of endothelial cell damage, affecting mainly arterioles and capillaries, resulting in intraluminal thrombosis, platelet clumping, microangiopathic hemolytic anemia and occlusion of the vessel lumen. TMA encompasses hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP), differentiated mainly by microbiologic tests and activity of protein ADAMTS13. Currently, four types of hemolytic uremic syndrome are distinguished: typical, atypical, secondary and idiopathic. Typical HUS is caused by bacterial toxins, mainly Shiga toxin-producing Escherichia coli (STEC-HUS). Atypical HUS develops as a result of pathologic activation of alternative complement pathway, mainly as a genetic defect. Secondary HUS includes various diseases with underlying pathophysiology causing development of microangiopathy. Idiopathic HUS is diagnosed after exclusion of other thrombotic microangiopathies and genetic defects. Thrombotic thrombocytopenic purpura results after decrease of activity of metalloproteinase ADAMTS13, which physiologically cleaves multimers of von Willebrand factor to subunits with lower procoagulation activity. ADAMTS13 deficiency can be congenital or acquired. Inherited forms are based on recessive mutations of ADAMTS13 gene. Acquired TTP are of immunological character, and appears with autoantibodies against ADAMTS13 protein. The predisposing factor for these antibodies is presence of HLA-DRB1*11 antigen. This review presents current knowledge on definitions, pathophysiology, differential diagnostics and therapy of thrombotic microangiopathies. A new perspective on targeted therapy in hemolytic uremic syndrome, based on the use of eculizumab, monoclonal antibody against C5 protein of complement pathway, is underlined.     

Thrombotic thrombocytopenic purpura in a newborn]

A newborn presented with haemolytic anemia, thrombocytopenia, hyperbilirubinemia and renal failure as early as the first hours of life. An early plasmatherapy was undertaken, followed by good outcome. The specific von Willebrand factor-cleaving protease (ADAMTS 13) was found at less than 5%. This is the specific biologic diagnostic element of congenital thrombotic thrombocytopenic purpura or Upshaw-Schulman syndrome. This disease of constitutional thrombotic microangiopathy was well identified and understood only few years ago. It's a rare disease which early diagnosis and treatment are crucial in order to preserve functional and vital capacities of the patient.     

Coombs Positive Thrombotic Thrombocytopenic Purpura in a Male Pediatric Patient: An Urgent Diagnostic Challenge

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy often caused by deficiency of von Willebrand (vW) factor cleaving protease, ADAMTS‐13, leading to large vW multimers and intravascular platelet aggregation. Hemolysis in TTP is mechanical and nonimmune mediated, thus Coombs testing is usually negative. We report a case of an adolescent with thrombocytopenia and Coombs positive anemia, diagnosed with Evans syndrome, but ultimately found to have TTP. TTP should be considered in children with thrombocytopenia and Coombs positive anemia who are refractory to steroids or develop signs of microangiopathy.  Recognition of this presentation can lead to life‐saving treatment with plasma exchange.     

Chronic relapsing thrombotic thrombocytopenic purpura in infants with large von Willebrand factor multimers during remission.

We studied two children with recurrent schistocytic hemolytic anemia and thrombocytopenia beginning in the neonatal period. One patient had a stroke during one of the episodes of thrombotic thrombocytopenic purpura. The presence of unusually large von Willebrand factor multimers was demonstrated in both children during clinical and hematologic remissions. Treatment with corticosteroids and intravenous injections of immune globulin was unsuccessful in the one patient who received it. Immediate improvement occurred in both patients after the infusion of fresh-frozen plasma. Symptoms of thrombocytopenia continue to recur at regular intervals in the absence of periodic fresh-frozen plasma infusions. One of these children apparently has chronic relapsing thrombotic thrombocytopenic purpura; the second has a chronic relapsing disorder similar to thrombotic thrombocytopenic purpura.     

Severe vitamin B-12 deficiency in a child mimicking thrombotic thrombocytopenic purpura

We report a case of severe vitamin B-12 deficiency in a child who had a clinical presentation of hemolysis and thrombocytopenia that suggested the diagnosis of thrombotic thrombocytopenic purpura (TTP) and was associated with decreased ADAMTS13 activity. In this report, we review vitamin B-12 deficiency in children, the relationship between ADAMTS13 activity and TTP and discuss other conditions associated with decreased ADAMTS13 activity.     

Thrombotic microangiopathy and Purtscher-like retinopathy as a rare presentation of juvenile dermatomyositis

Juvenile dermatomyositis is a rare systemic vasculopathy that may sometimes present with acute complications. We report here the case of a 7-year-old boy with severe dermatomyositis associated with thrombocytopenia and blurry vision. The presence of schistocytosis and the secondary occurrence of hemolytic anemia were consistent with a diagnosis of thrombotic thrombocytopenic purpura (TTP). Further investigations demonstrated the association of TTP with muscular microangiopathy and Purtscher-like retinopathy. Retinal and hematologic involvements dramatically improved after the initiation of plasma exchange in emergency. This report emphasizes that early recognition of TTP and prompt plasmapheresis are important in a child with severe juvenile dermatomyositis associated with thrombocytopenia.     

儿童继发性血栓性血小板减少性紫癜1例并文献复习

目的 提高对儿童不典型继发性血栓性PLT减少性紫癜（TTP）的认识。 方法 总结1例无神经系统受累的继发性TTP患儿的临床资料、实验室检查结果、ADAMTS13酶活性和Anti-ADAMTS13抗体检测结果,行系统文献检索并文献复习。 结果 男性患儿,12岁,急性起病,病初有发热,双下肢可见瘀点,PLT及Hb进行下降,血涂片可见破碎RBC,高胆红素血症,LDH明显升高,镜下血尿,肾功能正常,补体正常,考虑血栓性微血管病(TTP或非典型溶血尿毒综合征)。为进一步明确诊断, 行ADAMTS13酶活性检测2.3%（正常值40％~130%）,ADAMTS13抗体检测90 U·mL-1（正常值＜12 U·mL-1）,确诊继发性TTP,予血浆置换和激素治疗。4个月后患儿停用所有药物,目前停药6月无复发。系统检索中国知网、万方和PubMed数据库,共有14篇英文文献中40例继发性TTP进入本文分析,发病年龄（10.2±5.2）岁,男19例,女21例,发热36例（90%）,神经系统受累28例（70%）,肾脏受累18例（45%）,均有贫血和PLT降低。3例死亡,37例血浆置换+激素治疗,31例（83.8%）对血浆置换治疗即时反应好,1例因血浆过敏和1例血浆置换导管相关感染改为激素+利妥昔单抗治疗反应好,1例难治性继发性TTP加长春新碱（利妥昔单抗上市前）随访时复发,2例发生血浆置换依赖,加环孢素后治疗反应好,1例治疗反应不好,加长春新碱后治疗反应好,,4例失访（10.8%）,平均随访时间29月（3~72个月）,13例（39.4%）出现复发,9/13例加利妥昔单抗中仍有2例复发。 结论 贫血和PLT降低应怀疑TTP,需行ADAMTS13酶活性及其抗体的检测,有助于区别遗传性和获得性TTP;血浆置换+激素,或+利妥昔单抗是TTP的治疗组合选项。     

Remission of thrombotic thrombocytopenic purpura in a patient with compound heterozygous deficiency of von Willebrand factor-cleaving protease by infusion of solvent/detergent plasma

Plasma exchange or plasma infusion is considered to be the therapy of choice in patients with thrombotic thrombocytopenic purpura (TTP) who are deficient in von Willebrand factor-cleaving protease (VWF-CP). Recently, mutations in the ADAMTS 13 gene were identified as being responsible for VWF-CP deficiency in patients with familial TTP (VWF-CP deficiency in the absence of an inhibitor). Here we report on a girl who presented with recurrent thrombocytopenia and anaemia since birth, developing the full pentad of characteristic TTP at the age of 16 y. Congenital TTP was confirmed on the basis of severe VWF-CP deficiency in the absence of an acquired inhibitor. The patient was found to be compound heterozygous for two hitherto undescribed mutations in the ADAMTS 13 gene: a truncating frame shift mutation, 4143insA in exon 29, and the nonsense mutation 3100A >T in exon 24 (R1034X). After infusion of solvent/detergent plasma, the patient went into remission and remained asymptomatic under regular plasma therapy at 2-wk intervals for over two years. Conclusion: TTP in childhood may be mild and oligosymptomatic. Determination of VWF-CP activity is helpful in the differential diagnosis of thrombocytopenia.