Effective and safe off-label use of caplacizumab treatment in a middle-aged obese male

This study shows clinical efficacy and safety profile of an off-label use of caplacizumab for the treatment of immune-mediated thrombotic thrombocytopenic purpura in a middle-aged obese male patient manifesting aphasia, weakness and unconsciousness. Routine blood tests revealed haemolytic anaemia, severe thrombocytopenia (platelet count = 20 × 10⁹/L) and moderate creatinine increase. Diagnosis was based on the clinical judgement and laboratory determinations (undetectable ADAMTS13 activity and presence of anti-ADAMTS13 antibodies). The patient underwent plasma-exchange and an adjunctive treatment with prednisone (1 mg/Kg/day), but the occurrence of a refractory and exacerbated form of disease suggested also using rituximab (375 mg/m² weekly for 4 weeks) and caplacizumab as salvage treatments. The caplacizumab was given at 10 mg/day subcutaneously without the first intravenous bolus. Because von Willebrand factor inhibition, platelet count recovery and remission of symptoms were achieved, use of caplacizumab with this scheme appeared to be as effective as the approved one. Although this is an off-label use, this case highlights the potential of this new treatment, in terms of drug's efficacy and safety.     

1例重症新型布尼亚病毒患者继发血栓性血小板减少性紫癜的护理

新型布尼亚病毒又称发热伴血小板减少综合征布尼亚病毒(severe fever with thrombocytopenia syndrome bunyavirus,SFTSV),是以发热伴血小板减少为主要特征的新型传染性疾病,临床表现主要为发热、血小板减少、白细胞减少及多器官功能损害[1]。每年4月至10月是新型布尼亚病毒的高发期。血栓性血小板减少性紫癜(thrombotic thrombocytopenic purpura,TTP)是一种严重的血栓性微血管病,临床表现为血小板减少、微血管病性溶血性贫血,以及神经系统损害、发热和肾损伤等。TTP的发生机制与严重的血管性血友病因子裂解酶(ADAMTS13)的活性降低密切相关,多数TTP患者起病急骤,病情凶险,如不及时救治,预后差,死亡率高达90%,血浆置换(plasma exchange,PE)是治疗TTP的首选疗法[2]。TTP患者通过PE去除血循环中抗ADAMTS13自身抗体,补充新鲜的ADAMTS13缺乏物质,可使患者病死率下降至8%~30%[3]。     

Evidence for a light chain restriction of glycoprotein Ib/IX and Ilb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP)

To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPHb/ Ilia-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IHa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes.     

Stenosing ureteritis in Henoch–Schönlein purpura: Report of two cases

Stenosing ureteritis (SU), a rare complication of Henoch–Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early‐stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non‐specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review.     

免疫性血小板减少性紫癜合并IgA肾病

目的：认识免疫性血小板减少性紫癜（ITP）合并IgA肾病这一新的临床病症，并对其可能的机制进行探讨。方法：回顾分析3例ITP合并IgA肾病患者的临床病理特征及治疗后的转归。结果：3例患者均经骨髓穿刺确诊为ITP，肾活检确认为IgA肾病。经激素等治疗后，ITP和IgA肾病均可得到缓解。结论：ITP可以合并IgA肾病。IgA肾病的发生可以继发于IPT，也不排除二者均源于骨髓干细胞功能异常的可能性。     

糖皮质激素治疗慢性特发性血小板减少性紫癜疗效相关因素分析

目的：探讨影响糖皮质激素治疗慢性特发性血小板减少性紫癜疗效的有关因素。方法：采用Logistic回归对74例经糖皮质激素治疗的慢性特发性血小板减少性紫癜患者性别、年龄、是否并发除皮肤出血以外较严重的出血表现、起病至开始治疗时间、是否有脾脏肿大、是否并发肝炎病毒感染、治疗前血小板计数、骨髓巨核细胞数8项因素进行多因素分析。结果：起病至开始治疗时间，是否并发肝炎病毒感染，骨髓巨核细胞数是影响糖皮质激素治疗慢性特发性血小板减少性紫癜疗效的相关因素。结论：分析患者治疗前各项可能影响疗效的相关因素，对于指导慢性特发性血小板减少性紫癜治疗方案的选择，尤其是合理掌握糖皮质激素的使用时间有重要意义。     

Chylothorax in Henoch-Schonlein purpura: a case report and review of the literature

Henoch-Schonlein purpura (HSP) is the most common acute vasculitis in the pediatric population, with an incidence of 10-14 per 100,000. The classic presentation of this disorder includes erythematous papules followed by palpable purpura in the lower extremities, trunk, and face, arthralgia or arthritis, abdominal pain, gastrointestinal bleeding, and nephritis. While renal abnormalities in HSP are common, the classic pulmonary manifestations, such as hemorrhage and pneumonitis, are thought to be infrequent. Subclinical pulmonary manifestations, including diffusion defects and radiographic anomalies, seem to be quite frequent in patients with HSP but are not commonly reported. Other respiratory manifestations include pleural effusion and chylothorax, but these are rarely mentioned in the literature. Chylothorax was only reported once in an adult patient with HSP in whom the mechanism of formation was demonstrated to be secondary to transdiaphragmatic passage of chylous fluid from the peritoneal cavity. Here we describe an 8-year-old girl with HSP, nephrotic syndrome, and chylothorax, and we report the results of a review of the literature regarding respiratory complications in HSP. The present case is the first pediatric patient reported with HSP and chylothorax. The therapeutic measures utilized were effective in resolving her edema, ascites, and chylothorax, and we advocate the use of these measures as first-line therapy in future patients with similar complications from HSP.     

尿微量蛋白和尿酶测定在过敏性紫癜患儿早期肾损伤中的临床意义

目的探讨尿微量清蛋白(MA)和尿酶测定在过敏性紫癜患儿早期肾损伤中的临床意义。方法选取120例过敏性紫癜患者作为研究组,过敏性紫癜患儿根据有无肾功损害分为早期肾损伤组和无损伤组,另选取同期该院行健康查体的40例健康儿童作为健康对照组,分析比较各组间尿MA和尿酶水平。结果研究组患者的MA为(17.5±3.8)mg/L、转铁蛋白(TRF)为(0.56±0.34)mg/L、β2-微球蛋白为(β2-MG)为(0.35±0.07)mg/L、N-乙酰-B-D-氨基-葡萄糖苷酶(NAG)为(18.6±5.1)U/L,显著高于健康对照组,差异有统计学意义(P0.05);早期肾损伤组MA(42.1±21.3)mg/L、TRF(1.65±0.54)mg/L、β2-MG(0.43±0.06)mg/L、NAG(23.1±5.12)U/L,显著高于无损伤组,差异有统计学意义(P0.05)。结论尿MA和尿酶检测可以作为监测过敏性紫癜患儿早期肾损伤的指标,有利于早期发现、及时干预,减少并发症的发生。     

幽门螺杆菌感染与儿童过敏性紫癜相关性的 Meta分析

目的：综合分析幽门螺杆菌（Hp）感染与儿童过敏性紫癜（HSP）的关系。方法通过检索 PubMed、Medline、Em‐base、万方数据库、中国期刊全文数据库（CNKI）、中国生物医学数据库（CBM ）及维普（VIP）等数据库,检索时间均为建库开始至2014年,全面收集公开发表的关于Hp感染与儿童 HSP关系的病例对照研究资料,采用 Meta分析方法对所有文献进行综合分析,并计算综合的优势比（odds ratio ,OR）值和95％可信区间（confidence interval ,CI）。结果共检索到相关文献68篇,最终纳入符合条件的文献13篇。结果显示,HSP组与对照组为：OR（95％ CI）为3.17（2.53～3.97）,合并效应量的检验结果Z＝10.06,P＜0.00001;腹型HSP与非腹型HSP组为：OR（95％ CI）为3.43（1.83～6.43）,合并效应量的检验结果Z＝3.85, P＝0.0001。结论 Hp感染与儿童 HSP的发病密切相关,尤其是腹型 HSP。