血栓性血小板减少性紫癜误诊1例

患者，女，19岁，因“发热、腹泻3d，伴牙龈出血、右肩右髋部出血点1d”，至我院急诊就诊。患者入院前3d无明显诱因出现腹泻、呕吐、高热、腹痛，腹泻初为水样便，量多，后逐渐为黑色便，发热体温最高达40℃。在家自服去痛片、阿莫西林、安乃近等药。入院前1d出现牙龈出血，伴右肩、右髋部出血点。来诊时急查化验示血常规：     

慢性特发性血小板减少性紫癜发病机制研究进展

特发性血小板减少性紫癜是一种异质性自身免疫性疾病，是儿童最常见的出血性疾病，尤其慢性患儿的健康相关生活质量受到严重影响，但其病因及发病机制目前仍不清楚。研究发现，遗传因素可能参与该病的发生及预后。该文从其危险因素、基因多态性和表达水平与其易患性及病情严重情况的关系、表观遗传的作用、慢性难治性特发性血小板减少性紫癜相关研究等方面作一综述。     

Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene

Upshaw–Schulman syndrome (USS) is due to severe congenital deficiency of von Willebrand factor (VWF)‐cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in the presence of unusually large forms of VWF in the circulation, causing intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26‐year‐old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the only sign of hemolytic activity. He had ADAMTS13 activity of <1% of normal plasma without the presence of inhibitors of ADAMTS13. ADAMTS13 deficiency was caused by two new mutations of the ADAMTS13 gene: a deletion of a single nucleotide in exon17 (c. 2042 delA) leading to a frameshift (K681C fs X16), and a missense mutation in exon 25 (c.3368G>A) leading to p.R1123H. This case report confirms the importance of the analysis of the ADAMTS13 activity and its inhibitor in patients who have episodes of TTP, with a very low platelet count and sometimes without the classic biochemical signs of hemolysis.     

Diagnosis and Management of Atypical Hemolytic Uremic Syndrome In Children: Single Centre Experience

Atypical hemolytic uremic syndrome (aHUS) although rare is the commonest cause of acute renal failure (ARF) in children and has poor prognosis. We present single centre experience of aHUS. Thirty six children (29 males, 7 females) with mean age, 7.9 years presented with ARF, 2 children also had tonic–clonic type convulsions. Their hematology examination revealed hemolytic anemia with s. creatinine (SCr), 5.54 mg/dl. Acute HUS was observed in 75 %, acute on chronic HUS in 19.4 % and patchy cortical necrosis (PCN) in 5.6 % biopsies. Mean 5.4 plasma exchanges (PE) were carried out. Supportive management of anti-hypertensives and prednisone was also given. Recovery end points were establishment of urine output, improvement of SCr and hematological profile. Hematology and renal function profile improved variably in all children, 5.6 % died, relapse was observed in 80.5 % over mean 70 days; 13.9 % children are doing well over mean follow-up of 268.8 days. Thus poor prognosis was observed in 86.1 % children. Children with acute on chronic HUS and PCN did not recover. Six children who recovered had acute HUS. aHUS in Indian children occurs at an older age of around 8 years and chronic/irreversible changes on histopathology examination are harbingers of poor prognosis. PE is life-saving however further research for developing strategies to improve long-term survival is needed.     

Acute pancreatitis induced thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown cause with an estimated incidence of one case per million. The disease is characterized by a pentad of symptoms: Thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, renal dysfunction, and fever. It causes thrombosis in the microvasculature of several organs, producing diverse manifestations. Acute pancreatitis (AP) is a well-described consequence of TTP. Acute pancreatitis triggering TTP is uncommon.     

小儿血液系统疾病人细小病毒B_(19)感染的研究

目的:探讨我国西北地区血液系统疾病患儿人细小病毒B19(HPV B19)感染情况及两者的相关性。方法:对特发性血小板减少性紫癜、再生障碍性贫血和白血病患儿的外周血分别采用PCR方法检测HPV B19-DNA和ELISA方法检测HPV B19-IgG。结果:特发性血小板减少性紫癜患儿HPV B19-IgG阳性率为43.08%(28/65),白血病患儿HPV B19-IgG阳性率为41.07%(46/112),病例组较对照组比较有极显著性差异(P<0.01);再生障碍性贫血患儿HPV B19-IgG阳性率为21.43%(6/28),病例组较对照组比较有显著性差异(P<0.05)。65例特发性血小板减少性紫癜患儿HPV B19-DNA阳性率为40.00%(26/65);28例再生障碍性贫血患儿HPV B19-DNA阳性率为21.43%(6/28);112例白血病患儿HPV B19-DNA阳性率为27.68%(31/112);对照组HPV B19-DNA检测均为阴性。结论:HPV B19感染与我国西北地区部分血液系统疾病患儿发病相关。     

Cellular expression of CD markers in immune thrombocytopenic purpura: implications for prognosis

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder associated with platelet destruction. Abnormalities in frequency and function of different immune cells can play a crucial role in this disease. The aim of this study was to evaluate the prognostic value of CD markers’ expressions by immune cells in ITP. Peripheral blood samples were collected from 25 ITP patients before and after treatment. The expression of CD markers was evaluated by flow cytometry technique. The expression of CD38 and CD56 was significantly lower before treatment than after it (p = 0.025 and p = 0.036, respectively). Furthermore, a positive correlation was found between CD38 expression with platelet count before (r = 0.496, p = 0.012) and after treatment (r = 0.404, p = 0.045). No significant relationship was found between this marker and platelet count while CD4 expression was higher before treatment than after it (p = 0.002). In conclusion, CD38 may have independent prognostic value in ITP and we suggest that it can be a prognostic marker for this disease.     

Multiple in silico tools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, recessively inherited genetic disorder with varying clinical presentation that is caused by ADAMTS13 mutations. Several studies have found limited associations between ADAMTS13 mutations and cTTP phenotype. The use of in silico tools that examine multiple mutation characteristics may better predict phenotype. We analysed 118 ADAMTS13 mutations found in 144 cTTP patients reported in the literature and examined associations of several mutation characteristics, including N‐terminal proximity, the evolutionary conservation of the affected amino acid position, as well as amino acid charge/phosphorylation and genetic codon usage to disease phenotype. Structure‐altering mutations were examined for their impact on ADAMTS13 function based on existing ADAMTS13 crystallographic data (AA 77‐685). Our in silico data indicate that: (i) The position of the mutation in the N‐ or C‐terminus, (ii) evolutionary conservation and (iii) codon usage of the affected mutation position are associated with disease parameters, such as age of onset, organ damage and fresh frozen plasma prophylaxis. In conclusion, the usage of multiple in silico tools presents a promising strategy in refining predictions for the diverse presentation of cTTP. Enhancing our utilization of in silico tools to find genotype‐phenotype associations will create better‐tailored approaches for individual patient treatment.     

Familial acquired thrombotic thrombocytopenic purpura in siblings – no immunogenetic link with associated human leucocyte antigens

Acquired immunoglobulin G (IgG)‐mediated thrombotic thrombocytopenic purpura (TTP) has not yet been described in non‐twin siblings. We report two cases of acquired TTP in Caucasian sisters with inactive ADAMTS13 metalloprotease due to ADAMTS13 autoantibodies suggesting a role of genetic determinants in this life‐threatening disease. However, human leucocyte antigen (HLA) class II types presumably associated with acquired TTP were not identified in the patients, indicating that HLA class II typing may not be useful in acquired TTP risk assessment of family members.