Giant platelet disorders in African-American children misdiagnosed as idiopathic thrombocytopenic purpura.

A retrospective chart review of six African-American children with a diagnosis of macrothrombocytopenias (MTCP) was performed to evaluate the accuracy of their diagnosis. The following was diagnosed in the six children with MTCP: Fechtner syndrome (two children), Sebastian syndrome (one child), and unnamed MTCP (three children). In five families, chronic idiopathic thrombocytopenic purpura (ITP) was diagnosed in the propositus, which resulted in therapy using steroids, intravenous immunoglobulin (IVIG), and in one case splenectomy. Bleeding symptoms were generally mild. All six patients had thrombocytopenia ranging from 10 to 125 x 10(9)/L with mean platelet volume of 8 to 20 fL. Bleeding times were abnormal in two of three patients, and platelet aggregation was abnormal in three of four patients tested. Bone marrow aspirates were reported as increased megakaryocytes in the three patients on whom the procedure was performed. Ultrastructural morphology of platelets and leukocytes was performed in all six patients demonstrating giant platelets in all six patients and leukocyte inclusions in three patients. Differentiating MTCP from the more common ITP can be difficult but important in avoiding unnecessary diagnostic studies and potentially harmful therapy associated with ITP.     

Idiopathic thrombocytopenic purpura: a 10-year natural history study at the childrens hospital of alabama

Childhood idiopathic thrombocytopenic purpura (ITP) is a common disorder. However, single-institution, long-term, natural history data are limited. The objective of this paper is to review presenting features, response to therapy, and natural history of ITP treated at a single pediatric academic medical center. A retrospective chart review was made for all children (ages birth-18 years) diagnosed with ITP (ICD 287.3) and treated at the Childrens Hospital of Alabama/University of Alabama at Birmingham between 1993 and 2003. Four hundred nine patients were identified (49% male, 51% female; mean age: 5.85 years; range: 1 month-17 years). There was no seasonal variation of presentation. The mean platelet count was 19k (0-120k). Bone marrow aspiration (BMA) was performed in 72% but altered the diagnosis or therapy in no patient. Treatment consisted of corticosteroids in 256 (92% response), intravenous immunoglobulin (IVIG) in 125 (87% response), Win-Rho D in 58 (91% response), and no therapy in 71 (100% response). Response was defined as increase in platelet count to > 50k. There was no difference in response to any therapy. No patients died. One patient presented with a CNS hemorrhage at presentation, responded to therapy, and survived. Twenty-three of 409 patients (6%) experienced clinical bleeding requiring hospitalization or blood transfusion. Chronic ITP (persistence > 6 months) was noted in 99 patients (24%). Chronic patients presented at an older age (7.8 vs 5.2 years for acute only, p<0.001), and with higher platelet counts (27k vs 17k, p<0.001). The risk of chronic ITP was partially predicted by presenting platelet count > 50k and age > 10 years, or both; 50% of patients presenting with these features developed chronic ITP vs 24% overall rate. Splenectomy was curative in 30/31 (97%) patients. There was no postsplenectomy sepsis. Of 99 patients with chronic ITP, 25 responded to splenectomy, 37 resolved at a mean of 20.3 months after diagnosis (7-96 months), 36 had persistent mild thrombocytopenia (50k-125k), and 1 failed to respond to any treatment including splenectomy. Overall, 91% of cases resolved with therapy or observation. ITP is a common pediatric disease presenting at any age with low morbidity and mortality. Most cases can be managed by pediatricians without hematology referral. Several equally successful therapeutic options exist. Chronic cases present at an older age with higher platelet counts. Up to 50% of cases of chronic ITP will resolve with ongoing follow-up. The overall prognosis in childhood ITP is excellent.     

Main causes of aplastic anemia misdiagnosed as immune thrombocytopenia in children北大核心CSCD

目的归纳曾被误诊为免疫性血小板减少症(ITP)的50例儿童再生障碍性贫血(再障)的主要原因和鉴别诊断经验,以供临床参考。方法参照儿童再障和ITP诊断标准,回顾性分析2007年1月至2020年12月上海市同济医院儿科收治的外院误诊病例的病初资料和本院复诊检测结果,归纳误诊原因和鉴别诊断要点。结果在同期收治的165例儿童再障中,共有50例(30.3%)曾被误诊为ITP。分析归纳主要误诊原因为:1.临床表现不符合"典型ITP",未按照国际指南标准行必要的骨髓检查以明确诊断,共22/50例。2.骨髓检测结果解读有误。在28例初诊行骨髓涂片检查者中,6例(21%)骨髓显示典型再障骨髓象,但仍被诊断为ITP。3.骨髓涂片结果不典型者,未行骨髓活检以助诊断(15/28例,54%)。4.初诊时符合ITP诊断标准,但经糖皮质激素等治疗无效后,未行必要复查以核实诊断(7/28例,25%)。结论临床应严格参照执行相关疾病诊断标准,以避免经验性错误。诊断ITP需要慎重,尤其是临床表现不典型,或一线药物无效者,必须进行骨髓检查(必要时行骨髓活检),并按诊断标准正确解读检测结果,以避免临床误诊或漏诊。     

The management of immune thrombocytopenic purpura

The most common cause of thrombocytopenia in childhood is immune. The diagnosis must be carefully considered, as there are no specific diagnostic tests. Most children have an acute disease with spontaneous remission within a few weeks. Although the platelet count may be very low, bleeding symptoms are rarely severe, and most often restricted to the skin and mucous membranes. Most children do not require active treatment, but can be managed with good advice, ongoing support and a 24-h contact point. Children with significant bleeding problems may be treated with oral steroids, reserving intravenous immunoglobulin for emergencies or to cover injuries and surgery. About 20% of children continue with thrombocytopenia beyond 6 months (chronic ITP), but expectant management can continue, treatment is rarely required. Splenectomy is rarely required and should be reserved for the very rare child with serious bleeding persisting beyond 6 or 12 months.     

Isolated thrombocytopenia in children: thinking beyond idiopathic thrombocytopenic purpura and leukaemia

The commonest cause of isolated thrombocytopenia in an otherwise well child is idiopathic thrombocytopenic purpura (ITP). The inherited thrombocytopenias such as Bernard-Soulier syndrome are rare but often misdiagnosed as ITP owing to a similar clinical presentation. We describe a child with Bernard-Soulier syndrome who presented with isolated thrombocytopenia, mimicking ITP. Features which help to differentiate these two conditions are discussed with a brief literature review.     

Virus-associated immune thrombocytopenic purpura in childhood

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immunodeficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, Ihsan Dogramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELlSA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.     

Factors associated with delay in diagnosis of childhood amblyopia

The prevention of permanent visual impairment from amblyopia is an important goal of pediatric vision screening. Unfortunately, many cases of amblyopia are not diagnosed until the child is too old to benefit maximally from treatment. A review of patient records from the practice of a private pediatric ophthalmologist confirmed that late detection is a frequent occurrence among children with amblyopia who have had good access to health care. A case-control study was then used to identify factors associated with delayed diagnosis, in which children with an adverse outcome (diagnosed at or after 5 years of age) were compared with those with an optimal outcome (diagnosed before 5 years of age). The chart review identified 161 children with amblyopia who participated in this study; 75 had late diagnoses (case patients) and 86 served as control patients. Children with early diagnoses more often had the following characteristics: a positive family history of strabismus, greater degrees of strabismus (when strabismus was present), higher maternal educational level, greater parental suspicion that an eye problem existed, and an increased chance that the parents requested the eye examination that led to the diagnosis. The parents of children with late diagnoses expressed less concern over the seriousness of amblyopia but were more likely to report that their children had suffered adverse consequences of amblyopia. When diagnosed early, amblyopia was more often detected by the child's primary health care provider. Physicians of the children with early diagnoses more often reported compliance with both the American Academy of Pediatrics guidelines for vision screening in infancy and referral for vision problems.(ABSTRACT TRUNCATED AT 250 WORDS)     

NK细胞在儿童免疫性血小板减少症发病和治疗中的意义

目的：探讨自然杀伤细胞（NK细胞）在儿童免疫性血小板减少症（ITP）的发病和治疗中的意义。方法采用流式细胞仪分别检测62例新诊断ITP患儿、43例持续性ITP患儿、21例慢性ITP患儿和51例对照组儿童外周血NK细胞百分比;并观察单独使用标准剂量静脉注射用人免疫球蛋白（IVIG）对NK细胞百分比正常及减少的新诊断的ITP患儿的疗效。结果新诊断ITP患儿、持续性ITP、慢性ITP患儿NK细胞百分比均较正常对照组儿童显著降低（P＜0.05）,但三组ITP患儿NK细胞百分比差异无显著性（P ！0．05）;NK细胞百分比正常的新诊断ITP患儿单独使用IVIG有效率为92．86％（26/28）,NK细胞百分比降低的新诊断ITP患儿单独使用IVIG有效率仅为14．70％（5/34）。结论 NK细胞表达变化与ITP发病存在一定关系,同时NK细胞百分比正常的新诊断ITP患儿可首选IVIG治疗。     

VIRUS-ASSOCIATED IMMUNE THROMBOCYTOPENIC PURPURA IN CHILDHOOD

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immuno deficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, &#71 hsan Do &#60 ramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELISA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.     

Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: A prospective Nordic study of an unselected cohort

OBJECTIVE: To determine the duration of the risk period with platelet counts <20 x 10(9)/L and the frequency of bleeding episodes in unselected children with idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: We established a registry for patients with newly diagnosed ITP in the five Nordic countries, enrolling children aged 0 to 14 years with platelet counts <30 x 10(9)/L. Treatment centers prospectively reported presenting features, management details, and disease-related events during the first six months after diagnosis. RESULTS: At presentation (n=501), more than half of the children had a platelet count <10 x 10(9)/L, but only 15 (3.0%) had a hemorrhage requiring blood transfusion. During follow-up of 409 patients, thrombocytopenia resolved uneventfully in 277. A risk period was present in 376 cases. Among 283 with self-limiting ITP, 26 were at risk >1 month and 25 had 30 events. Among 93 patients with chronic ITP, 73 were at risk >1 month and 44 had 111 events. Events occurred with an average frequency of 0.39 per month at risk. Life-threatening hemorrhages did not occur in the first six months after diagnosis. CONCLUSION: Most children with ITP are at risk for serious bleeding for less than one month. Continuing severe thrombocytopenia is associated with little morbidity, bleeding episodes being infrequent and very rarely serious.     

Thrombocytopenic Purpura and Coeliac Disease

ABSTRACT. In a child with immune thrombocytopenic purpura (ITP) the findings of circulating reticulin antibodies and IgA and IgG gliadin antibodies suggested the diagnosis of coeliac disease. This was verified by small intestinal biopsy. In spite of a gluten-free diet the thrombocytopenia persisted. The association of ITP and coeliac disease was previously described in adults but to our knowledge this is the first report of the coexistence of ITP and coeliac disease in a child.     

Thrombocytopenic purpura and coeliac disease

In a child with immune thrombocytopenic purpura (ITP) the findings of circulating reticulin antibodies and IgA and IgG gliadin antibodies suggested the diagnosis of coeliac disease. This was verified by small intestinal biopsy. In spite of a gluten-free diet the thrombocytopenia persisted. The association of ITP and coeliac disease was previously described in adults but to our knowledge this is the first report of the coexistence of ITP and coeliac disease in a child.     

Use of romiplostim for primary immune thrombocytopenia in children

Very little has been published on the use of romiplostim to treat primary immune thrombocytopenia (ITP), refractory to previous treatments, in children. The objective of this study was to determine its efficacy and safety in pediatric patients in a university general hospital. Retrospective, longitudinal observational study of pediatric patients on treatment with romiplostim. The principal efficacy variable was platelet count. Safety was evaluated by recording possible adverse reactions to the medication, monitoring the appearance of thrombosis, thrombocytopenia during dose reduction, hemorrhage, and myelodysplastic syndromes. Three patients in the authors' center have been treated with romiplostim (subcutaneous [SC], initial dose: 1 μg/kg/week) for ITP refractory to various treatments: 1 with newly diagnosed ITP and 2 with chronic ITP. Patients were followed up for 27 to 39 weeks after starting treatment. Responses were achieved in 7 to 28 days, and complete responses were maintained for 37% to 91% of the follow-up period, with median platelet counts between 40 × 10(3)/μL and 215 × 10(3)/μL. The adverse reactions observed during follow-up were headache and asthenia in one patient and mucocutaneous bleeding after dose suspension in another one. With regard to effectiveness, the response in the 3 patients was varied. The drug was considered to be safe, as there were only mild adverse reactions. Although further studies and long-term follow-up are required, these results show that romiplostim could be considered an alternative to immunosuppressive therapies, such as rituximab, or splenectomy in refractory chronic ITP.     

Thrombocytopenia and thromboembolism in pediatric systemic lupus erythematosus

To define in children with systemic lupus erythematosus (SLE) the incidence, outcome, and association of thrombocytopenia with other SLE manifestations, specifically thromboembolic events (TEs), we retrospectively reviewed 106 pediatric patients with SLE diagnosed between 1992 and 2001. Thrombocytopenia was found in 50%, which was of a moderate or severe degree in 34%. The thrombocytopenia was sustained in 29% of all patients. Twelve patients were diagnosed with autoimmune thrombocytopenic purpura 2 to 69 months before the diagnosis of SLE. Of them, 10 children required treatment, and three patients underwent splenectomy. TEs occurred in 10.4% of the total cohort of 106. Lupus anticoagulant, but not anticardiolipin antibodies and sustained thrombocytopenia, were associated with a higher risk for TEs.     

Use of Romiplostim for Primary Immune Thrombocytopenia in Children

Very little has been published on the use of romiplostim to treat primary immune thrombocytopenia (ITP), refractory to previous treatments, in children. The objective of this study was to determine its efficacy and safety in pediatric patients in a university general hospital. Retrospective, longitudinal observational study of pediatric patients on treatment with romiplostim. The principal efficacy variable was platelet count. Safety was evaluated by recording possible adverse reactions to the medication, monitoring the appearance of thrombosis, thrombocytopenia during dose reduction, hemorrhage, and myelodysplastic syndromes. Three patients in the authors’ center have been treated with romiplostim (subcutaneous [SC], initial dose: 1 μg/kg/week) for ITP refractory to various treatments: 1 with newly diagnosed ITP and 2 with chronic ITP. Patients were followed up for 27 to 39 weeks after starting treatment. Responses were achieved in 7 to 28 days, and complete responses were maintained for 37% to 91% of the follow-up period, with median platelet counts between 40 × 10³/μL and 215 × 10³/μL. The adverse reactions observed during follow-up were headache and asthenia in one patient and mucocutaneous bleeding after dose suspension in another one. With regard to effectiveness, the response in the 3 patients was varied. The drug was considered to be safe, as there were only mild adverse reactions. Although further studies and long-term follow-up are required, these results show that romiplostim could be considered an alternative to immunosuppressive therapies, such as rituximab, or splenectomy in refractory chronic ITP.     

Increasing observation rates in low‐risk pediatric immune thrombocytopenia using a standardized clinical assessment and management plan (SCAMP®)

An observational approach is recommended in newly diagnosed children with immune thrombocytopenia (ITP) at low risk of bleeding; however, there is no standard definition of risk. A standardized clinical assessment and management plan (SCAMP^®), a modifiable practice guideline, was implemented and revised (SCAMP‐1 and SCAMP‐2) and applied to 71 newly diagnosed patients with ITP. The Buchanan and Adix bleeding score guided treatment and was modified by stratifying by low‐ and high‐risk grade 3 bleeding in SCAMP‐2. Observation rates increased from 40% to 74% from SCAMP‐1 to SCAMP‐2 (P < 0.05) with no bleeding complications. We propose a modified bleeding score that increased observation rates in low‐risk patients with ITP.     

Evaluation of a simple immunodiffusion technique for quantitation of platelet-associated immunoglobulin G in childhood immune thrombocytopenias

Platelet-associated IgG (PAIgG) was quantitated in 33 children with immune thrombocytopenia and platelet counts less than 100 X 10(9)/liter using a simple radial immunodiffusion (RID) assay. Elevated PAIgG levels were found in 76% (16/21) of children with acute idiopathic thrombocytopenic purpura (ITP), 88% (7/8) of children with chronic ITP, and all four children studied with systemic lupus erythematosus and thrombocytopenia. Normal PAIgG values were found in children with the following disorders: malignancy and chemotherapy-related thrombocytopenia; ITP in remission (platelet counts greater than 150 X 10(9)/liter); various nonimmune hematologic disorders and juvenile rheumatoid arthritis, these children having normal platelet counts. In children with acute ITP, elevated PAIgG values at initial presentation fell to within the normal range when clinical remission occurred. The RID assay can be easily established in most hematology laboratories and has the advantage that solubilized "test" platelets used in the assay can be stored frozen prior to analysis. We conclude that this simple technique is of value in the evaluation of childhood thrombocytopenic states and yields results comparable to those reported using more complex antiplatelet antibody assays.     

Clinical practice: immune thrombocytopenia in paediatrics

Immune thrombocytopenia (ITP) is a disease affecting both children and adults. It is defined as acquired isolated thrombocytopenia caused by the autoimmune production of anti-platelet antibodies. Childhood ITP most frequently occurs in young children who have been previously well, although a viral respiratory tract infection often precedes thrombocytopenia. A benign and self-limiting course is common, but major bleeding complications such as intracranial haemorrhage may occur. Yet one cannot predict which child will have a prolonged course of thrombocytopenia and who will develop an intracranial haemorrhage. In children without atypical characteristics, only minimal diagnostic investigations are needed, and most paediatric ITP patients do not need platelet-enhancing therapy even though various treatment options are available. A “watch and wait” strategy should be considered in paediatric patients with mild disease. Steroids, intravenous immunoglobulin G or anti-D immunoglobulin are the current first-line therapeutic measures for children at risk for severe bleeding. When life-threatening bleeding occurs, a combination of therapies is needed. In this review, we summarise the current knowledge on primary ITP in children and adolescents.     

妊娠合并血小板减少与新生儿转归的分析

目的：探讨不同病因所致妊娠血小板减少与新生儿转归的关系。方法：选择2009年1月至2010年12月140例妊娠合并血小板减少的孕妇及其新生儿,孕妇根据血小板减少的病因分为4组：妊娠期血小板减少症（GT）组（n=94）;妊娠合并免疫性血小板减少性紫癜(ITP)组（n=30）;妊娠合并其他血液系统疾病（再障、骨髓增生异常综合征）组（n=12）;其他原因组（n=4）：妊娠期高血压综合征(PIH)、妊娠合并系统性红斑狼疮（SLE)、妊娠合并酒精性肝硬化等。比较4组新生儿的转归。结果：GT组早产率11.3%,ITP组早产率16.7%,两组比较差异无统计学意义（P>0.05）。妊娠合并其他血液系统疾病组早产率53.8%,明显高于GT组（P<0.01）和ITP组（P<0.05）。GT组和ITP组中分别有 2例（2%）和4例（13%）患新生儿先天性被动免疫性血小板减少症,其发生比率差异有统计学意义(P<0.05)。ITP组中1例（3%）患ITP,1例（3%）患Evans综合征。妊娠合并其他血液系统疾病组1例（8%）患颅内出血。其他原因组中1例（25%）患新生儿狼疮综合征。结论：不同病因所致妊娠期血小板减少可致不同的围产期母婴结局。     

Duration and morbidity of chronic immune thrombocytopenic purpura in children: five-year follow-up of a Nordic cohort

Aim: To describe the clinical course, morbidity and platelet recovery in an unselected Nordic cohort of children with chronic Immune Thrombocytopenic Purpura (ITP). Methods: Prospective 5‐year follow‐up of 96 children with ITP lasting more than 6 months, with reporting of hospital admissions, severity of bleeding episodes and stabilization of platelet counts above 20, 50 and 150 × 10⁹/L. Results: The estimated 5‐year recovery rate was 52%; exclusion of 12 splenectomized children did not change the estimate. Events eliciting admission to hospital occurred in 39 (41%). Major haemorrhages occurred in eight children (8%), including a nonfatal intracranial haemorrhage in one child (1%). The overall admission rate was 0.4/year of thrombocytopenia, decreasing during follow‐up as thrombocytopenia converted to milder degrees. Early recovery within 2 years of diagnosis occurred in 35%, was associated with low morbidity and was more likely in young children with abrupt onset of symptoms. Conclusion: In a Nordic cohort of children with chronic ITP, one half had recovered 5 years after diagnosis, more than half never required hospitalization and <10% experienced serious bleeding episodes, always with a platelet count <20 × 10⁹/L. Aggressive management can be restricted to the minority of children with continuing severe thrombocytopenia and frequent, clinically significant bleeding events.