Thrombocytopenic syndromes masquerading as childhood immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is the most common cause of thrombocytopenia in children and adolescents. However, there are a number of other diagnoses that are often mistaken for ITP. A 10-year retrospective chart review was performed at the Children's Hospital of Alabama to characterize ITP. Initially, 492 patients who had the coded diagnosis of ITP (ICD 287.3) were identified. However, 83 (17%) of patients were found to have alternative diagnoses on chart review. Of the 83 patients, 13 patients (3%) represented coding errors or study classification errors. The 70 remaining patients (14%) had an alternative explanation for their thrombocytopenia, consisting of 31 different diagnoses. The most common diagnoses were familial thrombocytopenia (10%), systemic lupus erythematosus (9%), hypersplenism (9%), neonatal alloimmune thrombocytopenia (7%), Wiskott-Aldrich syndrome (7%), or systemic infection (6%). In total, 16 of the patients (23%) were ultimately diagnosed with one of a number of congenital syndromes with concurrent thrombocytopenia. Although this review confirms that most children with thrombocytopenia are diagnosed with ITP, 14% of the study population manifested other diagnoses. The clinician evaluating a child with thrombocytopenia must keep an open mind about the possible diagnosis and perform a comprehensive and thoughtful evaluation based on the clinical picture. ITP must be a diagnosis of exclusion as misdiagnosis in a child with thrombocytopenia may have a significant impact on morbidity and mortality.     

Effects of COVID-19 vaccination on platelet counts and bleeding in children,adolescents, and young adults with immune thrombocytopenia

Coronavirus disease 2019 (COVID-19) vaccines rarely cause de novo immune thrombocytopenia (ITP) but may worsen preexisting ITP in adults. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines impact platelet counts and bleeding in children, adolescents, and young adults (C-AYA) with preexisting ITP is unknown. We report here the very limited effect of COVID-19 vaccination on platelet counts and bleeding in a single-center series of 2 C-AYA with ITP. No patient experienced worsening bleeding and only one child had a significant decrease in platelet count which improved spontaneously to her baseline without intervention. SARS-CoV2 vaccination was safe in C-AYA with ITP in this small cohort.     

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.     

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。     

Immune thrombocytopenia following successful treatment of cancer in children

A predisposition to developing immune thrombocytopenia (ITP) has not been reported in survivors of childhood cancer. We report a case series of childhood cancer survivors who developed an isolated thrombocytopenia in the presence of a normocellular bone marrow. Five children, two with endodermal sinus tumors and three with acute lymphoblastic leukemia, developed ITP at a median of 4 years (range: 0.2-8 years) after completion of therapy. We suggest the association of ITP in survivors of childhood malignancy may not be co-incidental as chemotherapy may cause persistent immune dysfunction.     

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.     

Is it safe to avoid bone marrow examination in suspected itp?

Two children with suspected ITP are described. One child was treated outside with corticosteroids and was diagnosed acute lymphoblastic leukemia. Another child was fresh and diagnosed as acute myeloid leukemia on bone marrow aspirate examination. Both the children had no physical or peripheral smear finding suggestive of leukemia. We suggest that a bone marrow examination is required in developing countries for evaluation of thrombocytopenia before labeling it an immune thrombocytopenic purpura.     

Management of human immunodeficiency virus-associated thrombocytopenia with intravenous gamma globulin

A 17-month-old boy in whom immune-mediated thrombocytopenia (ITP) was the presenting manifestation of infection with human immunodeficiency virus (HIV) is being successfully managed with intermittent high-dose intravenous gamma globulin (IVIG) allowing maintenance of hemostatic platelet counts while avoiding the immunosuppression associated with other therapeutic modalities used to treat ITP. He continues to demonstrate marked responsiveness to IVIG, and has been maintained on weekly or bimonthly infusions for 12 months. The serendipitous documentation of HIV infection prior to IVIG therapy for immune-mediated thrombocytopenia in this child documents the importance of HIV testing prior to IVIG therapy to prevent erroneous assignment of IVIG as the vehicle responsible for transmission of HIV infection. This case history also documents the importance of HIV testing in the diagnostic evaluation of immune-mediated thrombocytopenias.     

在慢性免疫性血小板减少症患儿中甄别原发性免疫缺陷症

原发性免疫缺陷症(primary immunodeficiency,PID)是一组由免疫通路上特定功能性位点突变引起免疫调控异常的遗传性疾病,免疫性血小板减少为其常见表现,且病程迁延、反复,呈现慢性免疫性血小板减少状态.而免疫性血小板减少症(immune thrombocytopenic purpura,1TP)是儿童...     

Attenuated form of Evans syndrome among pediatric ITP patients

Long term follow up of adult patients with immune thrombocytopenic purpura (ITP) have shown evolvement of secondary autoimmune diseases such as SLE, Evans syndrome, autoimmune neutropenia, Graves disease etc. We studied 30 cases of pediatric ITP patients for evidence of hemolysis to assess the possibility of Evans like syndrome. Measurement of free serum haptoglobin, a sensitive indicator of red cell destruction was used after careful exclusion of micro angiopathic hemolysis, SLE or overt Evans Syndrome. Results showed abnormally low level of free serum haptoglobin in 11 of the 30 (36.7%) patients compared to that in 20 age matched controls (P < 0.001) as an evidence of hemolysis. Our data in pediatric patients is similar to that reported in adult ITP cases and support the observation of Evans made 50 years ago that there is a spectrum like relationship between primary thrombocytopenia and hemolytic anemia. Thus the concept of attenuated form of Evans syndrome could be considered, in group of patients with ITP in pediatric age group.     

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。     

Antiplatelet antibodies in chronic adult immune thrombocytopenic purpura: assays and epitopes

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by thrombocytopenia due to autoantibody-induced platelet destruction. The majority of these autoantibodies are directed to epitopes on either glycoprotein (GP) IIb-IIIa or GPIb-IX. The newer antigen-specific autoantibody assays are capable of detecting both platelet-associated and plasma autoantibodies and have a definite role in the diagnosis of immune thrombocytopenia. A positive assay provides strong evidence for the presence of immune thrombocytopenia both in chronic ITP and in other diseases where immune thrombocytopenia may occur, such as collagen vascular disease and lymphoproliferative disorders. However, a negative assay does not rule out the presence of ITP. Somewhat concerning is the large number of patients who have negative assays. Several possible explanations for these observations are discussed. Recent studies have localized some ITP autoepitopes to specific regions of GPIIb-IIIa and GPIb-IX. Most autoepitopes on GPIIb-IIIa are conformational, in view of their dependence on divalent cations, and are localized to the N-terminal portion of GPIIb, while the GPIb-IX autoepitopes that have been identified are localized to GPIb amino acids 333-341.     

Two new cases of thrombocytopenia absent radius (TAR) syndrome: clinical, genetic and nosologic features

Two unrelated children affected by TAR syndrome, autosomic recessive disease with congenital thrombocytopenia and bilateral radial aplasia, are described. In the first case a mild thrombocytopenia has been compatible with a fairly normal life until the second year of age. The other child shows radial aplasia associated with other anomalies of the upper limbs, severe thrombocytopenia and leukemoid reaction. The relationship among TAR syndrome, Fanconi's anemia and Roberts' syndrome are briefly discussed.     

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.     

Bernard-Soulier syndrome revealed by major neonatal thrombocytopenia]

Bernard-Soulier syndrome (BSS) is a congenital autosomal recessive bleeding disorder characterised by giant platelets, the lack of thrombocytopenia or a moderate one, prolongation of skin bleeding time, and absent platelet aggregation in response to ristocetin. We report a case of BSS revealed by major neonatal thrombocytopenia. A newborn was admitted for thrombocytopenic purpura initially believed to be due to a maternal auto-immune thrombocytopenia. Because of the persistence of the thrombopenia till the age of 7 months despite therapy by corticosteroids and immunoglobulins, and because of the detection of anti-1b antiplatelets antibodies after transfusion, BSS diagnosis was evoked. In such a situation of major thrombocytopenia, the main therapeutic measure is prevention. Therapy by DDAVP may be used after the age of 3 years in situations of high haemorrhagic risk. This case report underlines the importance of a precise diagnosis in front of a maternal thrombocytopenia and the possibility of antenatal diagnosis of BSS.     

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.     

Persistent thrombocytopenia following dengue shock syndrome

Though thrombocytopenia is one of the hallmarks of dengue hemorrhagic fever/ dengue shock syndrome, persistence of the same is rare. We report an 11 year-old child with dengue shock syndrome, who developed persistent thrombocytopenia. The possible mechanisms are discussed.     

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura

Platelet-associated IgG was studied in children with acute and chronic ITP and in patients with thrombocytopenic SLE, using the microtiter solid-phase radioimmunoassay. Of the children with acute ITP, 85% had elevated PAIgG levels. The degree of elevation of PAIgG at onset of disease did not correlate with the development of chronicity. Of the children with acute ITP, clinically and hematologically indistinguishable from the rest, 15% had normal PAIgG values. All of 22 children with chronic ITP had elevated PAIgG values. Although there was good correlation between the platelet count and the PAIgG value in children with chronic ITP, the association was not as striking in those with acute ITP; thus, factors in addition to the level of PAIgG may contribute to the thrombocytopenia in the latter group. Patients with SLE and thrombocytopenia had higher values of PAIgG than would be predicted from the platelet count; the PAIgG value is probably not the only factor determining the degree of immune thrombocytopenia.