原发性免疫性血小板减少症儿童生活质量及其影响因素研究进展

原发性免疫性血小板减少症(primary immune thrombocytopenia,ITP)是儿童最常见的出血性疾病,常表现为皮肤和黏膜出血,罕见颅内出血。儿童ITP为急性自限性疾病,大多数出血倾向重但预后良好;少数迁延反复,呈慢性趋势。尽管儿童ITP严重出血风险低,但慢性ITP血小板计数反复减少常引起家属的担忧,故患儿的日常活动常会受到限制。此外,治疗药物引起的相关不良反应、对病程迁延及疾病预后的担忧等都会影响到患儿的健康及相关生活质量。该文主要针对ITP儿童的生活质量及主要影响因素研究进展展开论述。     

Role of parvovirus B19 infection in childhood idiopathic thrombocytopenic purpura

Although parvovirus B19 exhibits a strong tissue-tropism for erythroid progenitor cells leading to anaemia, several case reports indicate that parvovirus B19 infection may also cause the development of thrombocytopenia. Despite recent studies, the frequency and clinical relevance of this association have remained questionable. Consequently, and in view of the paucity of evidence regarding a viral aetiology for idiopathic thrombocytopenic purpura (ITP), we examined the role of parvovirus B19 in 47 children with newly diagnosed ITP. Specific viral DNA indicating a current or recent parvovirus B19 infection was demonstrated in 6 of 47 patients (13%) employing the polymerase chain reaction technique. Our study suggests that children with ITP and associated parvovirus B19 infection are characterized by acute onset of profound thrombocytopenia. Among the parvovirus B19 positive children, duration of disease was brief in three children treated with immunoglobulin but chronic in the remaining three patients given high-dose steroids. Prospective studies are needed to confirm these initial observations. This virus should be considered as a possible aetiologic agent in some children with ITP.     

Intended management of children with acute idiopathic thrombocytopenic purpura: a national survey

OBJECTIVE: In Australia acute idiopathic thrombocytopenic purpura (ITP) is mainly treated by paediatricians (either general paediatricians or paediatric haematologists/oncologists). A survey was conducted to gauge the current practice of treating children with acute ITP in Australia. METHODS: All practising Australian paediatricians registered by the Royal Australasian College of Physicians were surveyed regarding their intended management of children with acute ITP. The questionnaire, adapted from a study of paediatric haematologists/oncologists in North America, presented four clinical scenarios of children with acute ITP with a platelet count of 3000 x 10(9)/L, with and without mucosal bleeding (wet and dry purpura, respectively). Questionnaires were returned by mail or filled in online at a dedicated webpage. RESULTS: Five hundred and sixty-three of 1097 (51%) paediatricians responded to the survey. Data from 140 who had treated at least one child with ITP in the previous 12 months were analysed. Respondents indicated that children with acute ITP are usually or always hospitalised (58-92%) and that 48% would be given active treatment, even with dry purpura. Various regimens of i.v. immunoglobulin or corticosteroids are used when treatment is administered. In comparing Australian and North American management of acute ITP there were many similarities, although Australian paediatricians were less likely to arrange a bone marrow aspirate if corticosteroids were prescribed. CONCLUSIONS: There is great variation in the intended management of children with acute ITP in Australia. Previously published management recommendations regarding investigation and treatment have had little impact on intended practice. Prospective studies are required to evaluate hypotheses so as to produce evidence-based recommendations for treatment of patients with acute ITP.     

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.     

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...     

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.     

Idiopathic thrombocytopenic purpura: beyond consensus

Idiopathic thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder encountered by pediatricians. Most children with ITP have minimal bleeding and complete platelet count recovery within weeks to months. Therapy for ITP has ranged from close observation without medical intervention to aggressive management with corticosteroids, intravenous immunoglobulin G, or anti-D immune globulin. The topic of ITP has incited great debate among practitioners, and this debate prompted the development of ITP practice guidelines by the British Paediatric Haematology Group in 1992 and by the American Society of Hematology in 1996. A better understanding of the clinical course of, risk for significant bleeding in, and optimal evaluation and therapy of childhood ITP will require carefully designed, multicenter, clinical trials.     

Idiopathic thrombocytopenic purpura in childhood: Twenty years of experience in a single center

Background: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder with a variable clinical course. Methods: A retrospective analysis was carried out of ITP patients presenting to a pediatric hematology‐oncology department during a period of 20 years, with a focus on treatment and outcome. Results: One hundred and twenty‐four cases were recorded (mean patient age, 8.4 years). Forty‐nine children (39.5%) had platelet counts <10 000/µL at diagnosis. No episode of severe bleeding was observed. Peak incidence was observed during spring and summer. Respiratory infections proceeded in 58% of cases. Treatment consisted of i.v. immunoglobulin (IVIG) in 93 children at four dosing schedules. Sixteen children received corticosteroids, 10 children received anti‐D immunoglobulin and 14 received no treatment. Recovery was observed in 67% of children on IVIG and in 50% on anti‐D globulin. Eight patients did not respond initially and received corticosteroids. Three children with refractory thrombocytopenia received anti‐CD20 (rituximab). Fourteen children (11%) had persistent/chronic disease. In 10 of them recovery was observed in 13 months–8 years. Splenectomy was performed in six children with resistant/chronic disease. Conclusion: ITP has a benign course in the majority of cases. Anti‐D globulin can effectively be used as an alternative first‐line treatment. Rituximab can successfully be used in refractory cases, while splenectomy has currently limited indications.     

Idiopathic thrombocytopenic purpura of childhood

Idiopathic thrombocytopenic purpura (ITP) is a benign hemorrhagic disorder characterised by peripheral thrombocytopenia and increased megakaryocytes in the bone marrow. The exact pathogenesis of ITP is not well understood. The adherence of viral induced immune complexes to the platelet membrane is thought to trigger the phagocytosis of damaged platelets by macrophages in the reticuloendothelial system. The role of platelet associated IgG in the pathogenesis of ITP is under investigation. Although spontaneous recovery is observed in 80–90% of patients, a short course of steroid therapy is recommended to reduce the duration of thrombocytopenia. The steroids however, have no influence on the course or outcome of the disease, and their possible role in reducing the incidence of intracranial hemorrhage (ICH) is unknown. Emergency management of patients presenting with signs and symptoms suggestive of ICH is essential to prevent the fatal outcome. Approximately 10–20% of patients develop chronic ITP. Splenectomy, considered the treatment of choice in these patients, is not always curative. The post-splenectomy sepsis also imposes a great risk for these individuals. Recent experience with intravenous immunoglobulin (IV IgG) treatment indicates that the splenectomy could safely be deferred, or even avoided in chronic ITP. The use of IV IgG in acute ITP is being investigated.     

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.     

Idiopathic thrombocytopenia,initial illness and long term follow up.

One hundred and eighty one children with thrombocytopenia for which no cause could be found have been studied. One patient died with severe bleeding possibly from disseminated intravascular coagulation and one developed cerebral haemorrhage, both within two weeks of onset. Ninety one per cent of the 135 with acute disease but only 36% of those with chronic disease remitted spontaneously. Twenty per cent of spontaneous remission occurred more than one year after onset. Six patients have run an intermittent course for 10 to 20 years. Four patients have had symptomless thrombocytopenia for between 10 and 30 years. Of 32 children treated by splenectomy 24 maintained normal platelet values thereafter. One boy died from pneumococcal septicaemia two years after splenectomy but he had not received prophylactic penicillin. One hundred and fifty eight patients were followed up 3 to 37 years (mean 16.4 years) after onset. None who recovered spontaneously or after splenectomy had had further bleeding problems. No patient nor immediate relative had developed other autoimmune disease. We consider that a short course of corticosteroids immediately after diagnosis is justified in all cases even though we cannot produce proof that it influences the course of the disease. We do not accept any place for long term immunosuppressant treatment.     

Steroid treatment of idiopathic thrombocytopenic purpura in children. Preliminary results of a randomized cooperative study

Preliminary data from a prospective randomized study of the use of a short course of adrenocorticosteroids in 73 children with ITP demonstrates a significant advantage of moderate dose (60 mg/m2/day p.o. X 21 days) prednisolone therapy in decreasing the duration of severe thrombocytopenia in most patients. The period of risk for serious bleeding, as reflected in the Rumpel-Leede test, was also significantly reduced. The number of children who developed chronic thrombocytopenia, although small in both groups, appeared to be uninfluenced by steroid therapy. No side effects or serious complications were noted in this trial.     

Hospitalization of children with acute immune thrombocytopenic purpura – is it necessary?

OBJECTIVE:

To identify a target group of children with acute immune thrombocytopenic purpura (ITP) that may not require hospitalization for management.

METHODS:

A retrospective chart review was conducted of all children admitted over a two-year period to a tertiary care paediatric hospital with the diagnosis of acute ITP. Patients were classified according to typical and atypical presentations. Typical patients were defined as those aged between one and 10 years, with no hepatomegaly or significant splenomegaly and who had typical laboratory features for ITP. Patients who did not meet these criteria were categorized as atypical. Outcome measures included length of stay (LOS) in hospital; frequency of bone marrow aspiration (BMA); type of treatment; incidence of intracranial hemorrhage (ICH) or severe bleeding; and admission and discharge platelet counts.

RESULTS:

There were 74 patients hospitalized for a mean of 3.6 days. No patients suffered an ICH or bleeding requiring transfusion. Patients with typical presentations (42) were compared with patients with atypical presentations (32) and were not significantly different for clinically important outcomes such as admission and discharge platelet counts, serious complications or type of therapy. Typical patients had significantly fewer BMAs than did atypical patients – 22 of 42 (52%) versus 25 of 32 (78%) (P=0.02), and a shorter LOS – 3.1 (±0.9) days versus 4.2 (±1.8) days (P=0.01).

CONCLUSIONS:

Children presenting with ITP have a low incidence of bleeding complications and many of these patients can be managed as outpatients. A multicentre study is needed to properly delineate a low risk group suited for outpatient medical management.     

Peritoneal hemorrhage due to a ruptured ovarian cyst in ITP

Immune thrombocytopenic purpura in children rarely causes severe bleeding. The incidence of intracranial hemorrhage is approximately 0.2% to 1.0%, and severe bleeding (defined as persistent epistaxis, melena, menorrhagia, gastrointestinal bleeding, etc, requiring hospitalization or transfusion) occurs in only 5% of patients. Epstein-Barr virus (EBV) associated idiopathic thrombocytopenic purpura (ITP) tends to behave similarly to non-EBV - associated ITP with no increase in hemorrhagic complications and only a small increase in time to remission. Immune thrombocytopenic purpura diagnosed in adolescence is more likely to be chronic then in childhood ITP, but has a higher rate of spontaneous resolution than in adults. However, females in this age group are in their early childbearing years and present a unique set of possible hemorrhagic complications not seen in younger patients. We present the case of an 18-year-old female with EBV-associated ITP, who developed a severe intra-abdominal bleed secondary to a hemorrhagic ovarian cyst.     

Clinical standards in the reformed NHS.

A UK survey was carried out to discover the frequency, circumstances, and outcome of intracranial haemorrhage (ICH) complicating idiopathic thrombocytopenic purpura (ITP) of childhood. A questionnaire was circulated through the membership of the UK Paediatric Haematology Forum, and thence to local paediatricians and haematologists. It sought information on any child with ITP who had had an ICH during the 20 year period to January 1994. Fourteen instances were discovered, seven before 1984 and seven after. Six children survived the event with minimal or no sequelae, four without craniotomy. An immediately precipitating cause was noted in four; two had arteriovenous malformations and two suffered head injuries. The event occurred over two weeks from diagnosis in seven cases and over two months in five. All children were profoundly thrombocytopenic at the time of their intracranial bleed. By calculation the 14 children would have represented some 0.1% of the total with ITP during the period under review. ICH in childhood ITP may have a precipitating cause and is not necessarily fatal. There is no period of maximum risk, and it can occur at any time during the course of the illness when the platelet count is less than 10-15 x 10(9)/l. It is an extremely rare event and previous estimates of its incidence may have been too high.     

Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Paediatric Haematology Forum of the British Society for Haematology

A UK survey was carried out to discover the frequency, circumstances, and outcome of intracranial haemorrhage (ICH) complicating idiopathic thrombocytopenic purpura (ITP) of childhood. A questionnaire was circulated through the membership of the UK Paediatric Haematology Forum, and thence to local paediatricians and haematologists. It sought information on any child with ITP who had had an ICH during the 20 year period to January 1994. Fourteen instances were discovered, seven before 1984 and seven after. Six children survived the event with minimal or no sequelae, four without craniotomy. An immediately precipitating cause was noted in four; two had arteriovenous malformations and two suffered head injuries. The event occurred over two weeks from diagnosis in seven cases and over two months in five. All children were profoundly thrombocytopenic at the time of their intracranial bleed. By calculation the 14 children would have represented some 0.1% of the total with ITP during the period under review. ICH in childhood ITP may have a precipitating cause and is not necessarily fatal. There is no period of maximum risk, and it can occur at any time during the course of the illness when the platelet count is less than 10-15 x 10(9)/l. It is an extremely rare event and previous estimates of its incidence may have been too high.     

Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Paediatric Haematology Forum of the British Society for Haematology.

A UK survey was carried out to discover the frequency, circumstances, and outcome of intracranial haemorrhage (ICH) complicating idiopathic thrombocytopenic purpura (ITP) of childhood. A questionnaire was circulated through the membership of the UK Paediatric Haematology Forum, and thence to local paediatricians and haematologists. It sought information on any child with ITP who had had an ICH during the 20 year period to January 1994. Fourteen instances were discovered, seven before 1984 and seven after. Six children survived the event with minimal or no sequelae, four without craniotomy. An immediately precipitating cause was noted in four; two had arteriovenous malformations and two suffered head injuries. The event occurred over two weeks from diagnosis in seven cases and over two months in five. All children were profoundly thrombocytopenic at the time of their intracranial bleed. By calculation the 14 children would have represented some 0.1% of the total with ITP during the period under review. ICH in childhood ITP may have a precipitating cause and is not necessarily fatal. There is no period of maximum risk, and it can occur at any time during the course of the illness when the platelet count is less than 10-15 x 10(9)/l. It is an extremely rare event and previous estimates of its incidence may have been too high.     

Neutropenia following IVIG therapy in pediatric patients with immune-mediated thrombocytopenia

It has been observed that some children with immune-mediated thrombocytopenia (ITP) who are treated with intravenous immunoglobulin (IVIG) experience a decline in their absolute neutrophil count (ANC). The aim of this study was to investigate the incidence of neutropenia following IVIG therapy in a large cohort of children with ITP. This retrospective comparative cohort study determined the incidence of neutropenia in 104 patients (110 treatment courses) admitted for ITP to the Children's Hospital of Philadelphia from January 2000 to October 2003. Post-treatment ANCs were compared between patients who received IVIG and patients who received anti-D immunoglobulin. The incidence of neutropenia in each group was analyzed using the Fisher exact test. Pretreatment ANCs were not significantly different between the two treatment groups (P = 0.72). Neutropenia (ANC < 1,500/microL), developed during 18 of 64 (28%) treatment courses with IVIG, compared with 0 of 46 (0%) treatment courses with anti-D immunoglobulin (P < 0.001). This study suggests that IVIG may cause neutropenia commonly in children with ITP. While this is likely to be a transient condition, its recognition may affect clinical decisions such as the need for a bone marrow examination.     

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS)

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.     

Management of immune thrombocytopenic purpura

Childhood immune thrombocytopenic purpura (ITP) is an uncommon, generally self-limiting, heterogeneous condition usually with a good outlook. Most children recover quickly without serious bleeding complications irrespective of specific treatment to raise the platelet count. The low platelet count was thought to equate to a risk of serious bleeding, but several population studies have confirmed that this risk is low, around 3–4%, and intracranial haemorrhage is rare. Most children do not require active treatment. Assessment of bleeding by a clinical score is required together with assessment of quality of life issues that help to determine whether invasive investigations and treatment are worse for the child than the illness itself. Advances have been made in understanding the pathogenesis, and new treatments have been developed, some of which have been tried with success in children.