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.     

High-Dose Intravenous Immunoglobulin as Single Therapy in a Child with Autoimmune Hemolytic Anemia

Between 1975 and 1992 450 children with idiopathic thrombocytopenic purpura (ITP) were diagnosed, and of those 100 (22%) developed the chronic form of the disease. Approximately half the patients with chronic ITP presented with mild to moderate hemorrhagic manifestations at the onset of purpura (30 cases) andlor later during the course of the disease (25 cases). The incidence of intracranial hemorrhage was 1 %, and the mortality rate due to overwhelming septicemia after splenectomy was also 1%. Overall one-third of the patients received no therapy; two-thirds of them went into spontaneous remission within 8 months to 8 years from the onset of ITP. Steroids given in conventional or high doses (51 cases) achieved a transient (if any) rise in platelet count, but in no case were steroids curative. Remission related to intravenous immune globulin (IVIG) therapy was noticed in 38.5% of the children (10 of 26) after variable courses. The response rate to splenectomy was 95.0%. Ultimately the long-term outcome in children with chronic ITP was as follows: remission, 58 cases (spontaneous, 30; after IVIG therapy, 10; after splenectomy, 18); hemostatic platelet values, 22 cases (spontaneous, 16; after IVIG, 5; after splenectomy, I). Thirteen children were lost in follow-up, and 7 remain thrombocytopenic but asymptomatic. These data indicate that chronic ITP in childhood runs a benign course in most cases and may remit with or without therapy euen several years from onset. Therefore, therapeutic intervention has to be individvalized, and splenectomy, which is not always safe, should be reserved for problematic cases that fail to respond to conventional therapeutic modalities.     

Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Mean age at diagnosis and duration of follow-up were similar for both groups. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a 125I-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.     

Immunological events in acute measles influencing outcome.

77% of 30 children with measles who had severe lymphopenia (less than 2000/mm3; less than 2.0 x 10(9)/1) within 2 days of appearance of rash (group A) subsequently died or progressed to chronic chest disease. This was significantly worse than the outcome in 30 children with measles who had lymphocyte counts more than 2000/mm3 (more than 2.0 x 10(9)/1) (group B) of whom 67% recovered. In group A children the persistence of severe lymphopenia (caused by a reduction in T- and B-cells) for at least 15 days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in group A was slower and incomplete 42 days from appearance of the rash in those who subsequently died or developed chronic chest disease compared with those who recovered. All patients who died failed to produce adequate measles antibodies. The therapeutic implications and immunopathological significance of these findings for chronic complications after acute measles are discussed.     

特发性血小板减少性紫癜患儿血清微小病毒B_(19)检测及意义

目的探讨人微小病毒B19(HPVB19)感染与儿童特发性血小板减少性紫癜(ITP)发病的关系。方法采用酶联免疫法(ELISA)对46例ITP患儿利30例健康儿童的血清标本进行HPVB19-IgM、IgG及血小板相关抗体检测。结果46例ITP患儿血清中HPVB19抗体总刚性率43.48%(20/46),30例健康儿童HPVB19-IgM、IgG均为阴性,2组间差异有统计学意义(P<0.01);ITP组中急性型与慢性型之间HPVB19抗体总阳性率差异有统计学意义(P<0.05);病毒感染刚性患儿的血小板相关抗体明显高于病毒感染阴性患儿,差异有统计学意义(P<0.01)。结论ITP患儿血清中HPVB19抗体总刚性率高,尤其是急性型;HPVB19感染后可导致血小板相关抗体升高而致血小板减少。     

Immunological events in acute measles influencing outcome

77% of 30 children with measles who had severe lymphopenia (less than 2000/mm3; less than 2.0 x 10(9)/1) within 2 days of appearance of rash (group A) subsequently died or progressed to chronic chest disease. This was significantly worse than the outcome in 30 children with measles who had lymphocyte counts more than 2000/mm3 (more than 2.0 x 10(9)/1) (group B) of whom 67% recovered. In group A children the persistence of severe lymphopenia (caused by a reduction in T- and B-cells) for at least 15 days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in group A was slower and incomplete 42 days from appearance of the rash in those who subsequently died or developed chronic chest disease compared with those who recovered. All patients who died failed to produce adequate measles antibodies. The therapeutic implications and immunopathological significance of these findings for chronic complications after acute measles are discussed.     

Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease

AIM: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. METHODS: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at least one platelet count <30 x 10(9)/l. RESULTS: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10 x 10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97). CONCLUSION: In the Nordic countries, ITP mainly affects children aged 0-7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.     

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura

Childhood ITP is an acquired hemorrhagic disorder with a heterogeneous clinical course. We measured PAIgG levels in 20 children with ITP (7 acute, 13 chronic). Both groups had significantly greater PAIgG values than age-matched normal subjects and thrombocytopenic controls (P less than 0.001). In addition, PAIgG values in chronic ITP were significantly lower than those in acute ITP (P less than 0.003). Serial PAIgG values were obtained in some patients; most returned to normal in association with clinical recovery. The measurement of PAIgG is useful in the diagnosis and follow-up of childhood ITP. PAIgG values may assist in differentiating acute and chronic disease in children.     

Immunological study of childhood acute ITP at onset.

We attempted to search for any specific change in the immune system during the onset of childhood acute immune thrombocytopenic purpura (ITP) in order to clarify the pathophysiology of acute ITP by examining the lymphocyte subset, lymphocyte blastogenic response, serum complements, and immunoglobulins in 18 patients with childhood acute ITP and 18 controls (control values after normalization). At the onset of acute ITP, the levels of serum complements and IgG and IgA were found to be within the normal ranges, but serum IgM levels were greater than 200 mg/dL in six cases among 18 patients. Lymphocyte blastogenic response to phytohemagglutinin (PHA) and concanavalin A (ConA) was depressed in patients relative to controls (PHA: p less than 0.05, ConA: p less than 0.01). Lymphocyte blastogenic response to pokewood mitogen (PWM) was lower than that of the control, but no statistical significance was observed. There was no difference in the proportion of CD3, CD4, CD8, SmIg, SmIgG, SmIgM, SmIgA, and SmIgD. The CD4/CD8 ratio was not different from that of controls. The proportion of CD38 was higher than that of control, but no significant difference from the control was observed. Increase in the serum IgM level and proportion of CD38 and depressed lymphocyte blastogenic response may be the influence of preceding infection. It has been reported that the CD4/CD8 ratio is depressed due to an increase in the CD8 level in acute and convalescent phases of viral infection. However, the proportion of CD8 was not necessarily increased in our patient in whom preceding infection was obvious. The immunological status of the patients with acute ITP at onset differs from that after infection.     

幽门螺杆菌在儿童特发性血小板减少性紫癜的感染状况分析

目的探讨特发性血小板减少性紫癜(ITP)患儿幽门螺杆菌(Hp)感染状况及相关危险因素。方法用粪便检测Hp抗原及血清检测Hp抗体两者联合检测62例慢性ITP患者,88例急性ITP患者及150例健康儿童,两者均为阳性判断为Hp感染。对每个研究对象进行问卷调查。结果急、慢性ITP患儿、健康儿童三者感染率比较无统计学意义(P<0.05)。HP感染家族史、口嚼食物喂养史、啃手指/笔/玩具、低人均居住面积为ITP患儿Hp感染的易感因素;年龄小、有专用餐具为ITP患儿Hp感染的保护因素。结论本研究不表明Hp感染与ITP发病相关。     

Platelet-Associated IgG in Children - Values and Evaluation of PAIgG in Various Thrombocytopenias -

Platelet-associated IgG (PAIgG) levels were measured in 60 children with ITP (46-chronic, 14-acute) using Fab-anti Fab radioimmunoassay method described by McMillan et al. In some patients platelet binding IgG in serum (PBIgG) was also determined at the same time. Patients with ITP had significantly greater PAIgG levels than 30 normal subjects and 13 non-immune thrombocytopenic controls. Elevated PAIgG values did not correlate with parameters of platelet size (mean platelet volume; MPV and percentage of large platelet; PLP) and so these data indicated that high levels of PAIgG in ITP were not due to nonspecific adhesion of serum IgG to megathrombocytes usually increased in this disorder, but due to specific immunological reaction. PBIgG IgG values were also elevated in patients with pretreated chronic ITP, but high levels remained even after successful splenectomy. Furthermore, serial determination of PAIgG values were obtained in some patients with chronic ITP who underwent splenectomy and with acute ITP who achieved spontaneous remission. PAIgG returned to normal levels when thrombocytopenia disappeared. PAIgG seems to be the most reproducible indicator which reflects transition of the clinical picture in this disorder.     

Intravenous immunoglobulin for idiopathic thrombocytopenic purpura (ITP) in childhood

IgG-SRK (identical with Sandoglobulin) is a polyvalent IgG concentrate obtained by modified alcohol cryoprecipitation, including mild acidification at pH 4. This product was given in high doses intravenously for the treatment of six children with acute ITP, four children with intermittent ITP, and three children with severe chronic idiopathic thrombocytopenic purpura (ITP). An impressive initial response was observed in all patients, the extent of which may be of prognostic significance in acute ITP. Maintenance therapy was required in two of six patients with acute ITP, in three out of four patients with intermittent ITP, and in all of the patients with severe chronic ITP. In the cases of severe chronic ITP, the disease could not be adequately controlled over long periods of time, but bleeding episodes subsided or became considerably less frequent. Although little is known of the effects of IgG-SRK, possible mechanisms were discussed. It is emphasized that a new model has been discovered to study the interrelations between structure and function of human immunoglobulin molecules.     

Idiopathic thrombocytopenic purpura in children. The case for management without corticosteroids

Acute ITP in children under 13 years of age is generally a benign, self-limited condition with spontaneous recovery occurring within a matter of days or weeks. Our analysis of platelet data indicate no advantage in terms of rate of recovery when steroids are used. In fact, the median of 3 weeks and mean of 3 1/2 weeks from onset to recovery in the nonsteroid-treated children were significantly better than the corresponding figures in the steroid-treated group. In addition, while reducing the risk of intracranial hemorrhage is generally given as the chief therapeutic rationale for using steroids, we have not seen a single case of ICH among 465 consecutive cases of acute ITP in children, the majority (93%) of whom did not receive steroids. On the other hand, adolescents, as adults, with ITP often have the autoimmune (chronic) form of the disease. In this group, corticosteroids may be of at least transient benefit and should be used.     

Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP.     

Chronic immune thrombocytopenic purpura in children: a survey of the canadian experience

BACKGROUND: Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. RESULTS: Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. CONCLUSIONS: The results from this study are consistent with published reports.     

Prevalence and Clinical Significance of Antithyroid Antibodies in Children with Immune Thrombocytopenic Purpura

Background and objective: To determine the prevalence and the clinical significance of thyroid autoantibodies and their influence on treatment response in children with idiopathic thrombocytopenic purpura (ITP). Patient and Method: We retrospectively analyzed the antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies from the records of 151 ITP patients who were admitted to the Pediatric Hematology Department of Gaziantep University between 2009 and 2012. Results: Anti-TPO and/or anti-TG was found positive in 38 (36.8%) of 103 patients whose thyroid autoantibody levels were measured. The comparison of positivity ratios of autoantibodies between acute and chronic ITP patients showed no significant difference. However, the separate comparison of each group of ITP patients with control group showed significantly high positivity ratios of autoantibodies in ITP patients. The initial mean platelet count of anti-TPO positive patients at diagnosis was significantly less than that of the negative patients (P = .008). One month after treatment, platelet count of anti-TPO positive patients was significantly less than that of the negative patients (P = .01). Moreover, the mean platelet counts of anti-TPO positive patients were significantly less than those of the negative patients after intravenous immunoglobulin treatment (P < .001). Conclusion: We demonstrated that the thyroid-autoimmune-diseases-related autoantibodies are frequently found in childhood ITP. Although no recommendation is found in international guidelines regarding screening for thyroid autoantibodies in patients with ITP, in view of the high incidence of antithyroid antibodies and their potential negative effect on treatment response, screening these patients for such antibodies would be recommended.     

儿童特发性血小板减少性紫癜患儿Th2相关细胞因子IL-4、IL-10与血小板相关抗体的检测及意义研究

探讨Th2相关细胞因子IL 4、IL 1 0与血小板相关抗体PAIgG、PAIgM在儿童ITP的发病机理中的作用。方法是采用双抗体夹心酶联免疫吸附试验 [ELISA]技术检测 30例ITP患儿血浆中IL 4、IL 1 0水平 ,同时检测PAIgG、PAIgM的水平 ,研究IL 4、IL 1 0对PAIgG、PAIgM的调节作用。结果显示 :( 1 )急性期ITP患儿IL 4、PAIgG、PAIgM水平均高于对照组 (P <0 .0 5)。( 2 )慢性ITP病例半年后IL 4、PAIgG、PAIgM仍然高于对照组 (P <0 .0 5) ,IL 4与血小板相关抗体水平呈显著正相关。 ( 3)病程中IL 1 0与对照组无明显变化。结论 :ITP患儿IL 4表达增加 ,提示Th2相关细胞因子比例失调 ,使血小板相关抗体增高为重要的致病因素之一。     

Directions for research in autoimmune thrombocytopenic purpura (ITP)

All attendees participated in a round-table discussion regarding directions for research in autoimmune thrombocytopenic purpura (ITP). Suggested areas for study were grouped into five main areas: (i) improved classification of ITP identifying subsets of patients with differing clinical syndromes and response to treatment, and those more likely to have serious bleeding manifestations; identification of patients with reduced thrombopoiesis was emphasized; (ii) studies aimed at elucidating the aetiology and pathophysiology of ITP, with emphasis on distinctions between acute and chronic ITP and between patients responsive or refractory to therapy; these studies focused on measures of humoral and cellular immune dysregulation; (iii) studies of platelet function in ITP, with the intent of defining these abnormalities and correlating them with the clinical manifestations of the disease; (iv) new approaches to treatment, particularly of refractory patients; and (v) a miscellaneous group, which included development of an ITP registry, evaluation of the "burden" of disease, investigation of mood changes in ITP, etc. The discussion was not intended to be all-inclusive, but focused on the content of other talks in this symposium. It is hoped that some of thesesuggestions will be further developed for investigation in multicentre co-operative studies to improve the diagnosis, understanding and treatment of ITP.     

Low-dose cyclosporin A therapy in children with refractory immune thrombocytopenic purpura

Although splenectomy is the most effective treatment for chronic idiopathic thrombocytopenic purpura (ITP), many post-splenectomy patients have recurrent thrombocytopenia refractory to multiple medical therapies. Three consecutive patients with relapsed ITP after splenectomy and who were refractory to multiple medical therapies were treated with low dose cyclosporin A (CsA). In all 3 patients, the platelet count increased dramatically within 1 month from the onset of CsA therapy. The only detectable toxicity was hypomagnesemia and mild hypertension in 1 patient. CsA may be efficacious in treating patients with chronic ITP, which is refractory to all medical and surgical therapies currently being used.     

Intracranial hemorrhage in childhood immune thrombocytopenic purpura

We retrospectively analyzed 750 patients with ITP for development of intracranial hemorrhage (ICH). Seventeen cases with age range of 10 months to 18 years were studied. Ten patients were of acute ITP and seven had chronic ITP. Nine patients developed ICH one month after the onset of ITP and five patients had ICH on presentation. ICH was precipitated by trauma in four patients and possibly the use of NSAIDs in one patient. Median platelets counts at the time of ICH were 12 × 10⁹/L (range 2–50 × 10⁹/L). Most patients were treated with corticosteroids. Four patients (24%) died due to ICH. Pediatr Blood Cancer 2009;52:529–531. © 2008 Wiley‐Liss, Inc.