Agenesis of the Corpus Callosum and Neural Crest Tumors

Hematologic abnormalities, including thrombocytopenia, are seen in HIV infection. Mi have previously reported elevated platelet-associated IgG (PAIgG) in thrombocytopenia in children associated with human immunodeficiency virus (HIV). In this study we prospectively monitored 40 HIV-infected infants and children to determine the significance of elevated PAIgG levels as they relate to thrombocytopenia. We also examined platelet eluatesfor the presence of HIV antibody and antigen. Of 16 patients with thrombocytopenia, 15 (93.7%) had elevated PAIgG. Of 24 patients with normal platelet counts, 21 (87.5%) had elevated PAIgG. On follow-up, none of the children with normal platelet counts and elevated PAIgG levels developed thrombocytopenia. Examination of the platelet eluates was negative for HIV antibody or P24 antigen. Although the sensitivity of an elevated PAIgG level in predicting thrombocytopenia is 93%, its specificity is only 13%. Elevated PAIgG levels are therefore not causally related to the development of thrombocytopenia in children.     

Prognostic implications for direct platelet-associated IgG in childhood idiopathic thrombocytopenic purpura

To determine the value of the direct platelet associated IgG (PAIgG) level as a prognostic indicator in childhood idiopathic thrombocytopenia purpura (ITP), 18 children with ITP were studied. Ten of the 18 had PAIgG levels measured at diagnosis, before any therapy. Of these 10 patients, six (Group I) had an acute course, with a mean initial platelet count of 15 X 10(9)/liter and a mean initial PAIgG level of 330.9 fg/plt. Four patients (Group II) had a chronic course, with a mean initial platelet count of 11 X 10(9)/liter and a mean initial PAIgG level of 38.3 fg/plt. There was no significant difference between the mean initial platelet count of Groups I and II (p greater than 0.10), but the initial PAIgG levels in those patients with an acute course were significantly higher than the levels in those patients with a chronic course (p less than 0.05). Of the original 18 patients, nine were splenectomized for chronic thrombocytopenia, with normalization of the platelet count in all instances. Of these splenectomized patients, five had platelet counts and PAIgG levels measured before and after splenectomy. All five had normal PAIgG levels following splenectomy. The PAIgG level is a good prognostic indicator for the clinical course of childhood ITP. A high PAIgG level suggests an acute course while a modestly elevated level suggests a chronic course. The PAIgG level normalizes in remission after splenectomy.     

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.     

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.     

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.     

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.     

Thrombocytopenia and human immunodeficiency virus in children

Thrombocytopenia occurs in 13% of children with symptomatic human immunodeficiency virus (HIV) infection. The clinical and laboratory course of 19 children infected with HIV with thrombocytopenia is described. Bone marrow aspirates showed normal to increased numbers of megakaryocytes. Levels of antiplatelet antibodies were increased in 80% of the children and circulating immune complexes were found in 74%. Clinically significant hemorrhage leading to anemia occurred in five patients, and CNS bleeding led to a fatal outcome in an additional three children. Spontaneous remission of thrombocytopenia occurred in three of the 19 subjects. High-dose IV gamma-globulin was effective in increasing the platelet counts of six of 15 patients (40%) but resulted in a sustained remission in only one subject. Oral prednisone was effective in increasing the platelet count of two thirds of those whose platelet counts could not be controlled by IV gamma-globulin. Bleeding manifestations were eliminated in all patients whose platelet counts increased significantly. Of the 11 children whose counts increased either spontaneously or as a result of therapy, eight remain alive (72%). In contrast, all of the eight patients whose platelet counts did not improve have died. Thrombocytopenia in children with HIV disease is engendered by immune mechanisms and is a major cause of morbidity and mortality. High-dose IV gamma-globulin and/or corticosteroids are temporarily effective in increasing the platelet count and reducing bleeding in about half of thrombocytopenic patients and are recommended for use. The ability to respond to therapy correlates with improved survival.     

Lymphocyte subset ratios and factor VIII usage in haemophilia.

Type and quantity of replacement treatment, together with haematological and immunological parameters were determined in 37 boys with severe haemophilia A and 41 children with other bleeding disorders. The quantity of factor VIII concentrate given to boys with severe haemophilia A (mean U/year) showed a significant inverse correlation with total white cell counts, lymphocyte counts, platelet counts, and the ratio of monoclonal antibody defined T lymphocyte subsets, T4 and T8 (T4:T8). Of the boys with severe haemophilia A, 49% had inversed T4:T8 ratios and 24% had thrombocytopenia. Treatment with high dose factor VIII concentrate (more than 25 000 U/year) was associated with low platelet counts, low lymphocyte counts, low T4:T8 ratios, and hypergammaglobulinaemia. In addition, six patients with severe haemophilia A and factor VIII inhibitors had inversed T4:T8 ratios. Patients treated exclusively with cryoprecipitate or prothrombin complex concentrates had normal T4:T8 ratios and platelet counts. The severity of the haematological and immunological abnormalities observed seems to be associated with high usage of factor VIII concentrates. Similar abnormalities have been described in patients with the acquired immune deficiency syndrome (AIDS). Prospective study of haemophiliacs is required to assess long term sequelae of factor concentrate usage, including the possible development of AIDS.     

Correlation of serum antigen and antibody concentration with clinical features in HIV infection.

Serum antigen and antibody values were studied in 164 infants and children infected perinatally with HIV. HIV antigens p17, p24, gp41, and gp120 were determined in sera by immunoblot and antigen capture assays. Lymphocyte blast transformation, serum immunoglobulins, and circulating immune complexes were also evaluated. Altogether 50 patients had HIV antigens measured: 31 (62%) patients had p17 antigen in the serum and 29 (58%) had p24 antigen present. In 19 (38%) and nine (18%) patients, respectively, gp120 and gp41 were detected. All four HIV antigens were detected in seven (14%) patients. There was a positive correlation between the concentration of each HIV sequential specimens were outcome. When sequential specimens were analysed, 120 (73%) patients had p24 antigen present. Patients with stage P2B and P2D (Centers for Disease Control classification) had the highest concentrations of p24 antigen with a mean of approximately 200 pg/ml. Altogether 70% of patients with a p24 antigen concentration of greater than 30 pg/ml eventually died or had severe clinical disease within six to 24 months. Infants under 15 months of age with a p24 antigen concentration as low as 5 pg/ml also did poorly. Increased immunoglobulins and decreases in mitogenic responses and absolute CD4+ lymphocyte counts were more prevalent in patients with raised p24 antigen. Raised concentrations of circulating immune complexes were seen in the symptomatic phase of the disease whereas in the terminal stage of the disease raised serum antigen and a decrease in circulating immune complexes and absolute CD4+ lymphocyte count were evident. Loss of p24 and/or p17 antibody as well as a decreasing ELISA optical density for HIV antibody also signalled progression of the disease.     

血小板自身抗体的流式细胞术检测与意义

目前血小板自身抗体的测定方法较为复杂,同时需要较多的血量,因此给儿科临床应用带来一定困难。本文拟应用流式细胞术建立一种简便、快捷、敏感的检测血小板相关抗体的方法。应用荧光素化的羊抗人Ｆ(ａｂ)２段ＩｇＧ抗体结合血小板表面的抗体,应用荧光素化的羊抗鼠ＩｇＧ抗体作为阴性对照。即以直接法测定血小板表面结合的ＩｇＧ。应用流式细胞术测定血小板的平均荧光强度。血小板荧光强度(ＭＦＩ)反映血小板表面ＰＡＩｇＧ的水平。测定正常人和特发性血小板减少性紫癜患儿的血小板平均荧光强度。结果显示:正常对照组的血小板平均荧光强度(ＭＦＩ)为２３．６７±９．１０(道数)。３１例ＩＴＰ组的ＭＦＩ为１０３．６３±３１．４１(道数)。ＩＴＰ病人的血小板荧光阳性率为９０%。治疗有效的病人,随血小板计数的上升,血小板荧光强度逐渐下降。因此,流式细胞术测定血小板抗体是一种快速、简便灵敏的ＰＡＩｇＧ检测方法,可用于免疫性血小板减少性紫癜的辅助诊断和疗效观察。     

Bleeding time in hemophilia A: potential mechanisms for prolongation

Prolongation of bleeding time has been previously observed in hemophilia, although no cause has been elucidated. We measured bleeding time, platelet aggregation, nucleotide release, and thromboxane B2 (TXB2), plasma 6-keto-PGF 1 alpha, platelet-associated IgG (PAIgG), and circulating immune complexes in 31 unselected patients with severe hemophilia A and in 17 controls. In 85% of patients with hemophilia A, the bleeding time was greater than 2 SD above the control level (greater than 8 minutes). Sixty-six percent of patients with hemophilia A had circulating immune complexes, and there was a striking relationship between the presence of these complexes and prolonged bleeding time. Plasma 6-keto-PGF 1 alpha levels were significantly elevated in the patient group, and correlated with bleeding time changes. Platelet aggregation and nucleotide release were normal in the patients with hemophilia, although reduced platelet TXB2 biosynthesis was noted in 26%. No correlation was demonstrated between bleeding time and impairment of platelet TXB2 formation. Seventy-two percent of the patients with hemophilia A had elevated levels of PAIgG, and an inverse relationship between PAIgG and platelet count was observed. No relationship was noted between platelet count and bleeding time. This study indicates that the majority of patients with hemophilia A have prolonged bleeding times. The close correlation between bleeding time, plasma 6-keto-PGF 1 alpha levels, and the presence of circulating immune complexes suggests a role for immune complex-mediated defects in vascular function as the basis for bleeding time prolongation.     

IgG2 deficiency in children with human immunodeficiency virus infection

Infection with the human immunodeficiency virus (HIV) induces a polyclonal B-cell activation. Despite elevated serum immunoglobulin levels, a significant deterioration of the antigen specific humoral immune response exists in most cases. We studied the influence of HIV infection on the serum levels of IgG subclasses in children. We investigated 76 children (aged 15 months to 18 years) with HIV-1-infection. Most children (88%) showed elevated serum immunoglobulin levels. IgA (87%) and IgM (74%) were more often above normal levels for age than IgG (60%). IgG subclass serum levels were significantly altered. The increase in total IgG was mainly due to a marked augmentation of the IgG1 fraction. In most cases IgG3 was simultaneously elevated. Ten children (13%) had very low IgG4 levels (<0.03 g/l). Out of 61 patients older than 2 years 8 (13%) had a profound IgG2 deficiency with normal or elevated total IgG. Four of them also had low IgG4 levels (<0.03 g/l). A correlation between IgG2 deficiency and HIV infection according to the Centres for Disease Control classification for acquired immunodeficiency syndrome could not be demonstrated (three patients with symptomatic and five with asymptomatic infection).     

Misdiagnosis of chronic thrombocytopenia in childhood

PURPOSE: Children ultimately diagnosed with nonimmune chronic thrombocytopenia are often referred to pediatric hematology clinics with a provisional diagnosis of autoimmune thrombocytopenic purpura (AITP). The authors' aim was to establish in these patients the features characterizing the mechanism of thrombocytopenia. PATIENTS AND METHODS: The authors performed a retrospective review of the case records of seven children (three boys and four girls, aged 5 months to 7 years) with misdiagnosed chronic AITP referred to a single pediatric hematology center between 1990 and 2000. RESULTS: In the seven children, the suspected diagnosis on referral was AITP and the final diagnosis was inherited thrombocytopenia. Abnormalities of platelets and/or leukocyte morphology were present in all of them. Other features suggestive of inherited thrombocytopenia included a history of familial thrombocytopenia (2/7), failure of steroids and/or intravenous immunoglobulins to raise the platelet count to normal levels (5/7), and moderate increase of Indium-111 platelet turnover in the two patients tested. Platelet-associated IgG (PaIgG) was above the normal threshold in the four children tested; the direct monoclonal antibody immobilization of platelet antigens (MAIPA) test was negative in the four children tested and the serum test was positive in two boys. Bone marrow examination revealed either a normal (4/7) or an elevated (3/7) number of megakaryocytes. CONCLUSIONS: Family history and blood cell morphology analysis in experienced hands are the first steps in discriminating AITP from inherited thrombocytopenia in children with isolated chronic thrombocytopenia. In contrast, bone marrow examination and search for specific autoantibodies using the MAIPA test are of little help. An isotopic platelet life span study, when available, should be performed before considering splenectomy to exclude the diagnosis of inherited thrombocytopenia, especially when steroids and/or IgG IV administration failed to raise the platelet count.     

Thrombocytopenia as the presenting manifestation of human T-lymphotropic virus type III infection in infants

Three infants between 8 and 9 months of age developed thrombocytopenia resulting from immune-mediated platelet destruction, as evidenced by the presence of serum antibody to platelets and elevated platelet-associated immunoglobulin G in two patients, and abundant bone marrow megakaryocytes in all patients. The patients had a satisfactory response to corticosteroid therapy, and platelet counts have remained normal during observation after therapy. All patients had serum antibody to human T-lymphotropic virus type III, and HTLV-III was isolated from the peripheral blood lymphocytes in two patients. The HTLV-III infections were presumably acquired via blood transfusions in the neonatal period; none of the patients' mothers belonged to a risk group for HTLV-III infection, and all were HTLV-III seronegative. Although thrombocytopenia was the major clinical manifestation, the patients had a number of immunologic abnormalities characteristic of HTLV-III infection; these included hyperimmunoglobulinemia, a decreased proportion of peripheral blood T cells, and a marked reduction in the proportion of peripheral blood T helper-inducer lymphocytes. We conclude that the patients had immune-mediated thrombocytopenia caused by HTLV-III infection.     

小儿特发性血小板减少性紫癜血小板相关抗体、T细胞亚群检测及其临床意义

本文对1989年9月至1995年2月收治的112例小儿特发性血小板减少性紫癜的血小板相关性抗体、T细胞亚群检测及其临床意义进行了探讨。结果表明：急、慢型无论是OKT3及OKT4+均低于正常对照组，且有显著性差异，P值均＜0．05；而OKT8+与正常对照组相比则较高，P值＜0．025。但是，急、慢两型相比均未见统计学上显差性差异。本文的检测血小板抗体lgG、IgM及IgA，显示均有所增高尤以PAIgG最明显，阳性率达85．7％，与文献报道近似。经治疗10例血小板动态变化，PAIg随着血小板的恢复均下降至正常，呈负相关.     

Neonatal alloimmune thrombocytopenia associated with anti-human platelet antigen-3a antibody

A sister and brother with neonatal alloimmune thrombocytopenic purpura (NAITP) caused by maternal anti-human platelet antigen (HPA)-3a are reported. The children had transient severe thrombocytopenia in the newborn period, and were treated with intravenous γ-globulin and platelet concentrates from random donors. Although the sister had intracranial hemorrhage on day 2 postnatally, the development of the child has been normal and no neurological sequelae have been observed. The brother only had bloody stool when the platelet count was low, and did not have severe hemorrhagic manifestations. The diagnosis of NAITP was made by the sera from the mother, which contained anti-HPA-3a antibody directed against platelets of the children. The rate of recurrence might be high in this family, because the father of the patients was found to be homozygous for the HPA-3a gene.     

Changes in laboratory features of 192 children with imported falciparum malaria treated with quinine

Little is known about changes in laboratory values of children with imported falciparum malaria. Of 192 children, 69% had parasitemia of 2% or less and 64% had platelets <150 x 10/L. In 20%, parasite counts rose within 12-24 hours of starting treatment before falling, whereas the platelet counts dropped in 45% but returned to normal levels within 5 days. Hemoglobin values were <10 g/dL in 31% at presentation and dropped in 61% at 5-21 days after treatment, but did not fall below 6.8 g/dL in any case. Blood cultures were negative in all children. Hyponatremia (n = 16), jaundice (n = 4) and hypoglycemia (n = 0) were uncommon. Thus most children presented with abnormal laboratory values, which initially worsened in a significant proportion, but none required active intervention once therapy was initiated.     

特发性血小板减少性紫癜患儿血小板生成素及其受体基因转录水 …

目的 探讨急性特发性血小板减少性减少性紫癜（ＡＴＴＰ）患儿血小板生成素（ＴＰＯ）及血小板ＴＰＯ受体ｃ－ＭＰＬ ｍＲＮＡ基因转化水平变化的意义。方法 采用ＥＬＩＳＡ法检测血清ＴＰＯ、血小板相关抗体（ＰＡＩｇＧ）水平;半定量ＲＴ－ＰＣＲ法检测外周血血小板ｃ－ＭＰＬ ｍＲＮＡ的相对量。结果 ＡＴＴＰ患儿初治时血浆ＴＰＯ水平增高,血小板ｃ－ＭＯＬ ｍＲＮＡ较低;以大剂量甲基强的松龙冲击治疗后,位随血小板计     

Humoral immunity in children with proven bronchiectasis, bronchial deformations and chronic bronchitis

In 70 children with defined chronic chest disease, immunoglobulins, IgG subclass levels and antibody concentrations specific for Haemophilus influenzae b (Hib), and pneumococcal antigen, were related to disease severity. Bronchological examinations revealed 30 children with chronic bronchitis, 21 with bronchial deformations and 19 with bronchiectasis. Of the 70 children 12 (17.1%) showed an underlying immunodeficiency. The commonest finding was an IgG subclass deficiency, 7 were IgG₂ and 1 IgG₃ deficient, followed by IgA deficiency in 3 patients. All patients had normal IgG and IgM levels except one who had immunodeficiency with elevated IgM. Pneumococcal antibody levels were found to increase between patient groups in the order healthy children < chronic bronchitis < bronchiectasis < bronchial deformations (p < 0.01), but this was not the case for Hib antibodies. We found no selective deficiency of pneumococcal and Hib antibodies in our patients. Pathogens were detected in bronchial cultures from 10% of patients with chronic bronchitis, 33% of those with bronchial deformations and in 63% with bronchiectasis. This increase (p < 0.01) reflects a more severe inflammation of the respiratory tract in such patients. However, immunodeficiencies were equally distributed between patient groups. We conclude that only a subgroup of children with chronic chest disease have an underlying immunodefiency, but most patients (83%) do synthesize normal or even high antibodies in the presence of a bacterial load.     

Intramuscular anti‐D in chronic immune thrombocytopenia children with severe thrombocytopenia

Nine patients with chronic immune thrombocytopenia and platelet counts <20 × 10⁹/L, with a median age of 7.8 (3.8–15.5) years, received three phases of 10 mcg/kg/dose of intramuscular anti‐D. Phase 1 was anti‐D daily for 5 days, followed by phase 2, anti‐D weekly for 12 weeks and withheld when platelet counts ≥20 × 10⁹/L, and then phase 3 was anti‐D once every 2 weeks for 24 weeks. According to the International Working Group criteria, in phase 1, 66.7% of patients responded to the treatment. In phases 2 and 3, 11.1% (0–41.7%) and 7.7% (0–33.3%) of total episodes of follow up, respectively, responded to the treatment. Therefore, intramuscular anti‐D given at a dose of 10 mcg/kg for 5 days is an alternative method to raise platelet counts in chronic immune thrombocytopenia children with severe thrombocytopenia where the intravenous form of anti‐D is not available.