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.     

不同剂型、剂量的肾上腺皮质激素治疗小儿特发性血小板减少性紫癜疗效观察

三种不同剂型、剂量的肾上腺皮质激素治疗小儿特发性血小板减少性紫癜 ,结果表明 :对出血症状的控制速度 ,地塞米松冲击组优于甲基强的松龙冲击组 ,也优于强的松组 ;血小板计数的升高幅度也是冲击组优于常规剂量组 ,差异有显著意义 ;治疗后 PAIg G的下降在冲击治疗组优于常规剂量组。建议 :对于急性出血症状明显、且 PAIg G增高也较明显的患儿 ,应首选大剂量糖皮质激冲击治疗。     

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.     

Thrombocytic alpha-delta-storage-pool-disease: shortening of bleeding time after infusion of 1-desamino-8-D-arginine vasopressin]

BACKGROUND: The synthetic vasopressin derivate desmopressin (1-desamino-8-D-arginine vasopressin) has been reported to shorten the bleeding time in patients with hemophilia A, von Willebrand's disease and several functional platelet disorders. In addition to substitution of platelets, vasopressin is therefore used to prevent bleeding complications. CASE: We report the case of a 14-year-old female patient with prolonged bleeding time due to the rare thrombocytic alpha-delta-storage-pool-disease. When normal donor platelet substitution alone was ineffective, bleeding time was normalised after infusion of desmopressin and elective wisdom-tooth extraction was performed without significant postoperative bleeding. DISCUSSION: Infusion of desmopressin appears to be effective in shortening bleeding time in thrombocytic storage-pool-disease. Its use could prevent bleeding complications after trauma and surgical interventions and may possibly help to spare the need for platelet concentrates.     

Prostanoid production in umbilical arteries from preterm and term deliveries perfused in vitro

The endogenous prostanoid production in human umbilical arteries from gestational stages between 192 and 290 days was investigated using an in vitro perfusion technique. The outflow concentrations of prostacyclin and thromboxane (measured as their stable metabolites 6-keto-PGF1 alpha and TXB2), PGE2 and PGF2 alpha were determined by RIA-methods. The production of all four prostanoids was found to increase with the duration of pregnancy. The formation of prostacyclin was always dominating, followed by PGE2, PGF2 alpha and thromboxane.     

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.     

Role of complement in immune or idiopathic thrombocytopenic purpura

The clinical course of immune or idiopathic thrombocytopenic purpura (ITP) is variable, suggesting different mechanisms for the decreased platelet count. The complement factors C3 and C4 have been detected on platelets, both alone and in association with immunoglobulin G (IgG), and a reduced platelet survival time has been described. Platelets have the capacity to interact with the complement system since they have both complement receptors and complement regulatory proteins on their cell membranes. The membrane attack complex (C5b-9) induced by antiplatelet antibodies generates platelet microparticles in a concentration-dependent manner. A marked variation in resistance to this phenomenon has been demonstrated between individuals and between men and women. These platelet microparticles seem to retain their biological role in haemostasis. Platelets also appear to play a role in the processing of immune complexes. Immunoglobulins and complement factors are found in several clinical situations where circulating immune complexes are expected. Furthermore, human platelets bind immune complexes in vitro and the reaction can be blocked by antireceptor antibodies to immunoglobulins and complement. These findings raise a number of questions about the role of complement in the pathophysiology of ITP.     

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.     

Effect of homocysteine and homocystine on platelet and vascular arachidonic acid metabolism

Normal hemostasis depends in part on the balance achieved between proaggregatory and prothrombotic platelet thromboxane A2, measured as its stable end-product thromboxane B2 (TXB2), and vascular prostacyclin (PGI2), which inhibits platelet aggregation and is antithrombotic. Cystathionine-beta-synthase deficiency is characterized by a high frequency of thromboembolic disease. We therefore studied, in vitro, the effects of homocysteine and related compounds on platelet TXB2 and vascular PGI2 formation. In paired samples of platelet rich plasma, which had been preincubated with L-homocystine (1 mM), mean production of the two platelet cyclooxygenase products, TXB2 and 12-hydroxy-5, 8,10-heptadecatrienoic acid increased significantly from control levels [13.6% +/- 1.9 to 19.8% +/- 2.1 (P less than 0.02) TXB2 and 29.8% +/- 4.2 to 39.4% +/- 4.1 (P less than 0.01) HHT]. In the presence of D,L-homocysteine (1 mM), mean TXB2 and 12-hydroxy-5,8,10-heptadecatrienoic acid production was also significantly increased [12.7% +/- 1.5 to 16.9% +/- 1.5 (P less than 0.01) TXB2 and 27% +/- 4 to 31% +/- 4.1 (P less than 0.02) HHT]. Cystine, cysteine, or methionine (1 mM) did not have similar effects in this test system. Homocysteine and homocystine were without effect on the synthesis of vascular PGI2 by umbilical artery segments [control, 0.22 +/- 0.03 to 0.21 +/- 0.03 ng/mg with D,L-homocysteine and 0.20 +/- 0.04 control to 0.19 +/- 0.04 ng/mg with D,L-homocystine]. A homocyst(e)ine-induced increase in platelet thromboxane production in the absence of an increase in vascular prostacyclin, if present in vivo, may contribute to the vascular thromboses characteristic of human homocystinemias (homocystinurias).     

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.     

Soluble immune complexes, acute phase proteins and E-rosette inhibitory substance in sera of malnourished children

The percentage of circulating E-rosetting lymphocytes and the presence of serum E-rosette inhibitory substance were determined in 58 marasmic, 13 kwashiorkor and 22 well-fed children. The blood levels of soluble immune complexes and some acute phase proteins were also measured. The percentage of E-rosetting lymphocytes was significantly higher in the well-fed than in the malnourished children. The presence of the inhibitory substance in serum correlated with depressed levels of circulating mean percentage E-rosetting lymphocytes. Elevation in the level of soluble immune complexes was observed to correlate closely with the presence of serum E-rosette inhibitory substance and with a diminished percentage of E-rosetting lymphocytes. There was no significant correlation between the percentage of circulating E-rosetting lymphocytes and the serum alpha 1 antitrypsin, alpha 2 macroglobulin or C-reactive protein levels. It is suggested that at high serum concentrations soluble immune complexes may bind selectively to human T lymphocytes in vivo, thereby inhibiting the latter's ability to form E-rosettes in vitro.     

Platelet-Associated IgG in Pediatric HIV Infection

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.     

THE EFFECT OF ACETYLSALICYLIC ACID ON PLATELET FUNCTION IN CYANOTIC CONGENITAL HEART DISEASE

ABSTRACT. Goldschmidt, B., Serland, S. J. and Bjernstad, P. G. (Second Department of Paediatrics, Semmelweis University Medical School, Budapest, Hungary; Institute for Thrombosis Research and Department of Paediatrics, Rikshospitalet, Oslo, Norway). The effect of acetylsalicylic acid on platelet functions in cyanotic congenital heart disease. Acta Paediatr Scand, 63: 869, 1974.—Children with cyanotic congenital heart disease (CCHD) are susceptible to thromboembolic complications. The pharmacologic inhibition of platelet function may be efficacious in the prophylaxis of thrombosis. The authors have studied the platelet count, Ivy and Duke bleeding time, platelet adhesiveness in vivo and in vitro , thrombelastogram, spontaneous platelet aggregability and platelet aggregation induced by collagen, ADP and adrenaline in children with CCHD before and afier ingestion of acetylsalicylic acid (ASA) or placebo. Before treatment, some of the patients had thrombocytopenia, prolonged Ivy bleeding time, increased platelet adhesiveness in vivo and in vitro and increased spontaneous platelet aggregation. In a placebo group, there was no significant change in the pre- and post-treatment values of the investigated indices. After ASA treatment there was no significant change in the platelet counts, Duke bleeding time and thrombelastogram. There was a significant prolongation of Ivy bleeding time, decrease of in vivo and in vitro platelet adhesiveness and normalization of the spontaneous platelet aggregation. ASA inhibited the secondary wave of aggregation induced by small doses of ADP or adrenaline, and decreased aggregation induced by collagen. These data suggest that ASA may be suitable for prevention of thromboembolic complications in CCHD.     

Plasma prostacyclin from birth to adolescence.

The plasma concentration of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable hydration product of prostacyclin, was measured by radioimmunoassay in 111 healthy children aged between 1 day and 16 years and in 21 healthy adults aged between 21 and 72 years. The 6-keto-PGF1 alpha levels in children up to age 16 years were higher than those in adults. During the first 4 days of life the plasma concentrations of 6-keto-PGF1 alpha in term infants were higher (P less than 0.05) than the respective levels in preterm infants. There was no difference between the 6-keto-PGF1 alpha levels measured simultaneously in umbilical arterial and peripheral venous plasma in 7 newborn infants. Maternal pre-eclampsia or epidural analgesia during labour, mode of delivery, birthweight, or sex of the infants were not related to the plasma 6-keto-PGF1 alpha levels on the first day of life. High levels of vasodilatory and anti-aggregatory prostacyclin during the first days of life may play a role in the postnatal adaptation of the circulation and platelet function.     

State of microcirculation homeostasis in children with rheumatism

Microcirculatory homeostasis was studied in 107 children suffering from rheumatic fever. Conjunctival microcirculation and platelet aggregation were examined. The content of circulating immune complexes and medium-size molecules was measured in the blood. Microcirculation was investigated in 137 healthy children aged 3 to 15 years, making up a control group. Comprehensive investigation of microcirculation in children suffering from rheumatic fever enables one to define the activity of the rheumatic process at the early times of the illness and to ensure timely administration of adequate antirheumatic therapy.     

Occurrence of circulating immune complexes in beta-thalassaemia major.

The presence of circulating soluble immune complexes and the level of complement were investigated in sera from 21 patients with beta-thalassaemia major, including both splenectomised and nonsplenectomised patients. A high level of immune complexes was found in half of these cases. Reduced complement levels were seen less frequently. There was no correlation between the presence of circulating immune complexes, decreased complement levels, and thpresence or absence of the spleen. The level of immune complexes increased with the age ofthe individual, i.e. with the duration of the disease.     

PLATELET FUNCTIONS IN CHILDREN WITH CONGENITAL HEART DISEASE

Abstract. Goldschmidt, B. (Second Department of Paediatrics, Semmelweis Medical University, Budapest, Hungary). Platelet functions in children with congenital heart disease. Acta Paediat Scand, 63 271, 1974.–Examinations of platelet functions (bleeding time, capillary resistance, clot retraction, thrombocyte adhesiveness in vitro and in vivo, spontaneous platelet aggregation, ADP and collagen induced platelet aggregation) were performed in children with CHD. In the cases with acyanotic heart disease (30 cases) the platelet functions were normal. The majority of cases with cyanotic CHD (35 cases) are thrombocytopenic. In these cases protracted bleeding time, increased capillary fragility and reduced clot retraction may be 'observed. The pathologic symptoms are connected with the low number of platelets. In patients with cyanotic CHD the platelet adhesiveness shows in vitro and in vivo a statistically significant increase. In one third of cases, platelet aggregation is also increased in cyanotic patients. Following the administration of ADP and collagen the aggregation shows a normal course.     

Platelet aggregation in iron deficiency anemia

In-vitro platelet aggregation with ADP, adrenaline and collagen was studied in pediatric patients with iron deficiency before and after iron therapy, and in normal controls. Hyporeactivity of platelets to all agonists was seen in the untreated patients. This returned to normal following correction of anemia by iron therapy. There was a significant correlation between hemoglobin or serum iron and transferrin saturation on the one hand, and parameters of platelet aggregation on the other (P<0.001). Results of zero order correlation coefficient however, showed that platelet reactivity was actually dependent on the hemoglobin levels rather than the iron parameters per se. This may explain the prolonged bleeding time in patients with iron deficiency, particularly those associated with thrombocytopenia. Anemic individuals may be protected against thrombotic disorders due to this reduced platelet reactivity.     

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??Objective analyze the current status of bone metabolism and bone mineral density??BMD?? in moderate/severe hemophilia children??to provide data for improving the life quality of Chinese children with hemophilia. Methods Bone metabolism and BMD data were analyzed for 28 cases of moderate/severe hemophilia children diagnosed in Hemophilia Center of Beijing Children Hospital from October 2014 to February 2015. Results ??1??The median age of 28 cases of hemophilia children was 12.9??range 6 to 18 years?? years old??hemophilia A 22 was in cases??78.6%????hemophilia B 6 cases??21.4%???? Severe hemophilia children was in 19 cases??67.9%????moderate hemophilia children 9 cases??32.1%??. The mean of BMD was ??151.86±25.93?? g/L??which was significantly lower than the normal children???191.48±20.36?? g/L???P??0.05. There was no relationship in Age??time of the first bleeding, as well as frequency of bleeding with BMD??P??0.05??. But significant correlation was found between BMD and outdoor activities/school activities participation??P??0.0002 and 0.0016??. Conclusion BMD of hemophilia children without bone metabolic abnormalities is significantly lower than that of the normal children in China. Reducing joint bleeding and increasing the outdoor activities??rather than supplement calcium blindly will be the key point to improve the life quality of hemophilia children.     

Sustained engraftment post bone marrow transplant despite anti-platelet antibodies in Glanzmann thrombasthenia

BACKGROUND: Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti-platelet antibodies. PATIENTS AND RESULTS: Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry. All patients had severe bleeding requiring multiple red blood cell transfusions. One patient received an unrelated donor transplant and two received matched sibling donor transplants following conditioning therapy with busulfan, cyclophosphamide, and fludarabine. Two patients developed an anti-platelet antibody, treated in one with intravenous immune globulin (IVIG). Engraftment of white blood cells and platelets was achieved on day +13 to +14 and +17 to +25, respectively. Complete donor chimerism and GPIIb/IIIa+ platelets are sustained at +22 to +30 months post transplant. CONCLUSIONS: In summary, patients with GT and history of severe hemorrhage can be cured with BMT, but the presence of anti-platelet antibodies should be sought and platelet transfusions minimized prior to transplant. IVIG may be helpful in cases of refractory immune thrombocytopenia related to anti-platelet antibodies. Improvement in transplant-related complications with current transplant regimens allows consideration of BMT for life-threatening non-malignant disorders such as GT.