[Clinical effect of gamma globulin pulse therapy for abdominal Henoch-Schönlein purpura in children].

OBJECTIVE: To study the clinical effect of high-dose gamma globulin pulse therapy for abdominal Henoch-Schönlein purpura (HSP). METHODS: Thirty-three children with abdominal HSP were randomly assigned to dexamethasone group (15 children) and gamma globulin group (18 children). The children in the dexamethasone group were treated with dexamethasone and conventional treatment, and those in the gamma globulin group were treated with high-dose gamma globulin pulse therapy in addition to the conventional treatment. Clinical outcome and recurrence rate were observed in both groups. RESULTS: Compared with the dexamethasone group, the gamma globulin group had a significantly shorter onset time of rash, a significantly shorter time to complete regression of rash, a significantly shorter time to abdominal pain remission, and a significantly shorter time to disappearance of bloody stool, as well as comparable time to vomiting remission and length of hospital stay. The gamma globulin group had a significantly higher response rate than the dexamethasone group (95% vs 65%; P<0.05) and a significantly lower recurrence rate within 6 months than the dexamethasone group (5.6% vs 33.3%; P<0.05). CONCLUSIONS: High-dose gamma globulin pulse therapy has a marked clinical effect in the treatment of abdominal HSP. It is safe and reliable and has a low recurrence rate, and therefore, it holds promise for clinical application.

Use of Gammaglobulin to Lower Elevated Natural Killer Cells in Patients with Recurrent Miscarriage.

OBJECTIVE: To evaluate the effectiveness of intravenous immunoglobulin (IVIG) in patients presenting with recurrent miscarriage and abnormally elevated natural killer (NK) cells. STUDY DESIGN: This retrospective patient controlled evidence level II-2 pilot study was conducted at Cohen Center, P.A., Medical City Dallas Hospital. Ninety women with a history of recurrent miscarriage (average, 5) and elevated NK cells were retrospectively evaluated to document the outcome of their treatment with IVIG. RESULTS: Of 90 women with elevated NK cells who received IVIG treatment, 78 (86.7%) became pregnant. Sixty-four (82.0%) of those pregnancies had a successful viable outcome. Fourteen (18.0%) gestations ended as first trimester miscarriages. CONCLUSION: We conclude at evidence level II-2 that, with adequate precautions, low-dose IVIG therapy is safe and effective for women with immunologic abortion and documented abnormally elevated NK cells.

Uso de la gammaglobulina intravenosa y sus efectos en la mortalidad por sepsis en niños / Use of Intravenous Gama Globulin and its effects on children mortality for sepsis

Se realizó una revisión sistemática sobre el uso de inmunoglobulina intravenosa y su efecto sobre la mortalidad en el niño menor de un año. Se analizaron artículos originales y revisiones sistemáticas realizadas en los últimos años acerca del tema; se incluyeron artículos originales publicados en los años 2002 al 2011 y las revisiones sistemáticas publicadas en los años 2007 al 2011, que resultaron en total siete. Se concluye que no existe un consenso en la prescripción de inmunoglobulina intravenosa en el tratamiento de la sepsis y aunque no existe reducción significativa de la mortalidad, se evidencia un mayor número de vidas salvadas en el grupo de pacientes con este tratamiento (AU)

A systematic revision about the use of intravenous gamma globulin, and its effect on mortality of children under one year old, was carried out. Diverse original articles and systematic revisions developed in the last years were analyzed; the original articles published from 2002 to2011 and the seven systematic revisions published from 2007 to2011 were included. It is concluded that there is no consensus regarding the prescription of intravenous immune globulin to treat sepsis, and although there is no significant reduction of mortality, it is evident that a greater amount of patients saved their lives with this treatment (AU)

Pulmonary function in children and young adults with ataxia telangiectasia.

BACKGROUND: Pulmonary disease contributes to significant morbidity and mortality in people with ataxia telangiectasia (A-T). To determine the association between age and lung function in children and young adults with A-T and to identify factors associated with decreased lung function, pulmonary function tests were performed in 100 consecutive people with A-T. METHODS: Children and adults ranging from 6 to 29 years of age and with the diagnosis of A-T were recruited, and underwent pulmonary function tests. RESULTS: The mean forced vital capacity % predicted (FVC %) in the population was 56.6 ± 20.0. Males and females between 6 and 10 years of age had similar pulmonary function. Older females were found to have significantly lower FVCs % than both older males (P < 0.02) and younger females (P < 0.001). The use of supplemental gamma globulin was associated with significantly lower FVC %. A modest correlation was found between higher radiation-induced chromosomal breakage and lower FVC % in males. No significant change in FVC % was found in a subset of subjects (n = 25) who underwent pulmonary function testing on two or more occasions over an average of 2 years. CONCLUSION: In children and young adults with A-T, older females and people who required supplemental gamma globulin had significantly lower lung function by cross-sectional analysis. Stable lung function is possible over a 2-year period. Recognition of groups who are at higher risk for lower pulmonary function may help direct care and improve clinical outcomes in people with A-T.

[Adverse events in 1395 infusions with different intravenous gammaglobulin products]. / Eventos adversos en 1395 infusiones con diferentes preparados de gammaglobulina intravenosa.

The processes of isolation and sterilization of intravenous gamma globulin (IVIG) affect the end product characteristics and, therefore, its tolerability. Different products have different incidences of adverse reactions. The aim of this study was to quantify the immediate adverse events (AE) caused by the different IVIG preparations. We analyzed 1 395 infusions in 28 patients, with a median of 32.5 per subject (range 2-214), using six different IVIG preparations, with an average dose 40.3 ± 8.3 g. One thousand and thirty-one infusions were analyzed retrospectively and 364 prospectively. Patients used a mean of 2.68 ± 1.8 different IVIGs, with a median of 2 (range 1-6) per person. The number of trademarks used was related to the number of infusions received, r = 0.73. AE presented in 24 (2.3%) of 1 031 infusions retrospectively analyzed, affecting 11 of 23 patients enrolled, with a mean of 2.18 ± 1.08 AE per subject. Of 24 patients and 364 infusions prospectively analyzed, AE were observed in 14 patients and in 32 (7.2%) procedures. Twenty-four (42.9%) of 56 AE were mild, 31 (55.5%) moderate and one (1.8%) severe. The infusion rate was 9.04 ± 6 g/h for those presenting AE vs. 10.6 ± 4.6 g/h for those who did not (p = 0.31, NS). The incidence, severity and proportion of patients with AE for each brand of IVIG were very different from each other. This information should be taken into account when selecting the IVIG to be used.

Eventos adversos en 1395 infusiones con diferentes preparados de gammaglobulina intravenosa / Adverse events in 1395 infusions with different intravenous gammaglobulin products

Los procesos de aislamiento y esterilización de la gammaglobulina endovenosa (IVIG) afectan las características del producto terminado y, por lo tanto, su tolerabilidad. Distintos productos tienen diferentes incidencias de reacciones adversas. Este trabajo cuantifica los eventos adversos (EA) inmediatos provocados por distintas preparaciones de IVIG. Analizamos 1395 infusiones en 28 pacientes, con una mediana de 32.5 por sujeto (rango 2-214), utilizando seis preparados distintos de IVIG, con una dosis total promedio de 40.3 ± 8.3 g. Analizamos retrospectivamente 1 031 infusiones y 364 prospectivamente. Los pacientes utilizaron una media de 2.68 ± 1.8 IVIG diferentes, con una mediana de 2 (rango 1-6) por persona. El número de marcas comerciales utilizadas se relacionó con el número de infusiones recibidas, r = 0.73. En 24 (2.3%) de 1031 infusiones analizadas en forma retrospectiva se registraron EA que afectaron a 11 de los 23 casos incluidos, con una media de 2.18 ± 1.08 EA por afectado. De 24 pacientes y de 364 infusiones prospectivas, en 14 pacientes y en 32 (7.2%) procedimientos se observaron EA. Veinticuatro (42.9%) de 56 EA fueron leves, 31 (55.5%) moderados y uno (1.8%) fue grave. La velocidad de infusión fue de 9.04 ± 4.6 g/h para las que presentaron EA vs. 10.6 ± 4.6 g/h para las que no (p = 0.31). La incidencia, la gravedad y la proporción de pacientes afectados con EA para cada marca comercial de IVIG fueron muy diferentes entre sí. Esta información debe ser tomada en cuenta en el momento de selección de la IVIG a utilizar.

The processes of isolation and sterilization of intravenous gamma globulin (IVIG) affect the end product characteristics and, therefore, its tolerability. Different products have different incidences of adverse reactions. The aim of this study was to quantify the immediate adverse events (AE) caused by the different IVIG preparations. We analyzed 1 395 infusions in 28 patients, with a median of 32.5 per subject (range 2-214), using six different IVIG preparations, with an average dose 40.3 ±8.3 g. One thousand and thirty-one infusions were analyzed retrospectively and 364 prospectively. Patients used a mean of 2.68 ±1.8 different IVIGs, with a median of 2 (range 1-6) per person. The number of trademarks used was related to the number of infusions received, r = 0.73. AE presented in 24 (2.3%) of 1 031 infusions retrospectively analyzed, affecting 11 of 23 patients enrolled, with a mean of 2.18 ± 1.08 AE per subject. Of 24 patients and 364 infusions prospectively analyzed, AE were observed in 14 patients and in 32 (7.2%) procedures. Twenty-four (42.9%) of 56 AE were mild, 31 (55.5%) moderate and one (1.8%) severe. The infusion rate was 9.04±4.6 g/h for those presenting AE vs. 10.6±4.6 g/h for those who did not (p = 0.31, NS). The incidence, severity and proportion of patients with AE for each brand of IVIG were very different from each other. This information should be taken into account when selecting the IVIG to be used.

Eventos adversos en 1395 infusiones con diferentes preparados de gammaglobulina intravenosa / Adverse events in 1395 infusions with different intravenous gammaglobulin products

Los procesos de aislamiento y esterilización de la gammaglobulina endovenosa (IVIG) afectan las características del producto terminado y, por lo tanto, su tolerabilidad. Distintos productos tienen diferentes incidencias de reacciones adversas. Este trabajo cuantifica los eventos adversos (EA) inmediatos provocados por distintas preparaciones de IVIG. Analizamos 1395 infusiones en 28 pacientes, con una mediana de 32.5 por sujeto (rango 2-214), utilizando seis preparados distintos de IVIG, con una dosis total promedio de 40.3 ± 8.3 g. Analizamos retrospectivamente 1 031 infusiones y 364 prospectivamente. Los pacientes utilizaron una media de 2.68 ± 1.8 IVIG diferentes, con una mediana de 2 (rango 1-6) por persona. El número de marcas comerciales utilizadas se relacionó con el número de infusiones recibidas, r = 0.73. En 24 (2.3%) de 1031 infusiones analizadas en forma retrospectiva se registraron EA que afectaron a 11 de los 23 casos incluidos, con una media de 2.18 ± 1.08 EA por afectado. De 24 pacientes y de 364 infusiones prospectivas, en 14 pacientes y en 32 (7.2%) procedimientos se observaron EA. Veinticuatro (42.9%) de 56 EA fueron leves, 31 (55.5%) moderados y uno (1.8%) fue grave. La velocidad de infusión fue de 9.04 ± 4.6 g/h para las que presentaron EA vs. 10.6 ± 4.6 g/h para las que no (p = 0.31). La incidencia, la gravedad y la proporción de pacientes afectados con EA para cada marca comercial de IVIG fueron muy diferentes entre sí. Esta información debe ser tomada en cuenta en el momento de selección de la IVIG a utilizar.(AU)

The processes of isolation and sterilization of intravenous gamma globulin (IVIG) affect the end product characteristics and, therefore, its tolerability. Different products have different incidences of adverse reactions. The aim of this study was to quantify the immediate adverse events (AE) caused by the different IVIG preparations. We analyzed 1 395 infusions in 28 patients, with a median of 32.5 per subject (range 2-214), using six different IVIG preparations, with an average dose 40.3 ±8.3 g. One thousand and thirty-one infusions were analyzed retrospectively and 364 prospectively. Patients used a mean of 2.68 ±1.8 different IVIGs, with a median of 2 (range 1-6) per person. The number of trademarks used was related to the number of infusions received, r = 0.73. AE presented in 24 (2.3%) of 1 031 infusions retrospectively analyzed, affecting 11 of 23 patients enrolled, with a mean of 2.18 ± 1.08 AE per subject. Of 24 patients and 364 infusions prospectively analyzed, AE were observed in 14 patients and in 32 (7.2%) procedures. Twenty-four (42.9%) of 56 AE were mild, 31 (55.5%) moderate and one (1.8%) severe. The infusion rate was 9.04±4.6 g/h for those presenting AE vs. 10.6±4.6 g/h for those who did not (p = 0.31, NS). The incidence, severity and proportion of patients with AE for each brand of IVIG were very different from each other. This information should be taken into account when selecting the IVIG to be used.(AU)

Eventos adversos en 1395 infusiones con diferentes preparados de gammaglobulina intravenosa. / [Adverse events in 1395 infusions with different intravenous gammaglobulin products].

The processes of isolation and sterilization of intravenous gamma globulin (IVIG) affect the end product characteristics and, therefore, its tolerability. Different products have different incidences of adverse reactions. The aim of this study was to quantify the immediate adverse events (AE) caused by the different IVIG preparations. We analyzed 1 395 infusions in 28 patients, with a median of 32.5 per subject (range 2-214), using six different IVIG preparations, with an average dose 40.3 ± 8.3 g. One thousand and thirty-one infusions were analyzed retrospectively and 364 prospectively. Patients used a mean of 2.68 ± 1.8 different IVIGs, with a median of 2 (range 1-6) per person. The number of trademarks used was related to the number of infusions received, r = 0.73. AE presented in 24 (2.3

) of 1 031 infusions retrospectively analyzed, affecting 11 of 23 patients enrolled, with a mean of 2.18 ± 1.08 AE per subject. Of 24 patients and 364 infusions prospectively analyzed, AE were observed in 14 patients and in 32 (7.2

) procedures. Twenty-four (42.9

) of 56 AE were mild, 31 (55.5

) moderate and one (1.8

) severe. The infusion rate was 9.04 ± 6 g/h for those presenting AE vs. 10.6 ± 4.6 g/h for those who did not (p = 0.31, NS). The incidence, severity and proportion of patients with AE for each brand of IVIG were very different from each other. This information should be taken into account when selecting the IVIG to be used.

Acute cerebellar infarction associated with intravenous gammaglobulin treatment in idiopathic thrombocytopenic purpura.

Intravenous immunoglobulins (IVIGs) are used for a variety of immunologic and hematologic disorders. Hemorheologic alteration or the rapid increase of platelet counts by IVIG administration can cause thrombotic adverse events. We present a 58-year-old woman with a previous diagnosis of idiopathic thrombocytopenic purpura who developed cerebellar infarction immediately after IVIG treatment. We discuss a possible role of IVIG in cerebral ischemia and management strategies.

The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature.

Anaphylactic reactions to immunoglobulin infusions in immunodeficient patients with undetectable IgA have been attributed in several reports to IgG or IgE anti-IgA antibodies. However, other reports have not supported an association between such antibodies and the development of severe reactions. We have reviewed the articles reporting reactions to immunoglobulin products in IgA-deficient patients, as well as those describing the presence of such antibodies in the absence of reactions to infusions. A variety of factors might influence the association of adverse reactions with anti-IgA antibodies, including the serum concentration and isotype (IgG or IgE) of the anti-IgA antibody, its specificity (class or subclass specific), the method of measurement, and the IgA content of the gamma globulin infusion and its route of administration. The role of anti-IgA antibodies in causing anaphylaxis in IgA-deficient patients receiving gamma globulin therapy is still controversial. Larger (multicenter) studies are needed to further evaluate this association.

Intravenous gammaglobulin-associated renal impairment reported to the FDA: 2004 - 2009.

Since the 1999 US Food and Drug Administration (FDA) warning of renal failure/dysfunction associated with intravenous gammaglobulin (IVIg), there has been a movement towards developing safer, more convenient formulations. Until now, the scope of renal failure associated with IVIg, has not been well described. The FDA Adverse Event Reporting System (AERS) from 2004 through 2009 was examined for renal impairment reactions due to IVIg and associated demographic features, comorbidities and indications. Anaphylaxis cases associated with IVIg administration were used as a comparison group. There were 90 renal impairment cases associated with IVIg administration. Neuromuscular disorders (33/37%) and hematologic disorders (32/36%) were the predominant treatment indications. When reported anaphylaxis versus renal impairment due to IVIg was examined as a binary outcome in logistic regression modeling, renal impairment was predicted by sucrose presence, increasing age and non-hypogammaglobulinemic indications. Of the 34 hemodialysis cases, the excipient was known in 28 and all but 1 consisted of sucrose. IVIg containing sucrose was used in 33 of 48 nonhemodialysis cases. More hemodialysis cases also had diabetes mellitus. When the interval between renal impairment and the first IVIg infusion was determined, the renal impairment was reported by the second day in 43.3% of cases, and between 3 and 5 days in 41.7% of cases. Despite an evolution in clinical usage and formulations, renal impairment after IVIg administration continues to be reported. Sucrose as the excipient in IVIg plays a major role, but other factors are also important. These findings have implications in the management of patients treated with IVIg.

Variant Creutzfeldt-Jakob disease and exposure to fractionated plasma products.

BACKGROUND: The risk to public health of onward transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion and plasma product administration is of on-going concern, particularly with the recent reported detection of abnormal prion protein in a person with haemophilia. OBJECTIVES: To describe the history of fractionated plasma product exposure in clinical cases of vCJD in the UK. METHODS: Through examination of records held at the National CJD Surveillance Unit (from relatives, general practices and hospitals). RESULTS: Nine out of 168 UK vCJD cases had a history of receipt of fractionated plasma products on 12 different occasions (1 pre-vCJD risk in 1970, the remaining between 1989-1998). According to the UK CJD Incident Panel risk assessment criteria, 11 were low-risk products and one was low or medium risk. CONCLUSION: It is unlikely that any of the UK vCJD clinical cases to date were infected through exposure to fractionated plasma products. However, the possibility that such transmission may result in vCJD cases in the future cannot be excluded.

Immunoglobulins for preventing hepatitis A.

BACKGROUND: Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention. OBJECTIVES: To assess the beneficial and harmful effects of the pre- and post-exposure prophylaxis with immunoglobulins for preventing hepatitis A. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, The Chinese Biomedical Database, and Science Citation Index Expanded for trials until October 2008. In addition, we read through reference lists of the identified publications and handsearched three journals. SELECTION CRITERIA: Randomised clinical trials on immunoglobulin prophylaxis for preventing hepatitis A, irrespective of blinding, publication status, or language. DATA COLLECTION AND ANALYSIS: Data were extracted by two authors and verified by a third author. Results were presented as relative risks (RR) with 95% confidence intervals (CI). The primary outcome was occurrence of hepatitis A (infectious hepatitis). MAIN RESULTS: We included 13 trials with 567,476 participants randomised to pre- or post-exposure prophylaxis. The trials had high risk of bias. The trials were heterogeneous in terms of study setting, participants, interventions, and outcome measures. Our meta-analysis with six randomised trials showed that immunoglobulins, when used for pre-exposure prophylaxis, significantly reduced the number of adult patients with hepatitis A at 6 to 12 months (1020/286503 versus 761/134529; RR 0.53; 95% CI 0.40 to 0.70; random-effects model) in comparison with no intervention or inactive control. Four trials showed a similar effect in children aged 3 to 17 at 6 to 12 months follow-up (917/210822 versus 677/78960; RR 0.45; 95% CI 0.34 to 0.59). Comparing different doses of immunoglobulins, higher dosage was generally more effective than lower dosage (1.5 ml better than 0.75 ml and 0.75 ml better than 0.1 ml) in preventing hepatitis A. No significant systemic adverse events were reported. One trial showed that immunoglobulin was more effective than placebo for post-exposure prophylaxis. It appeared that there was no significant difference between immunoglobulins and inactivated hepatitis A vaccine in seroconversion to hepatitis A vaccine antibodies at four weeks (RR 1.16; 95% CI 0.98 to 1.38), but immunoglobulins were significantly less effective than vaccine regarding antibody levels at 8, 12, or 24 weeks. AUTHORS' CONCLUSIONS: Immunoglobulins seem to be effective for pre-exposure and post-exposure prophylaxis of hepatitis A. However, caution is warranted for the positive findings due to the limited number of trials, year of conductance, and risk of bias. Conductance of rigorous trials will be justifiable.

Long-term effects of fetal and neonatal alloimmune thrombocytopenia and its antenatal treatment on the medical and developmental outcomes of affected children.

Alloimmune thrombocytopenia (AIT) is characterized by severe thrombocytopenia, usually diagnosed after birth, which may result in intracranial hemorrhage (ICH) in as many as 20% of cases. The course of AIT typically worsens in subsequent pregnancies. Administration to mother of intravenous gammaglobulin (IVIG) and/or corticosteroids to increase the fetal platelet counts of a subsequent affected fetus is widely used to avoid ICH. The objective of this study was to evaluate the long-term effects of AIT and its antenatal treatment on the medical and developmental outcomes of affected children. Seventy-one pairs of untreated (older) and antenatally treated (younger) siblings with AIT were compared. A medical questionnaire and the Behavioral Assessment System for Children (BASC) were completed over the telephone by mothers. In this sample, birth platelet counts of treated fetuses were significantly higher than those of the untreated fetuses. Treated children were born at significantly lower gestational ages and with significantly lower birthweights than untreated children. No treated child suffered a perinatal ICH compared with 12 untreated siblings. Treated siblings also had fewer vision problems (three versus 14 in the untreated group). Children treated as fetuses received higher scores on the BASC Adaptive Skills Composite than their untreated siblings. The antenatal regimen of IVIG and/or corticosteroids did not affect the results. Children with AIT treated as fetuses had better long-term developmental-behavioral outcomes than their untreated siblings, perhaps because of higher in utero platelet counts. We speculate that platelets may possibly play a role in neurodevelopmental processes in the fetus.