Neurologic complications of treatment of childhood acute immune thrombocytopenic purpura with intravenously administered immunoglobulin G

doi:10.1016/S0022-3476(97)70355-X

The Journal of Pediatrics

Volume 130, Issue 2, February 1997, Pages 281-283

https://doi.org/10.1016/S0022-3476(97)70355-X Get rights and content

Abstract

We studied the incidence, associated morbidity, and impact on health care charges of neurologic complications in 38 children with acute immune thrombocytopenic purpura (ITP) treated with intravenously administered IgG. Thirteen patients (34%) had transient neurologic complications, manifested by severe headache, nausea, and, rarely, aseptic meningitis. Computed tomography was performed in nine patients. Twelve patients were hospitalized longer than was required for their ITP alone. Neurologic complications caused by the IgG preparations used in the treatment of childhood ITP occur more frequently than has previously been suggested and may substantially increase the cost of treatment. (J Pediatr 1997;130;281-3)

Section snippets

METHODS

We reviewed the records of all children with acute ITP treated at the Children's Hospital of Philadelphia from July 1993 through December 1995. The diagnosis of ITP was established by clinical findings, platelet counts less than 20 × 10 ⁹ /L, and normal or increased numbers of megakaryocytes in the bone marrow. Data from patients who were treated with IVIgG were analyzed further. IVIgG was infused intravenously according to manufacturers' recommendations. The rate of the infusion never exceeded

RESULTS

Acute ITP was diagnosed in 75 children from July 1993 through December 1995. Thirty-eight children were treated with IVIgG. Thirty-six had a new onset of ITP, and two had a relapse of ITP after more than 3 years of normal platelet counts. The mean age of the patients was 5 years (range, 8 months to 19 years), and 21 were boys. The mean platelet count at presentation was 7 × 10 ⁹ /L (range, 2 to 17 × 10 ⁹ /L). Seventeen patients received Sandoglobulin, 16 received Venoglobulin, and three

DISCUSSION

Neurologic complications from IVIgG therapy include fever, headache, nausea, meningismus and photophobia, which may all be part of a continuum of disease caused by meningeal inflammation of variable severity. ³ Aseptic meningitis is the most severe form of this disease, and at least 36 cases of aseptic meningitis after IVIgG therapy have been reported. ⁴ In the only reported prospective study, mild to moderate headache and severe headache with aseptic meningitis occurred in 56% and 11%,

References (5)

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A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura
J Pediatr
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DS. Beardsley
Platelet abnormalities in infancy and childhood

There are more references available in the full text version of this article.

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Citation Excerpt :
Furthermore its use is associated with a considerable incidence of early (fever and chills) and/or delayed (1-3 days) complications (aseptic meningitis, headache, nausea, and vomiting).22,23 These complications, which are more common with larger/repeated doses, can result in additional morbidity/health care costs due to prolonged hospitalizations, hospital readmissions, emergency room visits, and neuroimaging costs.22,24 Many investigators have reported that in ITP, IVIG has a quicker onset of action than corticosteroids, leading to a faster increment in PC.15,25
Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 10⁹/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 10⁹/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 10⁹/L (no group difference). By 24 hours, mean PCs were 76.9 × 10⁹/L (B) vs 55 × 10⁹/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.
Primary Immune Thrombocytopenia
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Information for healthcare providers on general features of IGIV with emphasis on differences between commercially available products
2010, Autoimmunity Reviews
Intravenous immunoglobulin (IGIV) has provided an essential replacement therapy for primary and secondary immunodeficiencies patients and prophylaxis of infectious diseases in them. It is also used in several autoimmune and chronic inflammatory disorders. An overview of IGIV with information on several commercially available IGIV products is discussed.
Medline databases and literature provided by the manufacturer for each product presented in the manuscript.
From the vast body of information on IGIV, only those studies were selected that were pertinent to general features of IGIV (as presented below) or information provided by the manufacturer that facilitated comparing one product to the other.
Data was extracted on production, and purification procedures, removal of infectious agents, physical and biochemical properties and issues of safety. Data was extracted only for products available in the US.
IGIV is prepared using pooled plasma. The purification of IGIV is a complex and multi-step process. There is a reciprocal relationship between the purity of IgG in the product and the recovery rate from the total plasma. It is quite possible that some of the biological mediators of the inflammatory and immune systems may be present in trace amounts. Screening and removal of blood borne pathogens is necessary and there are several different techniques available. The specifics of the administration are often variable and no consistent pattern or protocol has been used. When limited dosages are required IGIV may be administered subcutaneously. The side effects associated with IGIV are usually mild and self-limiting.
There are differences in products produced by different manufacturers. The current data does not provide sufficient detail or information to be able to make specific recommendations for the use of a given commercial preparation in a specific disease state. The use of IGIV is associated with certain common and uncommon side effects. The identification of risk factors that might predispose a patient to developing them have been studied and reported. In choosing a IGIV preparation the user may avoid features that may predispose to certain side effects. Equally important is monitoring of patients during and after the IGIV therapy.
Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura
2008, Blood
Citation Excerpt :
Recently a 26-item health-related quality-of-life questionnaire was validated in pediatric patients with both acute and chronic ITP to assess disease burden of ITP on children and their families.7 The side effects of medications include weight gain, moodiness, and hyperglycemia related to steroid use, in addition to adverse effects, such as headache and aseptic meningitis associated with IVIG11 and intravascular hemolysis after anti-D immunoglobulin administration.12,13 Lastly, systematic cost analysis methods have been applied to evaluate different treatment modalities.10
Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm³ and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes.
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^☆: From the Division of Hematology, Children's Hospital of Philadelphia, and the Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia.

^☆☆: Reprint requests: Alan R. Cohen, MD Division of Hematology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104.

^★: 0022-3476/97/$5.00 + 0 9/21/77302

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Neurologic complications of treatment of childhood acute immune thrombocytopenic purpura with intravenously administered immunoglobulin G☆,☆☆,★

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

J Pediatr

Platelet abnormalities in infancy and childhood