Retrospective Analysis of Clinical Response in Children with Severe Immune Thrombocytopenia Undergoing Treatment with Intravenous Immune Globulin

Background:

Childhood immune thrombocytopenia (ITP) is a common bleeding disorder characterized by an isolated thrombocytopenia resulting from unknown causes, commonly presenting between 1 to 10 years of age. Nearly one child in 20,000 will experience ITP each year in the United States. The American Society of Hematology recommends that children with platelet counts of <20,000/μL and significant mucous membrane bleeding, or with platelet counts of <10,000/μL and minor purpura, should receive treatment with intravenous immune globulin (IVIg), IV RhIG, or corticosteroids.

Objective:

The objectives of this retrospective analysis was to determine if pediatric patients with severe ITP are responding to IVIg treatment with or without concomitant corticosteroids and if different IVIg products have any difference in response. We evaluated mean platelet counts at initial presentation and following IVIg therapy. The endpoints of this study were rate, degree, and rapidity of the platelet count response, cost of treatment, adverse effects and comparison of these with different IVIg products.

Methods:

This study was a single center, retrospective analysis of patients undergoing IVIg treatment for severe ITP. After institutional IRB approval, subjects were identified through Intermountain's Enterprise Data Warehouse. Subjects were pediatric patients aged ≤18 years of age with immune thrombocytopenia that received treatment with IVIg from January 2009 through April 2015. Patients were eligible for inclusion if they had an initial platelet level of <20,000/mm³ drawn within 48 hours prior to starting IVIg therapy and at least one platelet level within seven days following IVIg administration. Patients were excluded if they received a platelet transfusion prior to IVIg therapy. Platelet increase was assessed by analyzing the mean difference in platelet increase between initial values preceding IVIg administration compared to the highest drawn platelet level within a 7 day period post-IVIg therapy. Three different IVIg products were used which included Gammagard, Gammagard S/D and Gamunex. Response was defined as a platelet rise to at least 20,000/mm³. Cost-effectiveness was also evaluated.

Results:

At Primary Children's Hospital between January 2009 and April 2015, approximately 150 patients were diagnosed with ITP, the majority of whom were either observed without treatment or received corticosteroid therapy. Forty six patients were identified as having severe ITP requiring IVIg therapy, of which 72% were males. Median age of ITP patients receiving IVIg was 8 years. Twelve patients were excluded, as eight patients received platelet transfusions, three patients had initial platelet levels above 20,000/mm³, and one patient did not have a documented follow-up platelet level. This left 34 eligible patients for data analysis. Twelve patients (35%) received both IVIg and steroids. Twenty two patients (65%) had an appropriate platelet response within the 7 day period. The mean platelet increase was 76,000/mm³ in patients who received IVIg. Mean platelet increase of 88,000/mm³ was observed in patients receiving only IVIg therapy, compared to 53,000/mm³ in patients receiving both IVIg and corticosteroids. Seventy-six percent of patients received Gammagard with an average platelet response of 88,000/mm³, of which 69% responded by day 7. Twelve percent of patients received Gamunex with an average platelet response of 89,000/mm³, of which 75% responded by day 7. Twelve percent of patients received Gammagard S/D with an average platelet response of 10,000/mm³, of which 25% responded by day 7. Average IVIg cost per patient was $2,736 with a mean expense of $36 per 1000/mm³ increase in platelet counts.

Conclusion: Similar to other published reports, patients with severe ITP responded well to IVIg therapy. Patients who failed to respond to initial steroid treatment experienced a platelet response with concomitant corticosteroid and IVIg therapy. Though the numbers are small, our study suggests for the first time that IVIg product with >98% IgG levels (i.e. Gammagard, Gamunex) have better response rates than Gammagard S/D which has 90% IgG level. Further analysis needs to be completed evaluating duration of therapeutic effect from IVIg. This information will be used to help detect a clinically meaningful response to IVIg therapy directed at increasing platelet counts and preventing ITP complications.