Intravenous Immunoglobulin versus Careful Observation in Children with Newly Diagnosed Immune Thrombocytopenia: First Results of a Randomized Controlled Trial
Background and objectives:Management in children with newly diagnosed immune thrombocytopenia (ITP) consists of careful observation or treatment with corticosteroids or intravenous immunoglobulin (IVIg). In this multicenter randomized trial we studied efficacy and safety of careful observation versus intravenous immunoglobulin and tried to identify predictors of early recovery as well as predictors of response to IVIg.
Patients and methods: Children aged 3 months-16 years with newly diagnosed ITP, platelet counts ≤ 20 x 109/L and mild to moderate bleeding were included in 47 different hospitals. Within 72 hours after diagnosis patients were randomized to receive either a single infusion of 0.8 g/kg IVIg or careful observation and treatment only in case of severe bleeding. Clinical data were collected and laboratory studies were performed at diagnosis, after one week and after one month.
Results: At time of analysis, 172 patients were included, 88 males and 84 females, with a median age of 3.84 years (range 0-16 years). Median duration of symptoms prior to diagnosis was 3.00 days and median platelet count at diagnosis 6.00 x 109/L (range 0-20 x 109/L). Eighty-nine children (51.7%) experienced an infection and six children (3.5%) received a vaccination within four weeks prior to diagnosis of ITP. One-hundred-and-two children (59.3%) had skin bleeding only and 68 children (39.5%) had mucosal bleeding as well. Anti-glycoprotein antibodies were detected by indirect monoclonal antibody immobilization of platelet antibodies (MAIPA) in 16/154 children (10.4%). Eighty-six patients were randomized to receive IVIg, 86 to receive careful observation. No statistical significant differences regarding baseline characteristics were found between the IVIg and observation group, except for leukocyte count at diagnosis (observation group mean 8.40 x 109/L versus 9.34 x 109/L in IVIg group, p 0.048). After one week, overall response (platelet count ≥ 30 x 109/L and at least two-fold increase) to IVIg was seen in 77.9% (67/86), of whom 68.6% (59/86) showed complete response (platelet count ≥ 100 x 109/L). After one month, 80.2% (69/86) showed overall response and 61.6% (53/86) complete response. No predictors of complete response to IVIg after one week were found, regarding clinical parameters, blood cell counts, MAIPA results and thrombopoietin. In the observation group, overall response after one week was 38.4% (33/86) and complete response 20.9% (18/86). After one month, overall and complete response were 60.5% (52/86) and 39.5% (34/86), respectively. Children in the observation group with complete response after one week had a significantly shorter duration of symptoms prior to diagnosis than children without complete response (median 1.0 day vs 5.0 days, p<0.001) and more often a previous infection (77.8% vs 42.2%, p 0.008). After one month, only duration of symptoms was significantly different (p<0.001). Fourteen severe adverse events within the first month after inclusion were reported, 9 in the observation group and 5 in the IVIg group. All of these were transient.
Conclusion: Although response rate is higher in patients that received IVIg, careful observation is a safe alternative in children with newly diagnosed ITP with spontaneous complete recovery within 1 month in 39.5%. Children who recovered within 1 month had a significantly shorter duration of symptoms prior to diagnosis than children that did not. So far, no predictors of response to IVIg were found.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.