Methylprednisolone Augments IV Immune Globulin Response in Children With ITP

Intravenous immune globulin (IVIG) plus intravenous methylprednisolone (IVMP) confers a more rapid increase in platelet counts in children with immune thrombocytopenia (ITP), compared with IVIG alone, according to a randomized study published in Blood Advances. Lead author Manuel Carcao, MD, of the University of Toronto, said that low platelet count is a risk factor for bleeding, including intracranial hemorrhage (ICH), even though the incidence of ICH in the pediatric ITP population is low.

The double-blind, placebo-controlled study enrolled children <18 years of age with a mean age of 9.4 years (range = 1.2-17.5 years) with acute or chronic ITP, platelet count of <20×109/L, and no evidence of life-threatening bleeding. Patients were randomized to either:

  • IV placebo made to look like IVMP administered over 1 hour (n=18)
  • IVMP 30 mg/kg administered over 1 hour (n=14)

Both treatments were immediately followed by IVIG 1 g/kg, which was administered over 2 to 3 hours. At baseline, the mean platelet count was 9.2×109/L. A total of 11 children had blood type O, and 23 patients had previously received IVIG. In addition, 26 children previously received corticosteroids prior to study entry; only 4 patients were treatment naïve. The mean overall Buchanan and Adix bleeding score at baseline was 1.32.

Adverse events (AEs) were reported in 30 patients. No severe bleeding episodes or unexpected severe AEs were reported. A lower proportion of patients in the combination therapy group experienced IVIG-related headaches during the 24- to 72-hour period. “This is important to know,” said Dr. Carcao, “as this approach can be instituted in patients who are prone to headache or in patients who have already reacted to IVIG with headache.”

For both groups, mean platelet counts rose to 14.6×109/L by the end of each treatment; 55% of all participants had a platelet count of ≥20×109/L by 8 hours after starting their assigned treatment, with no difference found between the groups at this early time point (p=0.99).

The mean platelet counts were significantly higher for children randomized to IVMP plus IVIG versus IVIG alone by 24 hours after treatment, however (77×109/L vs. 55×109/L, respectively; p=0.035). All patients treated with IVIG and IVMP achieved a platelet count of ≥20×109/L by 24 hours, while 89% of patients randomized to IVIG alone achieved a platelet count of ≥20×109/L at this time point (p=0.49). Around one-half of children randomized to IVIG alone and 77% of patients in the combined therapy group achieved a platelet count of ≥50×109/L.

“The finding that IVMP plus IVIG led to a higher platelet count at 24 hours compared with IVIG alone may suggest that even in patients with severe bleeding, this combination can raise platelet counts fairly rapidly,” said Dr. Carcao. He added that with this treatment plus platelet transfusions/tranexamic acid, there may be little need to undertake an emergency splenectomy.

At 72 hours, 1 week, and 21 days after treatment, the mean platelet counts for all children were 143×109/L, 161×109/L, and 40×109/L, respectively. No difference was found between the groups at each of these time points in terms of platelet counts, and there was no difference in response rates between males and females. Response rates also did not differ between children with acute versus chronic ITP, between patients who had received prior IVIG versus those who had not, or between children who had received prior steroids versus those who had not.

Limitations of this study include the small number of patients, unequal randomization, the exclusion of newly diagnosed children within 24 hours of presentation, the fact that only 4 patients were previously untreated, as well as the exclusion of children with life-threatening bleeding.

Despite these limitations, Dr. Carcao and colleagues suggest these results support the use of IVMP plus IVIG in children with ITP in situations when it is crucial to increase platelet counts, such as life-threatening bleeding. In these situations, however, the authors also advocate for administration of a large platelet transfusion and additional adjunctive hemostatic treatments, such as recombinant factor VIIa and IV tranexamic acid.


Carcao M, Silva M, David M, et al. IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP. Blood Adv. 2020;4:1492-1500.