1.
IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP
Carcao M, Silva M, David M, Klaassen RJ, Steele M, Price V, Wakefield C, Kim L, Stephens D, Blanchette VS
Blood Advances. 2020;4(7):1492-1500
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Abstract
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 x 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 x 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 x 109/L (no group difference). By 24 hours, mean PCs were 76.9 x 109/L (B) vs 55 x 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.
PICO Summary
Population
Children with immune thrombocytopenia (n=32).
Intervention
IV methylprednisolone (IVMP 30 mg/kg) followed by IVIG (Gamunex 10%) 1 g/kg, (n=14).
Comparison
IV placebo followed by IVIG (Gamunex 10%) 1 g/kg, (n=18).
Outcome
By 8 hours after initiating therapy, 55% of all children had a platelet count (PC) >/=20 x 109/L (no group difference). By 24 hours, mean PCs were 76.9 x 109/L (B) vs 55 x 109/L (A). No patient experienced severe bleeding/unexpected severe associated adverse events. There were statistically fewer IVIG-related headaches in the group receiving combination therapy.
2.
Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production
Semple JW, Allen D, Rutherford M, Woloski M, David M, Wakefield C, Butchart S, Freedman J, Blanchette V, Canadian Children's Platelet Study Group
American Journal of Hematology. 2002;69((3):):225-7.
Abstract
Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity.