Key Points In children with newly diagnosed ITP, IVIg treatment at diagnosis does not result in a lower rate of chronic ITP. Upfront treatment with IVIg led to faster recovery and less severe bleeding events.

Key Points• Pediatric chronic ITP patients with a severe bleeding phenotype exhibit functional platelet defects.• The platelet microaggregation test and the platelet reactivity assay are able to assess platelet function at extremely low platelet count.Immune thrombocytopenia (ITP) is an autoimmune disease with a complex heterogeneous pathogenesis and a bleeding phenotype that is not necessarily correlated to platelet count. In this study, the platelet function was assessed in a well-defined cohort of 33 pediatric chronic ITP patients. Because regular platelet function test cannot be performed in patients with low platelet counts, 2 new assays were developed to determine platelet function: first, the microaggregation test, measuring in platelets isolated from 10 mL of whole blood the platelet potential to form microaggregates in response to an agonist; second, the platelet reactivity assay, measuring platelet reactivity to adenosine diphosphate (ADP), convulxin (CVX), and thrombin receptor activator peptide in only 150 mL of unprocessed whole blood. Patients with a severe bleeding phenotype demonstrated a decreased aggregation potential upon phorbol myristate acetate stimulation, decreased platelet degranulation following ADP stimulation, and a higher concentration of ADP and CVX needed to activate the glycoprotein IIbIIIa complex compared with patients with a mild bleeding phenotype. In conclusion, here we have established 2 functional tests that allow for evaluation of platelet function in patients with extremely low platelet counts ( <10 9 ). These tests show that platelet function is related to bleeding phenotype in chronic ITP. (Blood. 2014;123(10):1556-1563