Key Points• Older age, insidious onset, no preceding infection, mild bleeding, and higher platelet count are the strongest risk factors for chronic ITP.• Intravenous immunoglobulin treatment seems to protect against development of chronic ITP.Childhood immune thrombocytopenia (ITP) is a rare autoimmune bleeding disorder. Most children recover within 6 to 12 months, but individual course is difficult to predict. We performed a systematic review and meta-analysis to identify predictors of chronic ITP. We found 1399 articles; after critical appraisal, 54 studies were included. The following predictors of chronic ITP in children, assessed in at least 3 studies, have been identified: female gender (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.04-1.31), older age at presentation (age ‡11 years; OR 2.47, 95% CI 1.94-3.15), no preceding infection or vaccination (OR 3.08,, insidious onset (OR 11.27,), higher platelet counts at presentation ( ‡20 3 10 9 /L: OR 2.15, 95% CI 1.63-2.83), presence of antinuclear antibodies (OR 2.87, 95% 1.57-5.24), and treatment with a combination of methylprednisolone and intravenous immunoglobulin (OR 2.67, 95% CI 1. 44-4.96). Children with mucosal bleeding at diagnosis or treatment with intravenous immunoglobulin alone developed chronic ITP less often (OR 0.39, 95% CI 0.28-0.54 and OR 0.71, 95% CI 0.52-0.97, respectively). The protective effect of intravenous immunoglobulin is remarkable and needs confirmation in prospective randomized trials as well as future laboratory studies to elucidate the mechanism of this effect. (Blood. 2014;124(22):3295-3307) IntroductionChildhood immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count ,100 3 10 9 /L) in the absence of other causes that may be associated with thrombocytopenia.1 Most children present with a typical history of acute development of purpura and bruising, often after a mild viral infection. Management of newly diagnosed ITP consists of careful observation, regardless of platelet count. Severe bleeding, occurring in only 3% to 5% of children, 2 requires treatment with corticosteroids, intravenous immunoglobulin (IVIg), or anti-Rhesus-D immunoglobulin, either alone or in combination and, if life threatening, also with platelet and red blood cell transfusions. 3,4 Chronic ITP is currently defined as thrombocytopenia ,100 3 10 9 /L lasting for .12 months.1 About 20% to 25% of children with newly diagnosed ITP will develop chronic disease. Because of the high impact of ITP on a child's everyday life and activities, as well as to decide whether treatment has to be instituted to influence the clinical course of ITP, it is of clinical significance if the course of the disease could be predicted at time of diagnosis.Several clinical, therapeutic, laboratory, and genetic predictors of chronic ITP have been evaluated in children.5-7 A systematic review or meta-analysis, however, has not yet been performed. In this study, we systematically analyzed all...

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• CRP enhances IgG-mediated respiratory burst and phagocytosis of platelets in vitro and their clearance in vivo.• CRP levels are increased in ITP patients and correlate with platelet counts and bleeding severity and predict time to recovery.Immune-mediated platelet destruction is most frequently caused by allo-or autoantibodies via Fcg receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo-and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients. (Blood. 2015;125(11): 1793-1802 IntroductionFetal or neonatal alloimmune thrombocytopenia (FNAIT) and immune thrombocytopenia (ITP) are both antibody-mediated disorders in which platelets are destroyed mainly through activating immunoglobulin (IgG) Fc receptors on phagocytes in the spleen and liver, eventually resulting in thrombocytopenia. 1 In childhood, ITP is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child, caused by development of platelet autoantibodies, with an incidence of ;5 in 100 000 children.2 Most children with newly diagnosed ITP will not suffer from serious bleeding and will recover within 12 months. In ;60% of ITP, there is a history of a prior infection. [1][2][3] FNAIT is a potentially destructive disease in pregnancies, with intracerebral hemorrhage (ICH) of the fetus or neonate as the most feared complication, resulting in perinatal death in 1% to 7% or in severe neurological impairments in 14% to 26% of affected pregnancies. [4][5][6][7] FNAIT is caused by maternal IgG platelet alloantibodies, in whites mainly directed against human platelet antigen (HPA)-1a (85%), that cross the placenta and destroy the platelets of the fetus or newborn. Immunization against HPA-1a occurs in ;1:450 random pregnancies. [8][9][10] Although platelet decrement is related to antibody titer in FNAIT, 8,11,12 this correlation is not strict, as cas...