Immune thrombocytopenia (ITP) is an autoimmune disease with an incidence ranging from 3 to 5 per 100,000 individuals. In the pediatric age group, ITP is mostly acute self-limiting and induced by viral infections, while in adults the disorder is usually chronic. The disease could be asymptomatic or manifested by easy bruising, bleeding tendency, or blood extravasation from capillaries into the mucous membranes and skin [1, 2].

ITP pathogenesis involves both increased peripheral platelet destruction and suppression of the platelet production [1]. Increased platelets destruction is attributed to immunoglobulin G autoantibodies against platelet membrane glycoproteins. Abnormal T-cells activity represents the stimulus for the autoantibody production [3]. Coating of platelets with IgG renders them more prone to opsonization and phagocytosis by the reticuloendothelial system [4].

Apoptosis is considered the main pathophysiological process that controls the cell life span and removal of the infected or damaged nucleated cells. Although platelets are anucleate cells, they undergo events similar to apoptosis [5, 6]. There are two main apoptotic pathways that could regulate the programmed platelet death: the mitochondrial or intrinsic pathway and the death receptor or extrinsic pathway [7]. The latter is initiated by the ligation of death receptors, belonging to the tumor necrosis factor receptor superfamily, that activate the initiator caspase (procaspase 8) with subsequent activation of the effector caspases by caspase 8, such as caspase 3, 6 and 7 [8]. While the intrinsic apoptosis pathway is regulated by members of the B-cell lymphoma protein 2 family (BCL2), which contain both pro-survival and pro-death proteins that could induce changes in the mitochondrial outer membrane with subsequent efflux of the cytochrome c and other apoptogenic proteins into the cytoplasm. Once released, cytochrome c assembles with the initiator caspase (procaspase 9) and apoptotic protease-activating factor 1 to form the apoptosome, which activates caspase 9 and downstream effector caspases [8].

Murine ITP studies have shown that antiplatelet antibodies could induce apoptotic-like processes, and that the intravenous immunoglobulin (IVIG) treatment could decrease these events [9, 10]. Concerning human ITP, platelet apoptosis was suggested in children with newly diagnosed ITP in the form of activated caspase 3, 8 and 9, which were suppressed by the IVIG infusion [11]. Moreover, another study revealed that platelets from adult patients with chronic ITP expressed higher phosphatidylserine exposure associated with dysfunction of the dendritic cells, although other platelet apoptosis markers could not be demonstrated in this study [12]. A more recent study concerning adults with ITP also confirmed the relevance of platelet apoptosis in ITP [13].

The initial lines of ITP treatment include steroids to suppress the immune system and limit platelets destruction. The dose and mode of administration are determined by the platelet count and presence of active bleeding [14]. IVIG is another drug of choice as it leads to increased platelet counts, besides blockage of the reticuloendothelial system via Fc-receptors and it interferes with the apoptotic processes in platelets [14,15,16,17].

To our knowledge, few studies were conducted about apoptosis markers of newly diagnosed ITP in the pediatric age group in humans [11, 18]. Most of the previous studies, concerning apoptosis in ITP, were conducted in animal models or human adults [9, 10, 12, 13].

We conducted our preliminary study to investigate the possible role of the apoptotic markers (caspase 3, caspase 8 and BCL2) in the pathogenesis and course of newly diagnosed ITP, being markers for both apoptosis pathways (caspase 3 and caspase 8 for the extrinsic pathway while BCL2 for the intrinsic pathway). We also evaluated the effects of the treatment on the apoptotic markers of the newly diagnosed ITP children.