Spontaneous bleeding in thrombocytopenia: Is it really spontaneous?

Spontaneous bleeding is a clinical hallmark of thrombocytopenia and can take multiple forms including petechiae, epistaxis, gum bleeding, or, in worst cases, intracranial hemorrhage. Those bleeding events are called " spontaneous " because they occur in the absence of overt trauma. Spontaneous bleeding manifestations have long been considered to be a direct consequence of low platelet counts. Nevertheless, although low platelet counts may lead to ultrastructural endothelial alterations, those alterations and the associated state of vascular fragility are unlikely sufficient to cause spontaneous rupture of the microvessel wall. Indeed, in addition to endothelial injury, factors capable of damaging the basement membrane are required to allow escape of red blood cells in the extravascular space. Therefore, despite their misleading name, spontaneous bleeding events in thrombocytopenia are most likely provoked and involve subclinical biological processes in which platelets normally intervene to ensure hemostasis. In this review, we discuss past and more recent studies on the possible triggers of spontaneous bleeding events in thrombocytopenia, with a particular focus on the role of inflammatory reactions.