Contribution of vascular abnormalities to gastrointestinal bleeding in patients with Glanzmann Thrombasthenia: mechanistic studies using endothelial colony forming cells (ECFCs)

Some congenital, hereditary disorders may provoke bleeding manifestations due to alterations in the number or function of blood platelets, small cell fragments circulating in blood and playing an essential role in the arrest of hemorrhage. One such condition is Glanzmann Thrombasthenia, a rare but serious bleeding disorder in which platelets do not exert their haemostatic function because they lack one essential receptor on their surface, glycoprotein GPIIb/IIIa (or α_IIbβ₃). We have recently described a patient with Glanzmann Thrombasthenia and gastrointestinal bleeding caused by gastrointestinal angiodysplasia, a digestive tract vascular malformation due to abnormal angiogenesis, which is the process of generation of blood vessels. Endothelial cells are the cells that line the internal side of blood vessels and they express a receptor, called α_vβ₃ which shares with platelet α_IIbβ₃the β₃subunit. Our hypothesis is that variants of β₃ causing Glanzmann Thrombasthenia may also cause gastrointestinal angiodysplasia leading to GI hemorrhages and we aim to unravel the molecular mechanisms involved in order to identify potential therapeutic targets of this potentially serious complication.
In this way, we will contribute to the knowledge of a rare genetic disease, disregarded by private and public funding, and possibly improve its treatment preventing gastrointestinal angiodysplasia.