In normal conditions, proplatelet-forming megakaryocytes release nascent platelet directly in the bloodstream (A). Thrombopoietic stimulating agents expand the megakaryocyte pool and increase platelet production and release (B). The MYH9^−/− mice replicate the megakaryocyte and platelet abnormalities observed in patients with MYH9-related diseases. The proplatelet formation occurs distant from vessels, with consequent platelet release inside the bone marrow environment. Only a few giant platelets are released in the bloodstream (C). When romiplostin is administered to these animals, the MYH9^−/− megakaryocyte pool expands, and it can be hypothesized that the release of giant platelets inside the bone marrow is boosted. As a result, several growth factors for fibroblasts are secreted from platelets into the environment (including transforming growth factor-β, basic fibroblast growth factor, and platelet-derived growth factor), inducing the progressive bone marrow fibrosis (D).