In summary, the herein described Cdc42/RhoA regulatory circuit downstream of GPIb ensures a tight control of transendothelial platelet biogenesis in the BM and opens new avenues to treat both inherited and acquired forms of thrombocytopenia that are major causes of bleeding in man, and additionally to modulate in vitro production of platelets in the field of transfusion medicine. Here, RHOA is linked to Thrombocytopenia.