Immune-mediated thrombotic thrombocytopenic purpura (iTTP) results from autoantibody-mediated severe deficiency of ADAMTS13, the Von Willebrand factor (VWF)-cleaving protease. In this context, ultra-large VWF multimers accumulate in the circulation, leading to increased platelet clumping, with subsequent severe thrombocytopenia, microangiopathic hemolytic anemia and multiorgan failure. The anti-VWF nanobody caplacizumab is licensed for adults with iTTP. Prospective controlled trials and national real-world studies have provided evidence that caplacizumab improved outcome of the acute phase of the disease. However, whether caplacizumab decreases mortality, and the optimal timing of caplacizumab initiation, remain to be determined. To address these questions, an international survey, the Capla 500+ project, has been conducted.