OBJECTIVES: Congenital thrombotic thrombocytopenic purpura (cTTP) (severe ADAMTS13 deficiency) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and diverse clinical signs and symptoms. Prophylactic plasma infusions are typically administered every 2-3 weeks to reduce the incidence of acute events and less severe manifestations. Need exists for a cTTP-specific patient-reported outcome (PRO) tool to assess patient burden and treatment outcomes, as existing tools do not adequately capture the range of cTTP symptoms and impacts. The objective is to develop a disease-specific instrument to measure salient symptoms and impacts of cTTP. METHODS: A conceptual model of cTTP symptoms and impacts was developed through an iterative process of literature review and interviews with hematologists (N=5) and patients (N=11). Items in the model were compared with currently available instruments, including HIT-6, MMSE, PHQ-8 and SF-36, and scales for analogous conditions, to assist in item generation. Two rounds of cognitive debriefing patient interviews (N=10) were conducted to revise the tool. RESULTS: Many of the salient symptoms and impacts in the conceptual model are not captured by comparator instruments. The newly-developed instrument contains 26 items measuring the intensity of patient-reported symptoms and impacts. It includes fatigue and pain types (11-point numerical scales) over the past 24 hours; bruising (numerical scale); symptoms of cognitive impairment, vision problems, and headache (Likert scales of frequency) over the past 7 days; impacts of symptoms (daily activities, depression, anger, irritability, frustration, anxiety, mood swings; Likert scales of frequency) over the past 7 days; and treatment experiences (numerical and Likert scales) over the past 2 weeks. CONCLUSIONS: This is the first PRO instrument developed to assess the salient symptoms and impacts of cTTP. Cognitive debriefing interviews conducted with patients confirmed the instrument is appropriate, comprehensive, and understandable. It provides information regarding burden of disease and may be useful in assessing outcomes of treatment.