Collaboration between health care professionals and the pharmaceutical industry often drives medical progress and, thus, benefits patients. Clinical trials reflect this reality, as industry sources support about half of the investigations focused on drugs or devices, raising concerns about potential conflicts of interest (COIs).¹ Systematic reviews suggest an apparent bias of published studies that were more likely to report positive findings when the authors received support from industry.^2,3 While journal editors responded to these findings by mandating disclosures of potential COIs,^4-6 the possible extent of industry sponsorship came to light in the course of investigations by the Department of Justice, which led to a settlement between the United States and 5 companies owing to concerns about violations of federal anti-kickback regulations, as physicians had received consulting fees for using joint implants produced by these companies.⁷

Hereditary thrombotic thrombocytopenic purpura (hTTP), also known as Upshaw–Schulman syndrome, is a rare genetic disorder caused by mutations in the ADAMTS13 gene that leads to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. The result is circulating ultra-large multimers of VWF that can cause microthrombi, intravascular occlusion and organ damage, especially at times of turbulent circulation. Patients with hTTP may have many overt or clinically silent manifestations, and a high index of suspicion is required for diagnosis. For the treatment of hTTP, the goal is simply replacement of ADAMTS13. The primary treatment is prophylaxis with plasma infusions or plasma-derived factor VIII products, providing sufficient ADAMTS13 to prevent acute episodes. When acute episodes occur, prophylaxis is intensified. Recombinant ADAMTS13, which is near to approval, will immediately be the most effective and also the most convenient treatment. In this review, we discuss the possible clinical manifestations of this rare disease and the relevant differential diagnoses in different age groups. An extensive discussion on prophylaxis and treatment strategies is also presented. Unique real patient cases have been added to highlight critical aspects of hTTP manifestations, diagnosis and treatment.

Persons with hemophilia A are at risk of inhibitor development with repeated exposures to factor (F)VIII concentrates. When persons with nonsevere hemophilia A (NSHA) develop inhibitors, they are at risk of developing severe bleeding manifestations like persons with severe hemophilia A (SHA). Evidence to guide inhibitor eradication in this population is limited as opposed to persons with SHA who develop inhibitors. Hence, inhibitor eradication strategies in NSHA are based on observational and retrospective data and are largely adopted from evidence derived from SHA with inhibitors. Can immune tolerance induction be used for patients with NSHA who develop inhibitors? In this case series, we describe our single institutional experience with the management of 5 persons with NSHA who developed FVIII inhibitors, leading to significant bleeding complications, and underwent successful immune tolerance induction with eradication of FVIII inhibitor. More research specific to persons with NSHA with inhibitors is warranted to develop guidelines regarding indications and strategies for inhibitor eradication therapy.