Girolami A, et al. - Given that hereditary prekallikrein (Fletcher factor) deficiency represents an uncommon entity defined by a prolonged activated partial thromboplastin time, and inhibitors of plasma kallikrein have recently been advocated for the prevention of hereditary angioedema and are under research for use in other indications, researchers tried to conservatively evaluate the influence of long-term inhibition of this pathway by examining reported comorbidities in patients with hereditary prekallikrein deficiency. They identified papers that documented data from patients with hereditary prekallikrein deficiency, explored in many medical literature databases. They analyzed data recording of cardiovascular, bleeding, and autoimmune-associated diseases. A total of 45 publications were analyzed. They found that 25 of 53 patients with prekallikrein deficiency were explicitly described as asymptomatic, with no comorbidities stated in another three cases. Post-surgery excessive bleeding episodes occurred in four patients. For three patients, autoimmune-associated diseases were documented. A connection between prekallikrein deficiency and comorbidities was not suggested by most of the reports.