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A four-factor prothrombin complex concentrate (4F-PCC) was recently licensed in the United States for urgent vitamin K antagonist (VKA) reversal based on two randomized clinical trials. These studies excluded patients at high risk of thrombosis; therefore, the risk of thrombotic complications in unselected patients remains a concern.This study retrospectively evaluated the incidence of thromboembolic events (TEEs) and death in patients who received 4F-PCC for VKA reversal. The study included 113 consecutive patients who were 18 years of age and older and were administered 4F-PCC for VKA reversal. The incidence of TEE and deaths was evaluated for up to 60 days after PCC administration or until the end of hospitalization, whichever came later.Seven (6.2%) patients developed TEEs and 17 (15%) patients died. PCC administration was probably related to TEE and subsequent death in two (1.8%) patients. Multivariate analysis revealed that a diagnosis of Factor V Leiden or antiphospholipid syndrome was predictive of TEE, and active malignancy was predictive of death.This study supports the safety of 4F-PCC for urgent VKA reversal even in unselected patients. The underlying type of hypercoagulable state and the dose of PCC may influence the incidence of TEE.

Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterized by a severe deficiency of ADAMTS13 activity. Although therapeutic plasma exchange (PLEX) is the standard of care, 30% to 50% patients develop exacerbation or relapse, requiring immunomodulatory agents. Of these agents, glucocorticoids, rituximab, and cyclosporine A are the most frequently used.We report a case of chronic relapsing TTP in a patient who had eight relapses over a 14-year period. After her seventh relapse, the patient demonstrated only partial response to glucocorticoids, two courses of rituximab, and cyclophosphamide. The eighth relapse occurred 58 days after her last PLEX and subsequent to this she received a course of bortezomib (Velcade, Millennium Pharmaceuticals, Inc.). After treatment with bortezomib the patient demonstrated a complete response with a progressive increase in ADAMTS13 activity from less than 5% to 22% accompanied by undetectable inhibitor, and she has remained PLEX free for more than 169 days.Bortezomib may serve as an adjunct treatment in patients with acquired TTP who exhibit an incomplete response or are refractory to conventional management.