Activated prothrombin complex concentrate-induced atypical hemolytic uremic syndrome treated with eculizumab

Abstract

Objective: Background: Case Report: Conclusions: Challenging differential diagnosis Atypical hemolytic uremic syndrome (aHUS) is a set of heterogenous disorders of thrombotic microangiopathy defined by thrombocytopenia, hemolytic anemia, and acute renal failure that is not mediated by shiga toxin. Factor Eight Inhibitor Bypassing Activity (FEIBA) is a concentrate of inactivated and activated coagulation factors that is approved for use to establish hemostasis in patients with hemophilia or acquired factor inhibitors. However, it has recently been used off-label as an anticoagulant reversal therapy among the general popula-tion. Additionally, post-market surveillance has shown increased thromboembolic adverse events, whereas mi-cro-thrombotic complications are rarely described. A 58-year-old man with a history of hypertension and a single deep vein thrombosis on warfarin presented with right upper-quadrant tenderness extending to the right flank. He was found to have a hepatic hematoma and was given activated prothrombin complex concentrate (aPCC) of 14 150 units of anti-inhibitor coagulant complex at 100 units per kilogram due to concern for active hemorrhage. Subsequently, he developed anemia, thrombocytopenia, and renal failure consistent with atypical HUS. He was treated with hemodialysis, cortico-steroids, plasma exchange, and 4 weekly doses of the anti-C5 antibody eculizumab. The patient subsequently recovered, demonstrating improved hemoglobin, creatinine, and platelets. He eventually achieved hemodi-alysis independence. Follow-up showed no evidence of recurrent atypical HUS and the patient has not needed maintenance eculizumab. Herein, we report the first case of aHUS associated with administration of a single large dose of aPCC for an-ticoagulation reversal. We postulate a potential mechanism for FEIBA-induced aHUS and report the efficacy of a short trial of eculizumab.