Activated Prothrombin Complex Concentrate-Induced Atypical Hemolytic Uremic Syndrome Treated with Eculizumab.

BACKGROUND 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 population. Additionally, post-market surveillance has shown increased thromboembolic adverse events, whereas micro-thrombotic complications are rarely described. CASE REPORT 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, corticosteroids, 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 hemodialysis independence. Follow-up showed no evidence of recurrent atypical HUS and the patient has not needed maintenance eculizumab. CONCLUSIONS Herein, we report the first case of aHUS associated with administration of a single large dose of aPCC for anticoagulation reversal. We postulate a potential mechanism for FEIBA-induced aHUS and report the efficacy of a short trial of eculizumab.

A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib.

Diffuse large B-cell lymphoma (DLBCL) is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC) type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton's agammaglobulinemia tyrosine kinase (BTK). This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB) DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient's demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.