Ipilimumab-Induced Granulomatous Disease Occurring Simultaneously With Disease Progression in a Patient With Metastatic Melanoma.

Malignant melanoma is the most aggressive cutaneous malignancy with dismal prognosis in the advanced setting. The food and drug administration approval of ipilimumab, the monoclonal antibody against cytotoxic T-lymphocyte antigen 4, has significantly changed treatment strategies for this disease. However, the spectrum of immune-related adverse events secondary to ipilimumab therapy is a growing area of research, and clinical observations of rare immune events as a result of such therapies continue to be reported since the approval. The co-occurrence of disease progression along with an immune-related adverse event is extremely rare. We here present the first case, to our knowledge, of diffuse nonnecrotizing granulomatous lymphadenopathy occurring simultaneously with disease progression in a patient with metastatic melanoma after receiving the second dose of ipilimumab.

Management of dabigatran-induced bleeding with continuous venovenous hemodialysis.

Dabigatran, a direct thrombin inhibitor, is increasingly used for stroke prevention in patients with non-valvular atrial fibrillation. Dabigatran has a stable pharmacokinetic profile with minimum drug interactions, and requires no routine laboratory evaluation to measure level of anticoagulation. This provides a huge advantage over warfarin, and has the potential to improve patient compliance. The disadvantages of dabigatran are the lack of a reversal agent to counter dabigatran-related bleeding and the absence of a widely available laboratory test that can quantify the extent of coagulopathy in dabigatran overdose. Hemodialysis can rapidly lower dabigatran levels and assist in controlling bleeding secondary to dabigatran overdose. However, in cases in which hemodynamic instability precludes the use of hemodialysis, alternative methods have to be utilized to control dabigatran-associated bleeding. Here we document a case of massive gastrointestinal bleeding secondary to dabigatran use that was successfully managed by continuous venovenous hemodialysis (CVVHD), along with supportive care with blood product transfusions. CVVHD reduces thrombin time and activated partial thrombin time, and causes a parallel decrease in amount of active bleeding. Finally, we show that compared to the rapid lowering of elevated thrombin time observed in hemodialysis, CVVHD requires several days to reduce thrombin time to normal range.