A 56 year-old-man with a history of stage IV metastatic pancreatic cancer on gemcitabine/ abraxane for treatment with last dose occurring 8 days prior to admission presented with persistent fatigue. On admission, he denied diarrhea, confusion, headaches, or fevers. He further denied sick contacts or recent travel. He did not consume any quinine or tonic water. Admission labs were notable for hemoglobin of 4.8 g/dL and platelets of 34000/microliter. Serum studies showed a BUN of 79mg/dL and creatinine of 3.9mg/dL. His LDH was 925units/L. Peripheral smear revealed schistocytes. ADAMTS13 level was low (37%). C3, C4 levels were low (76 and 6 respectively). Given the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, the patient was diagnosed with Hemolytic Uremic Syndrome. He started plasmapheresis and after eight daily sessions, his platelet count and LDH improved. However, his renal function continued to worsen and hemodialysis was initiated. His platelets and LDH drifted into the abnormal range following plasmapheresis, and he began eculizumab therapy. His platelet count improved slowly. LDH stabilized, and he no longer required plasmapheresis. The patient had a prolonged hospital course and went home on hemodialysis and weekly eculizumab infusions.
HUS is primarily a disease of infancy and early childhood, but can occur in adults and is often associated with a poorer prognosis. It is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. 90% of HUS cases are linked to infections like shiga-toxin producing E.coli and streptococcus pneumoniae, mostly resolving without sequelae. Remaining 10% are atypical HUS caused by aberrant complement activation due to genetic or sporadic mutations of complement and regulatory pathways causing direct cell lysis and kidney damage. Atypical HUS is associated with high mortality. In this case, the inciting event is likely the patient’s recent treatment with gemcitabine. The pathophysiology of gemcitabine induced HUS is not well understood. It is thought that gemcitabine directly damages endothelial cells, causing platelet aggregation and intravascular hemolysis. Initial treatment of atypical HUS is plasmapheresis. Newer treatment modalities include monoclonal antibodies, specifically eculizumab (Soliris). It is a complement activation inhibitor that targets the uncontrolled complement activation arresting the platelet activation and systemic TMA. The adverse effects of these drugs can be life-threatening infections with encapsulated organisms. Careful discussion and education with the patient and family needs to occur prior to initiation of treatment.
Goals of care were addressed extensively and the patient had the opportunity to weigh the risks and benefits of treatment during the hospitalization. After much thought, he wanted to continue with the eculizumab in order to have more time with his family.
To cite this abstract:Mustafa SO. Hus-A Common Presentation of a Rare Disease. Abstract published at Hospital Medicine 2016, March 6-9, San Diego, Calif. Abstract 704. Journal of Hospital Medicine. 2016; 11 (suppl 1). https://www.shmabstracts.com/abstract/hus-a-common-presentation-of-a-rare-disease/. Accessed May 22, 2019.