Atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA), is a disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment. Gemcitabine, a commonly used chemotherapy, is emerging as a cause of aHUS. Although rare, the morbidity and mortality can be significant. Few studies have explored the use of eculizumab, an anti-C5 monoclonal antibody as a potential therapy for gemcitabine-induced aHUS.
A 45 year old Caucasian male with metastatic urothelial carcinoma was started on weekly gemcitabine (1000 mg/m2 per dose) to treat recurrent disease. During his seventh cycle, he was hospitalized for hypertension, acute kidney injury, and anemia. Laboratory data at that time revealed a hemoglobin of 6.2 g/dL (reference range 14.0-17.0 g/dL) and a platelet count of 70 x 109/L (reference range 140-400x 109/L). Hemolysis was suggested by an elevated lactate dehydrogenase (LDH) of 420 IU/L (reference range 125-240 IU/L), undetectable haptoglobin, and the presence of schistocytes on the peripheral smear (see Figure 1). Creatinine was elevated to 2.8 mg/dL (reference range 0.7-1.4 mg/dL) and an ADAMTS-13 (A disintegrin and metalloproteinase with a thromboSpondin type 1 motif, member 13) returned as normal. The patient was diagnosed with gemcitabineinduced aHUS. Gemcitabine was discontinued, and the patient was started on steroids. Two weeks later, he presented with generalized tonic-clonic seizures, uncontrolled hypertension, and worsening renal failure. His labs on admission showed continued hemolysis and thrombocytopenia. In light of the patient’s poor response to steroids, the decision was made to start eculizumab.
Karkowsky, MD, Raphael and Parikh, MD, Kinjal
"Eculizumab for Gemcitabine-Induced Hemolytic Uremic Syndrome: A Novel Therapy for an Emerging Condition,"
The Medicine Forum: Vol. 16
, Article 8.
Available at: https://jdc.jefferson.edu/tmf/vol16/iss1/8