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Ciclosporin/epoetin-alfa/prednisone Various toxicities: 2 case reports

In a case series, a 75-year-old-woman and a 66-year-old-man were described of whom, the woman developed pure red cell aplasia and anti-erythropoietin antibody positive during treatment with epoetin-alfa; additionally, she developed oesophageal candidiasis and hand tremors during treatment with ciclosporin and prednisone. The man developed pure red cell aplasia and antierythropoietin antibody positive during treatment with epoetin-alfa for anaemia [not all routes and outcomes stated]. Case 1: The woman with a history of chronic kidney disease secondary to hypertensive nephrosclerosis was managed conservatively for nearly 2 years. Two months before initiation of renal replacement therapy in January 2015, she started treatment with SC epoetin alfa [initial dose not stated] and at that time, her haemoglobin (Hb) level was below 10 g/dL. In March 2015, at the start of haemodialysis, she was anaemic and her Hb was 8.5 g/dL with absolute iron deficiency. She then started IV iron hydroxide and the dose of SC epoetin alfa was increased to 12,000IU weekly. In May 2015, her haemoglobin improved and it was 12 g/dL and iron stores were also found to be normalised. Between July 2015 and October 2015, while on epoetin alfa therapy, her Hb dropped significantly to below 8 g/dL despite changes in dosage of epoetin alfa. Because of symptomatic anaemia, blood transfusions were required and thus she was hospitalised to investigate the causes of anaemia unresponsive to epoetin alfa. She underwent upper gastrointestinal (UGI) endoscopy and colonoscopy in 2nd semester of 2015 and in 1st semester of 2016, which revealed no GI bleeding. Her reticulocyte count was low and direct and indirect Coombs tests were negative for haemolysis. Despite treatment with epoetin alfa in doses 12,000IU per week, she had persistent asthenia and weakness associated with low haemoglobin levels and required monthly blood transfusions. In June 2016, blood testing and bone marrow examination with myelography revealed erythroid hypoplasia. The analysis suggested that she had pure red cell aplasia (PRCA) associated with anti-erythropoietin antibodies. In Aug 2016, she tested positive for anti-erythropoietin antibodies and therapy with epoetin alfa was discontinued. She then received immunosuppressant therapy with prednisone 1 mg/kg per day with further de-escalation and ciclosporin [cyclosporin] 4 mg/kg per day, divided in two doses. Her Hb levels improved gradually after the introduction of immunosuppressant therapy. In between September 2016 and October 2016, her Hb was 9.2 g/dL, and since then she was not offered packed red blood cells. Immunosuppressant therapy with ciclosporin and prednisone was discontinued after four months because of side effects including oesophageal candidiasis and persistent hand tremors. Nevertheless, her haemoglobin levels were stable and she was off epoetin alfa. Case 2: The man (JWSA) had advanced chronic kidney disease secondary to adult polycystic kidney