Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure. Furthermore, a C5 inhibitor, eculizumab, has been successfully used in the treatment of GiTMA.
A 64-year-old Caucasian female with history of pancreatic adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of fluid overload and was found to have abnormal kidney function. Her BP was 195/110 mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 × 103/cmm, lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film. A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis for volume overload and daily plasmapheresis were initiated. After six days of plasmapheresis, renal function did not improve. Further work up revealed ADAMTS 13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative. Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal function failed to improve and eculizumab therapy was considered due to suspicion of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 × 109/L is highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26 mg/dl and platelet count of <30 × 109/L. She received intravenous eculizumab for eight months, which resulted in significant improvement of renal function. Other markers of hemolysis, namely LDH and bilirubin, also rapidly improved following eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two and eight weeks of initiation respectively.
Chemotherapy induced TMA is very rare and requires a high index of clinical suspicion for timely diagnosis. Discontinuation of the offending drug and supportive care is the main stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA. Further research is required to validate this approach.
Saif MW, McGee PJ. Hemolytic-uremic syndrome associated with gemcitabine: a case report and review of literature. JOP : Journal of the pancreas. 2005;6(4):369–74. PubMed
Tumma A. Atypical haemolytic uraemic syndrome associated with cabazitaxel in advanced prostate cancer. Medical Case Reports. 2016;2(3)
Kavanagh D, Goodship TH, Richards A: Atypical haemolytic uraemic syndrome. Br Med Bull 2006, 77-78:5–22.
Casper ES, Green MR, Kelsen DP, Heelan RT, Brown TD, Flombaum CD, Trochanowski B, Tarassoff PG, Phase II. Trial of gemcitabine (2,2′-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Investig New Drugs. 1994;12(1):29–34. CrossRef
Izzedine H, Isnard-Bagnis C, Launay-Vacher V, Mercadal L, Tostivint I, Rixe O, Brocheriou I, Bourry E, Karie S, Saeb S et al: Gemcitabine-induced thrombotic microangiopathy: a systematic review. In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. Volume 21, edn. England; 2006: 3038–3045.
Ruiz I, Del Valle J, Gomez A: Gemcitabine and haemolytic-uraemic syndrome. In: Annals of oncology : official journal of the European Society for Medical Oncology/ESMO. Volume 15, edn. England; 2004: 1575–1576.
van der Heijden M, Ackland SP, Deveridge S. Haemolytic uraemic syndrome associated with bleomycin, epirubicin and cisplatin chemotherapy--a case report and review of the literature. Acta oncologica (Stockholm, Sweden). 1998;37(1):107–9. CrossRef
Walter RB, Joerger M, Pestalozzi BC. Gemcitabine-associated hemolytic-uremic syndrome. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2002;40(4):E16. CrossRef
Kok VC, Wu SC, Lee CK. Successful remission of hemolytic-uremic syndrome during the third-line weekly gemcitabine for metastatic breast cancer. Breast cancer : basic and clinical research. 2014;8:57–9.
Asif A, Vachharajani T, Salman L, Nayer A. A Simplified Approach to the Diagnosis of Atypical HUS: Clinical Considerations and Practical Implications. The Open Urology & Nephrology Journal. 2014;9:91–4.
Weitz M, Amon O, Bassler D, Koenigsrainer A, Nadalin S. Prophylactic eculizumab prior to kidney transplantation for atypical hemolytic uremic syndrome. Pediatric nephrology (Berlin, Germany). 2011;26(8):1325–9. CrossRef
Starck M, Wendtner CM. Use of eculizumab in refractory gemcitabine-induced thrombotic microangiopathy. Br J Haematol. 2013;
Rogier T, Gerfaud-Valentin M, Pouteil-Noble C, Taleb A, Guillet M, Noel A, Broussolle C, Seve P. Clinical efficacy of eculizumab as treatment of gemcitabine-induced thrombotic microangiopathy: a case report. La Revue de Med Int. 2016;37(10):701–4. CrossRef
Turner JL, Reardon J, Bekaii-Saab T, Cataland SR, Arango MJ. Gemcitabine-associated thrombotic Microangiopathy: response to complement inhibition and Reinitiation of gemcitabine. Clin Colorectal Cancer. 2016;
Lopez Rubio ME, Rodado Martinez R, Illescas ML, Mateo Bosch E, Martinez Diaz M, de la Vara Inesta L, Cabezuelo B, Morales Albuja ME, Lucas Guillen E, Jimeno Garcia L: Gemcitabine-induced hemolytic-uremic syndrome treated with eculizumab or plasmapheresis: two case reports. Clinical nephrology 2017;87(2017)(2):100–106.
- The use of eculizumab in gemcitabine induced thrombotic microangiopathy
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