Research Article| Volume 224, P73-79, April 2023

Eculizumab in the management of drug-induced thrombotic microangiopathy: A scoping review of the literature

  • Aneeqa Zafar
    Division of Hematology, Bone Marrow Transplant and Cellular Therapy, Department of Internal Medicine, University of California, San Francisco, United States of America
    Search for articles by this author
  • Ming Yeong Lim
    Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah Health Sciences Center, United States of America
    Search for articles by this author
  • Mouhamed Yazan Abou-Ismail
    Corresponding author at: 30 N 1900 E, RM 1B390, Salt Lake City, UT 84112, United States of America.
    Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah Health Sciences Center, United States of America
    Search for articles by this author


      • Drug-induced thrombotic microangiopathy (DI-TMA) is a rare complication caused by various drugs.
      • DI-TMA is usually managed by drug discontinuation and supportive measures alone.
      • Studies on DI-TMA management are scarce, and whether complement-inhibition is effective is unknown.
      • In our scoping review, eculizumab was effective to achieve recovery in severe or refractory DITMA.


      Drug-induced TMA (DI-TMA) is a thrombotic microangiopathy (TMA) caused by certain drugs, usually managed by drug discontinuation and supportive measures. Data on the use of complement-inhibition with eculizumab in DI-TMA is scarce, and its benefit in cases of severe or refractory DI-TMA is unclear. We conducted a comprehensive search in PubMed, Embase and MEDLINE databases (2007–2021). We included articles that reported on DI-TMA patients treated with eculizumab and its clinical outcomes. All other causes of TMA were excluded. We evaluated the outcomes of hematologic recovery, renal recovery, and a composite of both (complete TMA recovery). 35 studies fulfilled our search criteria, which included 69 individual cases of DI-TMA treated with eculizumab. Most cases were secondary to chemotherapeutic agents, and the most implicated drugs were gemcitabine (42/69), carfilzomib (11/69), and bevacizumab (5/69). The median number of eculizumab doses given was 6 (range 1–16). 55/69 (80 %) patients achieved renal recovery, after 28–35 days (5–6 doses). 13/22 (59 %) patients were able to discontinue hemodialysis. 50/68 (74 %) patients achieved complete hematologic recovery after 7–14 days (1–2 doses). 41/68 (60 %) patients met criteria for complete TMA recovery. Eculizumab was safely tolerated in all cases, and appeared to be effective in achieving both hematologic and renal recovery in DI-TMA refractory to drug discontinuation and supportive measures, or with severe manifestations associated with significant morbidity or mortality. Our findings suggest that eculizumab may be considered as a potential treatment for severe or refractory DI-TMA that does not improve after initial management, although larger studies are needed.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Thrombosis Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Scully M.
        • Cataland S.
        • Coppo P.
        • de la Rubia J.
        • Friedman K.D.
        • Kremer Hovinga J.
        • et al.
        Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies.
        J. Thromb. Haemost. 2017; 15: 312-322
        • Abou-Ismail M.Y.
        • Kapoor S.
        • Citla Sridhar D.
        • Nayak L.
        • Ahuja S.
        Thrombotic microangiopathies: an illustrated review.
        Rese. Pract. Thromb. Haemostasis. 2022; 6e12708
        • George J.N.
        • Nester C.M.
        Syndromes of thrombotic microangiopathy.
        N. Engl. J. Med. 2014; 371: 654-666
        • George J.N.
        • Morton J.M.
        • Liles N.W.
        • Nester C.M.
        After the Party's over.
        N. Engl. J. Med. 2017; 376: 74-80
        • Saleem R.
        • Reese J.A.
        • George J.N.
        Drug-induced thrombotic microangiopathy: an updated systematic review, 2014–2018.
        Am. J. Hematol. 2018; 93: E241-E243
        • Yui J.C.
        • Van Keer J.
        • Weiss B.M.
        • Waxman A.J.
        • Palmer M.B.
        • D'Agati V.D.
        • et al.
        Proteasome inhibitor associated thrombotic microangiopathy.
        Am. J. Hematol. 2016; 91: E348-E352
        • Atallah-Yunes S.A.
        • Soe M.H.
        Drug-induced thrombotic microangiopathy due to cumulative toxicity of ixazomib.
        Case Reports in Hematology. 2018; 2018: 7063145
        • Al-Nouri Z.L.
        • Reese J.A.
        • Terrell D.R.
        • Vesely S.K.
        • George J.N.
        Drug-induced thrombotic microangiopathy: a systematic review of published reports.
        Blood. 2015; 125: 616-618
        • Joly B.S.
        • Coppo P.
        • Veyradier A.
        Thrombotic thrombocytopenic purpura.
        Blood. 2017; 129: 2836-2846
        • Dickey M.S.
        • Raina A.J.
        • Gilbar P.J.
        • Wisniowski B.L.
        • Collins J.T.
        • Karki B.
        • et al.
        Pembrolizumab-induced thrombotic thrombocytopenic purpura.
        J. Oncol. Pharm. Pract. 2020; 26: 1237-1240
        • Jacob S.
        • Dunn B.L.
        • Qureshi Z.P.
        • Bandarenko N.
        • Kwaan H.C.
        • Pandey D.K.
        • et al.
        Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the southern network on adverse reactions (SONAR).
        Semin. Thromb. Hemost. 2012; 38: 845-853
        • de Jorge E.G.
        • Macor P.
        • Paixão-Cavalcante D.
        • Rose K.L.
        • Tedesco F.
        • Cook H.T.
        • et al.
        The development of atypical hemolytic uremic syndrome depends on complement C5.
        J Am Soc Nephrol. 2011; 22: 137-145
        • Khosla J.
        • Yeh A.C.
        • Spitzer T.R.
        • Dey B.R.
        Hematopoietic stem cell transplant-associated thrombotic microangiopathy: current paradigm and novel therapies.
        Bone Marrow Transplant. 2018; 53: 129-137
        • Dvorak C.C.
        TA-TMA: state of the art for diagnosis and treatment.
        BloodAdvances. 2020; 4: 217
        • Mayer C.L.
        • Leibowitz C.S.
        • Kurosawa S.
        • Stearns-Kurosawa D.J.
        Shiga toxins and the pathophysiology of hemolytic uremic syndrome in humans and animals.
        Toxins (Basel). 2012; 4: 1261-1287
        • Fakhouri F.
        • Zuber J.
        • Frémeaux-Bacchi V.
        • Loirat C.
        Haemolytic uraemic syndrome.
        Lancet. 2017; 390: 681-696
        • Arksey H.
        • O'Malley L.
        Scoping studies: towards a methodological framework.
        Int. J. Soc. Res. Methodol. 2005; 8: 19-32
        • Fakhouri F.
        • Hourmant M.
        • Campistol J.M.
        • Cataland S.R.
        • Espinosa M.
        • Gaber A.O.
        • et al.
        Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm.
        Open-Label Trial. Am. J. Kidney Dis. 2016; 68: 84-93
        • Legendre C.M.
        • Licht C.
        • Muus P.
        • Greenbaum L.A.
        • Babu S.
        • Bedrosian C.
        • et al.
        Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.
        N. Engl. J. Med. 2013; 368: 2169-2181
        • Facchini L.
        • Lucchesi M.
        • Stival A.
        • Roperto R.M.
        • Melosi F.
        • Materassi M.
        • et al.
        Role of eculizumab in a pediatric refractory gemcitabine-induced thrombotic microangiopathy: a case report.
        J. Med. Case Rep. 2017; 11: 209