Drug-Associated Thrombotic Microangiopathies

Abstract

Thrombotic microangiopathy is a pathological process that results in thrombocytopenia, schistocytes, and organ ischemia. A wide variety of causes of thrombotic microangiopathy have been described, each associated with a different pathological stimulus and predisposition toward certain vascular territories. This review will summarize our understanding of key drugs that have been classically and newly associated with thrombotic microangiopathy as well as mention of treatment options focusing on the role of plasma exchange.

Keywords

drug - thrombotic microangiopathy - plasma exchange

• References

• 1 Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347 (8) 589-600
• 2 Copelovitch L, Kaplan BS. The thrombotic microangiopathies. Pediatr Nephrol 2008; 23 (10) 1761-1767
• 3 Szczepiorkowski ZM, Winters JL, Bandarenko N , et al. Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher 2010; 25 (3) 83-177
• 4 Bennett CL, Davidson CJ, Raisch DW, Weinberg PD, Bennett RH, Feldman MD. Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention. Arch Intern Med 1999; 159 (21) 2524-2528
• 5 Bennett CL, Kiss JE, Weinberg PD , et al. Thrombotic thrombocytopenic purpura after stenting and ticlopidine. Lancet 1998; 352 (9133) 1036-1037
• 6 Steinhubl SR, Tan WA, Foody JM, Topol EJ. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT investigators. Evaluation of platelet IIb/IIIa inhibitor for stenting. JAMA 1999; 281 (9) 806-810
• 7 Zakarija A, Kwaan HC, Moake JL , et al. Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008). Kidney Int Suppl 2009; (112) S20-S24
• 8 Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Yarnold PR, Kwaan HC, Green D. Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60 cases. Ann Intern Med 1998; 128 (7) 541-544
• 9 Tsai HM, Rice L, Sarode R, Chow TW, Moake JL. Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated thrombotic thrombocytopenic purpura. Ann Intern Med 2000; 132 (10) 794-799
• 10 Mauro M, Zlatopolskiy A, Raife TJ, Laurence J. Thienopyridine-linked thrombotic microangiopathy: association with endothelial cell apoptosis and activation of MAP kinase signalling cascades. Br J Haematol 2004; 124 (2) 200-210
• 11 Symeonidis A, Kouraklis-Symeonidis A, Seimeni U , et al. Ticlopidine-induced aplastic anemia: two new case reports, review, and meta-analysis of 55 additional cases. Am J Hematol 2002; 71 (1) 24-32
• 12 Bennett CL, Connors JM, Carwile JM , et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000; 342 (24) 1773-1777
• 13 Bennett CL, Kim B, Zakarija A , et al. Two mechanistic pathways for thienopyridine-associated thrombotic thrombocytopenic purpura: a report from the SERF-TTP Research Group and the RADAR Project. J Am Coll Cardiol 2007; 50 (12) 1138-1143
• 14 Qureshi ZP, Armstrong J, Bennett CL. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic purpura: a twenty year review. Blood 2011; 118 (21) 969
• 15 Zarifian A, Meleg-Smith S, O'donovan R, Tesi RJ, Batuman V. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int 1999; 55 (6) 2457-2466
• 16 Van Buren D, Van Buren CT, Flechner SM, Maddox AM, Verani R, Kahan BD. De novo hemolytic uremic syndrome in renal transplant recipients immunosuppressed with cyclosporine. Surgery 1985; 98 (1) 54-62
• 17 Young BA, Marsh CL, Alpers CE, Davis CL. Cyclosporine-associated thrombotic microangiopathy/hemolytic uremic syndrome following kidney and kidney-pancreas transplantation. Am J Kidney Dis 1996; 28 (4) 561-571
• 18 Trimarchi HM, Truong LD, Brennan S, Gonzalez JM, Suki WN. FK506-associated thrombotic microangiopathy: report of two cases and review of the literature. Transplantation 1999; 67 (4) 539-544
• 19 Elliott MA, Nichols Jr WL, Plumhoff EA , et al. Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review. Mayo Clinic Proceedings 2003; 78 (4) 421-430
• 20 Perico N, Zoja C, Benigni A, Ghilardi F, Gualandris L, Remuzzi G. Effect of short-term cyclosporine administration in rats on renin-angiotensin and thromboxane A2: possible relevance to the reduction in glomerular filtration rate. J Pharmacol Exp Ther 1986; 239 (1) 229-235
• 21 McCauley J, Bronsther O, Fung J, Todo S, Starzl TE. Treatment of cyclosporin-induced haemolytic uraemic syndrome with FK506. Lancet 1989; 2 (8678–8679) 1516
• 22 Myers JN, Shabshab SF, Burton NA, Nathan SD. Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome. J Heart Lung Transplant 1999; 18 (10) 1024-1026
• 23 Wiener Y, Nakhleh RE, Lee MW , et al. Prognostic factors and early resumption of cyclosporin A in renal allograft recipients with thrombotic microangiopathy and hemolytic uremic syndrome. Clin Transplant 1997; 11 (3) 157-162
• 24 Zent R, Katz A, Quaggin S , et al. Thrombotic microangiopathy in renal transplant recipients treated with cyclosporin A. Clin Nephrol 1997; 47 (3) 181-186
• 25 Fung MC, Storniolo AM, Nguyen B, Arning M, Brookfield W, Vigil J. A review of hemolytic uremic syndrome in patients treated with gemcitabine therapy. Cancer 1999; 85 (9) 2023-2032
• 26 Humphreys BD, Sharman JP, Henderson JM , et al. Gemcitabine-associated thrombotic microangiopathy. Cancer 2004; 100 (12) 2664-2670
• 27 Gore EM, Jones BS, Marques MB. Is therapeutic plasma exchange indicated for patients with gemcitabine-induced hemolytic uremic syndrome?. J Clin Apher 2009; 24 (5) 209-214
• 28 Glezerman I, Kris MG, Miller V, Seshan S, Flombaum CD. Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution. Clin Nephrol 2009; 71 (2) 130-139
• 29 Lesesne JB, Rothschild N, Erickson B , et al. Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry. J Clin Oncol 1989; 7 (6) 781-789
• 30 Proia AD, Harden EA, Silberman HR. Mitomycin-induced hemolytic-uremic syndrome. Arch Pathol Lab Med 1984; 108 (12) 959-962
• 31 Bradner WT. Mitomycin C: a clinical update. Cancer Treat Rev 2001; 27 (1) 35-50
• 32 Cattell V. Mitomycin-induced hemolytic uremic kidney. An experimental model in the rat. Am J Pathol 1985; 121 (1) 88-95
• 33 Nagaya S, Wada H, Oka K , et al. Hemostatic abnormalities and increased vascular endothelial cell markers in patients with red cell fragmentation syndrome induced by mitomycin C. Am J Hematol 1995; 50 (4) 237-243
• 34 Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 2004; 103 (11) 4043-4049
• 35 McLeod BC. Apheresis: Principles and Practice. 3rd ed. Bethesda, MD: AABB Press; 2010
• 36 Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 2004; 65 (6) 2003-2017
• 37 Eremina V, Jefferson JA, Kowalewska J , et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358 (11) 1129-1136
• 38 Kapiteijn E, Brand A, Kroep J, Gelderblom H. Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukoencephalopathy syndrome. Ann Oncol 2007; 18 (10) 1745-1747
• 39 Izzedine H, Brocheriou I, Deray G, Rixe O. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant 2007; 22 (5) 1481-1482
• 40 Bollée G, Patey N, Cazajous G , et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant 2009; 24 (2) 682-685
• 41 Sugimoto H, Hamano Y, Charytan D , et al. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem 2003; 278 (15) 12605-12608
• 42 Scappaticci FA, Skillings JR, Holden SN , et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007; 99 (16) 1232-1239
• 43 Zhu X, Wu S, Dahut WL, Parikh CR. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis 2007; 49 (2) 186-193
• 44 Frangié C, Lefaucheur C, Medioni J, Jacquot C, Hill GS, Nochy D. Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol 2007; 8 (2) 177-178
• 45 van Heeckeren WJ, Ortiz J, Cooney MM, Remick SC. Hypertension, proteinuria, and antagonism of vascular endothelial growth factor signaling: clinical toxicity, therapeutic target, or novel biomarker?. J Clin Oncol 2007; 25 (21) 2993-2995
• 46 Roncone D, Satoskar A, Nadasdy T, Monk JP, Rovin BH. Proteinuria in a patient receiving anti-VEGF therapy for metastatic renal cell carcinoma. Nat Clin Pract Nephrol 2007; 3 (5) 287-293
• 47 Gottschall JL, Neahring B, McFarland JG, Wu GG, Weitekamp LA, Aster RH. Quinine-induced immune thrombocytopenia with hemolytic uremic syndrome: clinical and serological findings in nine patients and review of literature. Am J Hematol 1994; 47 (4) 283-289
• 48 Bougie DW, Birenbaum J, Rasmussen M, Poncz M, Aster RH. Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia. Blood 2009; 113 (5) 1105-1111
• 49 Kojouri K, Vesely SK, George JN. Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes. Ann Intern Med 2001; 135 (12) 1047-1051
• 50 Glynne P, Salama A, Chaudhry A, Swirsky D, Lightstone L. Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic syndrome. Am J Kidney Dis 1999; 33 (1) 133-137
• 51 Christie DJ, Weber RW, Mullen PC, Cook JM, Aster RH. Structural features of the quinidine and quinine molecules necessary for binding of drug-induced antibodies to human platelets. J Lab Clin Med 1984; 104 (5) 730-740
• 52 Park YA, Hay SN, King KE , et al. Is it quinine TTP/HUS or quinine TMA? ADAMTS13 levels and implications for therapy. J Clin Apher 2009; 24 (3) 115-119
• 53 Vesely SK, George JN, Lämmle B , et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003; 102 (1) 60-68