Semin Thromb Hemost 2013; 39(02): 153-160
DOI: 10.1055/s-0032-1333538
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of Patients with Microangiopathic Hemolytic Anemia and Thrombocytopenia

James N. George
1   Department of Biostatistics and Epidemiology, College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
2   Department of Medicine, College of Medicine, Hematology-Oncology Section, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
,
Roseleen S. Charania
2   Department of Medicine, College of Medicine, Hematology-Oncology Section, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
› Author Affiliations
Further Information

Publication History

Publication Date:
06 February 2013 (online)

Abstract

When a patient presents with unexpected microangiopathic hemolytic anemia and thrombocytopenia, the diagnosis of thrombotic thrombocytopenic purpura (TTP) is often considered. However, many different disorders, including many different systemic infections and malignancies, can cause thrombotic microangiopathy (TMA), with the clinical features of microangiopathic hemolytic anemia and thrombocytopenia. Other etiologies include severe hypertension, preeclampsia, systemic lupus erythematosus, adverse drug reactions, allogeneic hematopoietic stem cell transplantation, and abnormalities of complement regulation. This article focuses on distinguishing TTP from other etiologies of microangiopathic hemolytic anemia and thrombocytopenia, because consideration of the diagnosis of TTP requires an urgent decision for the initiation of plasma exchange treatment. Awareness of the many etiologies of TMA is essential for the appropriate evaluation of patients presenting with microangiopathic hemolytic anemia and thrombocytopenia and the appropriate diagnosis of TTP.

 
  • References

  • 1 Symmers WS. Thrombotic microangiopathic haemolytic anaemia (thrombotic microangiopathy). BMJ 1952; 2 (4790) 897-903
  • 2 Brain MC, Dacie JV, Hourihane DO. Microangiopathic haemolytic anaemia: the possible role of vascular lesions in pathogenesis. Br J Haematol 1962; 8: 358-374
  • 3 Rock GA, Shumak KH, Buskard NA , et al. Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991; 325 (6) 393-397
  • 4 Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45: 139-159
  • 5 George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116 (20) 4060-4069
  • 6 Som S, Deford CC, Kaiser ML , et al. Decreasing frequency of plasma exchange complications in patients treated for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 1996 to 2011. Transfusion 2012; 52 (12) 2525-2532
  • 7 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
  • 8 Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115 (8) 1500-1511 , quiz 1662
  • 9 George JN, Chen Q, Deford CC, Al-Nouri ZL. Ten patient stories illustrating the extraordinarily diverse clinical features of patients with thrombotic thrombocytopenic purpura and severe ADAMTS13 deficiency. J Clin Apher 2012; 27 (6) 302-311
  • 10 Tsai H-M. Is severe deficiency of ADAMTS-13 specific for thrombotic thrombocytopenic purpura? Yes. J Thromb Haemost 2003; 1 (4) 625-631
  • 11 Bentley MJ, Lehman CM, Blaylock RC, Wilson AR, Rodgers GM. The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange. Transfusion 2010; 50 (8) 1654-1664
  • 12 George JN. Forecasting the future for patients with hereditary TTP. Blood 2012; 120 (2) 243-244
  • 13 Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365 (9464) 1073-1086
  • 14 Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361 (17) 1676-1687
  • 15 Booth KK, Terrell DR, Vesely SK, George JN. Systemic infections mimicking thrombotic thrombocytopenic purpura. Am J Hematol 2011; 86 (9) 743-751
  • 16 George JN, Al-Nouri ZL. Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes. Hematology (Am Soc Hematol Educ Program) 2012; 604-609
  • 17 Kosugi N, Tsurutani Y, Isonishi A, Hori Y, Matsumoto M, Fujimura Y. Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor. Intern Med 2010; 49 (7) 689-693
  • 18 George JN. The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 2003; 10 (5) 339-344
  • 19 Vesely SK, Li X, McMinn JR, Terrell DR, George JN. Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion 2004; 44 (8) 1149-1158
  • 20 Robertson MD, Zumberg M. Post-appendectomy thrombotic thrombocytopenic purpura: a case report and review of the literature. Am J Hematol 2007; 82 (3) 224-228
  • 21 Swisher KK, Doan JT, Vesely SK , et al. Pancreatitis preceding acute episodes of thrombotic thrombocytopenic purpura: report of five patients with a systematic review of the literature. Haematologica 2007; 92: 936-943
  • 22 Leaf AN, Laubenstein LJ, Raphael B, Hochster H, Baez L, Karpatkin S. Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus type 1 (HIV-1) infection. Ann Intern Med 1988; 109 (3) 194-197
  • 23 Gunther K, Garizio D, Nesara P. ADAMTS13 activity and the presence of acquired inhibitors in human immunodeficiency virus-related thrombotic thrombocytopenic purpura. Transfusion 2007; 47 (9) 1710-1716
  • 24 Benjamin M, Terrell DR, Vesely SK , et al. Frequency and significance of HIV infection among patients diagnosed with thrombotic thrombocytopenic purpura. Clin Infect Dis 2009; 48 (8) 1129-1137
  • 25 Brecher ME, Hay SN, Park YA. Is it HIV TTP or HIV-associated thrombotic microangiopathy?. J Clin Apher 2008; 23 (6) 186-190
  • 26 Froehlich-Zahnd R, George JN, Vesely SK , et al. Evidence for a role of anti-ADAMTS13 autoantibodies despite normal ADAMTS13 activity in recurrent thrombotic thrombocytopenic purpura. Haematologica 2012; 97 (2) 297-303
  • 27 Karpac CA, Li X, Terrell DR , et al. Sporadic bloody diarrhoea-associated thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome: an adult and paediatric comparison. Br J Haematol 2008; 141 (5) 696-707
  • 28 Buchholz U, Bernard H, Werber D , et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 2011; 365 (19) 1763-1770
  • 29 Karpac CA, Lee A, Kunnel BS, Bamgbola OF, Vesely SK, George JN. Endemic Esherichia coil O157:H7 infections and hemolytic-uremic syndrome in Oklahoma, 2002-2005. J Okla State Med Assoc 2007; 100 (11) 429-433
  • 30 George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354 (18) 1927-1935
  • 31 George JN. Systemic malignancies as a cause of unexpected microangiopathic hemolytic anemia and thrombocytopenia. Oncology (Williston Park) 2011; 25 (10) 1-8
  • 32 Francis KK, Kalyanam N, Terrell DR, Vesely SK, George JN. Disseminated malignancy misdiagnosed as thrombotic thrombocytopenic purpura: a report of 10 cases and a systematic review of the literature. Oncologist 2007; 12: 11-19
  • 33 Antman KH, Skarin AT, Mayer RJ, Hargreaves HK, Canellos GP. Microangiopathic hemolytic anemia and cancer: a review. Medicine (Baltimore) 1979; 58 (5) 377-384
  • 34 Francis KK, Kojouri K, George JN. Occult systemic carcinoma masquerading as thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Community Oncol 2005; 2: 339-343
  • 35 Zhang B, Xing C, Yu X, Sun B, Zhao X, Qian J. Renal thrombotic microangiopathies induced by severe hypertension. Hypertens Res 2008; 31 (3) 479-483
  • 36 Boctor FN, Prichard JW. Kidney involvement in thrombotic thrombocytopenic purpura and malignant hypertension. Transfusion 2009; 49 (9) 1783-1784
  • 37 Egan JA, Bandarenko N, Hay SN , et al. Differentiating thrombotic microangiopathies induced by severe hypertension from anemia and thrombocytopenia seen in thrombotic thrombocytopenia purpura. J Clin Apher 2004; 19 (3) 125-129
  • 38 Cooling LL, Gay S, Silver S. Transfusion medicine illustrated: An imPRESsive mimic. Transfusion 2010; 50 (1) 11-12
  • 39 McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher 2001; 16 (4) 202-209
  • 40 George JN, Vesely SK, James JA. Overlapping features of thrombotic thrombocytopenic purpura and systemic lupus erythematosus. South Med J 2007; 100 (5) 512-514
  • 41 Terrell DR, Vesely SK, Kremer Hovinga JA, Lämmle B, George JN. Different disparities of gender and race among the thrombotic thrombocytopenic purpura and hemolytic-uremic syndromes. Am J Hematol 2010; 85 (11) 844-847
  • 42 Stroncek DF, Vercellotti GM, Hammerschmidt DE, Christie DJ, Shankar RA, Jacob HS. Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. Blood 1992; 80 (1) 241-248
  • 43 Gottschall JL, Elliot W, Lianos E, McFarland JG, Wolfmeyer K, Aster RH. Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome: a new clinical entity. Blood 1991; 77 (2) 306-310
  • 44 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
  • 45 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
  • 46 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
  • 47 Humphreys BD, Sharman JP, Henderson JM , et al. Gemcitabine-associated thrombotic microangiopathy. Cancer 2004; 100 (12) 2664-2670
  • 48 Said T, Al-Otaibi T, Al-Wahaib S , et al. Posttransplantation calcineurin inhibitor-induced hemolytic uremic syndrome: single-center experience. Transplant Proc 2010; 42 (3) 814-816
  • 49 Eremina V, Jefferson JA, Kowalewska J , et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358 (11) 1129-1136
  • 50 Sartelet H, Toupance O, Lorenzato M , et al. Sirolimus-induced thrombotic microangiopathy is associated with decreased expression of vascular endothelial growth factor in kidneys. Am J Transplant 2005; 5 (10) 2441-2447
  • 51 Leach JW, Pham T, Diamandidis D, George JN. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) following treatment with deoxycoformycin in a patient with cutaneous T-cell lymphoma (Sezary syndrome): a case report. Am J Hematol 1999; 61 (4) 268-270
  • 52 Elliott MA, Nichols Jr WL, Plumhoff EA , et al. Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review. Mayo Clin Proc 2003; 78 (4) 421-430
  • 53 Siami K, Kojouri K, Swisher KK, Selby GB, George JN, Laszik ZG. Thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation: an autopsy study. Transplantation 2008; 85 (1) 22-28
  • 54 George JN. Hematopoietic stem cell transplantation-associated thrombotic microangiopathy: defining a disorder. Bone Marrow Transplant 2008; 41 (11) 917-918
  • 55 Ho VT, Cutler C, Carter S , et al. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11 (8) 571-575
  • 56 Ruutu T, Barosi G, Benjamin RJ , et al. European Group for Blood and Marrow Transplantation; European LeukemiaNet. Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group. Haematologica 2007; 92 (1) 95-100
  • 57 Nester C, Stewart Z, Myers D , et al. Pre-emptive eculizumab and plasmapheresis for renal transplant in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 2011; 6 (6) 1488-1494