Severe Thrombotic Microangiopathy in Critically Ill Patients

  • F. Pene
  • Y. E. Claessens
  • J. P. Mira
Conference paper


Thrombotic microangiopathies (TMA) are uncommon multisystemic microvascular occlusive diseases combining various stages of hematological, renal, and neurological disorders and characterized by a classical pentad: fever, peripheral thrombocytopenia, microangiopathic hemolytic anemia, acute renal failure, and neurological abnormalities. Treatment with exogenous plasma, either through plasma exchange or plasma infusion, has dramatically improved the outcome of the disease. However, most severe patients require monitoring and support in the intensive care unit (ICU) for organ failures, mainly renal, and neurological disorders. This chapter provides recent insights into the pathophysiology of the disease and focuses on treatment management and prognosis of severe TMA.


Plasma Exchange Hemolytic Uremic Syndrome Thrombotic Thrombocytopenic Purpura Thrombotic Microangiopathy Plasma Infusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Rock GA, Shumak KH, Buskard NA, et al (1991) Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 325: 393-397Google Scholar
  2. 2.
    Rock G, Shumak KH, Kelton J, et al (1992) Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group. Transfusion 32: 710-714Google Scholar
  3. 3.
    George JN (2000) How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Blood 96: 1223 - 1229PubMedGoogle Scholar
  4. 4.
    Mead PS, Griffin PM (1998) Escherichia coli O157:H7. Lancet 352: 1207 - 1212PubMedCrossRefGoogle Scholar
  5. 5.
    Carter AO, Borczyk AA, Carlson JA, et al (1987) A severe outbreak of Escherichia coli O157:H7-associated hemorrhagic colitis in a nursing home. N Engl J Med 317: 1496 - 1500PubMedCrossRefGoogle Scholar
  6. 6.
    Hymes KB, Karpatkin S (1997) Human immunodeficiency virus infection and thrombotic microangiopathy. Semin Hematol 34: 117 - 125PubMedGoogle Scholar
  7. 7.
    Gordon LI, Kwaan HC (1999) Thrombotic microangiopathy manifesting as thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the cancer patient Semin Thromb Hemost 25: 217 - 221CrossRefGoogle Scholar
  8. 8.
    McCrae KR, Cines DB (1997) Thrombotic microangiopathy during pregnancy. Semin Hematol 34: 148 - 158PubMedGoogle Scholar
  9. 9.
    Roy V, Rizvi MA, Vesely SK, George JN (2001) Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes. Bone Marrow Transplant 27: 641 - 646PubMedCrossRefGoogle Scholar
  10. 10.
    Torok TJ, Holman RC, Chorba TL (1995) Increasing mortality from thrombotic thrombocytopenic purpura in the United States - analysis of national mortality data, 1968-1991. Am J Hematol 50: 84 - 90PubMedCrossRefGoogle Scholar
  11. 11.
    Clark WF, Rock GA, Buskard N, et al (1999) Therapeutic plasma exchange: an update from the Canadian Apheresis Group, Ann Intern Med 131: 453 - 462PubMedCrossRefGoogle Scholar
  12. 12.
    Dang CT, Magid MS, Weksler B, Chadburn A, Laurence J (1999) Enhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura, Blood 93: 1264 - 1270PubMedGoogle Scholar
  13. 13.
    Tandon NN, Rock G, Jamieson GA (1994) Anti-CD36 antibodies in thrombotic thrombocytopenic purpura. Br J Haematol 88: 816 - 825PubMedCrossRefGoogle Scholar
  14. 14.
    Laurence J, Mitra D, Steiner M, Staiano-Coico L, Jaffe E (1996) Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells. Blood 87: 3245 - 3254PubMedGoogle Scholar
  15. 15.
    Jimenez JJ, Jy W, Mauro LM, Horstman LL, Ahn YS (2001) Elevated endothelial micropartides in thrombotic thrombocytopenic purpura: findings from brain and renal microvascular cell culture and patients with active disease. Br J Haematol 112: 81 - 90PubMedCrossRefGoogle Scholar
  16. 16.
    Morigi M, Galbusera M, Binda E, et al (2001) Verotoxin-l-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 98: 1828 - 1835PubMedCrossRefGoogle Scholar
  17. 17.
    Novak RW, Martin CR, Orsini EN (1983) Hemolytic-uremic syndrome and T-cryptantigen exposure by neuraminidase-producing pneumococci: an emerging problem? Pediatr Pathol 1: 409 - 413PubMedCrossRefGoogle Scholar
  18. 18.
    Noris M, Ruggenenti P, Perna A, et al (1999) Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. J Am Soc Nephrol 10: 281-293Google Scholar
  19. 19.
    Fujikawa K, Suzuki H, McMullen B, Chung D (2001) Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 98: 1662 - 1666PubMedCrossRefGoogle Scholar
  20. 20.
    Gerritsen HE, Robles R, Lammle B, Furlan M (2001) Partial amino acid sequence of purified von Willebrand factor-cleaving protease. Blood 98: 1654 - 1661PubMedCrossRefGoogle Scholar
  21. 21.
    Moake JL, Rudy CK, Troll JH, et al (1982) Unusually large plasma factor VIII: von Wille-brand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 307: 1432 - 1435PubMedCrossRefGoogle Scholar
  22. 22.
    Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD (1986) Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 78: 1456 - 1461PubMedCrossRefGoogle Scholar
  23. 23.
    Furlan M, Robles R, Galbusera M, et al (1998) Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 339: 1578 - 1584PubMedCrossRefGoogle Scholar
  24. 24.
    Tsai HM, Lian EC (1998) Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 339: 1585 - 1594PubMedCrossRefGoogle Scholar
  25. 25.
    Levy GG, Nichols WC, Lian EC, et al (2001) Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413: 488 - 494PubMedCrossRefGoogle Scholar
  26. 26.
    Bianchi V, Robles R, Alberio L, Furlan M, Lammle B (2002) Von Willebrand factor-cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood 100: 710 - 713PubMedCrossRefGoogle Scholar
  27. 27.
    van der Plas RM, Schiphorst ME, Huizinga EG, et al (1999) von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura. Blood 93: 3798 - 3802Google Scholar
  28. 28.
    Veyradier A, Obert B, Houllier A, Meyer D, Girma JP (2001) Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood 98: 1765 - 1772PubMedCrossRefGoogle Scholar
  29. 29.
    Remuzzi G, Galbusera M, Noris M, et al (2002) Von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Blood 100: 778 - 785PubMedCrossRefGoogle Scholar
  30. 30.
    Mannucci PM, Canciani MT, Forza I, Lussana F, Lattuada A, Rossi E (2001) Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 98: 2730 - 2735PubMedCrossRefGoogle Scholar
  31. 31.
    Bell WR, Braine HG, Ness PM, Kidder TS (1991) Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 325: 398 - 403PubMedCrossRefGoogle Scholar
  32. 32.
    Lara PN Jr, Coe TL, Zhou H, Fernando L, Holland PV, Wun T (1999) Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Am J Med 107: 573 - 579PubMedCrossRefGoogle Scholar
  33. 33.
    Allford SL, Harrison P, Lawrie AS, Liesner R, MacKie IJ, Machin SJ (2000) Von Willebrand factor-cleaving protease activity in congenital thrombotic thrombocytopenic purpura. Br J Haematol 111: 1215 - 1222PubMedCrossRefGoogle Scholar
  34. 34.
    Ruggenenti P, Galbusera M, Cornejo RP, Bellavita P, Remuzzi G (1993) Thrombotic thrombocytopenic purpura: evidence that infusion rather than removal of plasma induces remission of the disease. Am J Kidney Dis 21: 314 - 318PubMedGoogle Scholar
  35. 35.
    Rock G, Shumak KH, Sutton DM, Buskard NA, Nair RC (1996) Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura. Members of the Canadian Apheresis Group. Br J Haematol 94: 383-386Google Scholar
  36. 36.
    Henon P (1991) [Treatment of thrombotic thrombopenic purpura. Results of a multicenter randomized clinical study]. Presse Med 20: 1761 - 1767Google Scholar
  37. 37.
    Novitzky N, Jacobs P, Rosenstrauch W (1994) The treatment of thrombotic thrombocytopenic purpura: plasma infusion or exchange? Br J Haematol 87: 317 - 320PubMedCrossRefGoogle Scholar
  38. 38.
    Pene F, Heshmati F, Moreau D, et al (2001) [Thrombotic microangiopathy in ICU: a retrospective multicenter study]. Reanimation 10 (suppl 1):SP 269 (abst)Google Scholar
  39. 39.
    Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WT (1999) Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet 354: 1327 - 1330PubMedCrossRefGoogle Scholar
  40. 40.
    Dundas S, Todd WT, Stewart AI, Murdoch PS, Chaudhuri AK, Hutchinson SJ (2001) The Central Scotland Escherichia coli O157:H7 Outbreak: Risk factors for the hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis 33: 923-931Google Scholar
  41. 41.
    Rock G, Porta C, Bobbio-Pallavicini E (2000) Thrombotic thrombocytopenic purpura treatment in year 2000. Haematologica 85: 410 - 419PubMedGoogle Scholar
  42. 42.
    Coppo P, Bussel A, Adrie C, Alberti C, Le Gall J, Schlemmer B (2001) Early high dose plasma infusion versus plasmapheresis as an emergency treatment of thrombotic microangiopathy. Transf Apher Sci 24:163-164a (abst)Google Scholar
  43. 43.
    Bobbio-Pallavicini E, Gugliotta L, Centurioni R, et al (1997) Antiplatelet agents in thrombotic thrombocytopenic purpura (TTP). Results of a randomized multicenter trial by the Italian Cooperative Group for TTP. Haematologica 82: 429-435Google Scholar
  44. 44.
    Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Yarnold PR, Kwaan HC, Green D (1998) Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60 cases. Ann Intern Med 128: 541 - 544PubMedCrossRefGoogle Scholar
  45. 45.
    Bennett CL, Connors JM, Carwile JM, et al (2000) Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 342: 1773 - 1777PubMedCrossRefGoogle Scholar
  46. 46.
    Tarantolo SR, Landmark JD, Iwen PC, Kessinger A, Chan WC, Hinrichs SH (1997) Bartonella-like erythrocyte inclusions in thrombotic thrombocytopenic purpura. Lancet 350: 1602PubMedCrossRefGoogle Scholar
  47. 47.
    Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI (2000) The risk of the hemolyticuremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342: 1930 - 1936PubMedCrossRefGoogle Scholar
  48. 48.
    Safdar N, Said A, Gangnon RE, Maki DG (2002) Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA 288: 9961001Google Scholar
  49. 49.
    Chandler WL, Jelacic S, Boster DR, et al (2002) Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N Engl J Med 346: 23 - 32PubMedCrossRefGoogle Scholar
  50. 50.
    Raife TJ, Lentz SR, Atkinson BS, Vesely SK, Hessner MJ (2002) Factor V Leiden: a genetic risk factor for thrombotic microangiopathy in patients with normal von Willebrand factor-cleaving protease activity. Blood 99: 437 - 442PubMedCrossRefGoogle Scholar
  51. 51.
    Harkness DR, Byrnes JJ, Lian EC, Williams WD, Hensley GT (1981) Hazard of platelet transfusion in thrombotic thrombocytopenic purpura. JAMA 246: 1931 - 1933PubMedCrossRefGoogle Scholar
  52. 52.
    McCarthy LJ, Danielson CF, Graves V (1994) Do platelet transfusions to patients with TTP influence their survival? Blood 84 (suppl 1 ): 669a (abst)Google Scholar
  53. 53.
    Rose M, Eldor A (1987) High incidence of relapses in thrombotic thrombocytopenic purpura. Clinical study of 38 patients. Am J Med 83: 437 - 444PubMedCrossRefGoogle Scholar
  54. 54.
    Sarode R, Gottschall JL, Aster RH, McFarland JG (1997) Thrombotic thrombocytopenic purpura: early and late responders. Am J Hematol 54: 102 - 107PubMedCrossRefGoogle Scholar
  55. 55.
    Patton JF, Manning KR, Case D, Owen J (1994) Serum lactate dehydrogenase and platelet count predict survival in thrombotic thrombocytopenic purpura. Am J Hematol 47: 94 - 99PubMedCrossRefGoogle Scholar
  56. 56.
    Pereira A, Mazzara R, Monteagudo J, et al (1995) Thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange. Ann Hematol 70: 319 - 323PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • F. Pene
  • Y. E. Claessens
  • J. P. Mira

There are no affiliations available

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