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Thromb Haemost 2000; 84(04): 528-535
DOI: 10.1055/s-0037-1614062
Review Article
Schattauer GmbH

Thrombotic Thrombocytopenic Purpura: A Paradigm Shift?

Douglas B. Cines
1   From the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA
2   The Department of Medicine, University of Pennsylvania, Philadelphia, USA
,
Barbara A. Konkle
1   From the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA
2   The Department of Medicine, University of Pennsylvania, Philadelphia, USA
,
Miha Furlan
3   University Hospital, Inselspital, Bern, Switzerland
› Author Affiliations
Further Information

Publication History

Received 14 April 2000

Accepted after revision 02 May 2000

Publication Date:
11 December 2017 (online)

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Summary

The pathophysiology of thrombotic thrombocytopenic purpura (TTP) has fascinated hematologists for decades. What causes seemingly healthy individuals to suddenly develop widespread platelet-rich microthrombi in specific microvascular beds while sparing other vascular sites completely? Is the disorder caused by the sudden appearance of a novel platelet-agglutinating factor or do platelet-rich thrombi form as a consequence of insult to the capillary endothelium? Is the disease self-limiting, does plasma exchange fundamentally alter the pathophysiology of an autoimmune attack on a normal endothelium, or does the immune response develop to microvasculature that has been perturbed and, if so, by what? It has been thought by many of us that the answers to these questions will provide insight into how platelet-vessel wall interactions are normally regulated in the microvasculature and the differences that characterize the behavior of microvascular, arterial and venous systems in various organs. The corollary to these scientific issues is the anticipation that such answers would also lead to new strategies for intervention in other, more common thrombotic diseases.

 

  • References

  • 1 McCrae KR, Cines DB. (2000) in Hematology. Basic Principles and Practice. Hoffman R, Benz Jr. EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P. eds 3rd Ed. 2126-37 Churchill Livingstone; New York:
  • 2 McCrae KR, Cines DB. Thrombotic microangiopathy in pregnancy. Semin Hematol 1997; 34: 148-58.
    PubMedSearch in Google Scholar
  • 3 Musio F, Bohen EM, Uan CM, Welch PG. Review of thrombotic thrombocytopenic purpura in the setting of systemic lupus erythematosus. Semin Arthritis Rheum 1998; 28: 1-19.
    CrossrefPubMedSearch in Google Scholar
  • 4 Gordon LI, Kwaan HC. Thrombotic microangiopathy manifesting as thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the cancer patient. Semin Thromb Hemost 1999; 25: 217-21.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Lara PN, Coe TL, Zhou H, Fernando L, Holland PV, Wun T. Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Am J Med 1999; 107: 573-9.
    CrossrefPubMedSearch in Google Scholar
  • 6 Hymes KB, Karpatkin S. Human immunodeficiency virus infection and thrombotic microangiopathy. Semin Hematol 1997; 34: 117-25.
    PubMedSearch in Google Scholar
  • 7 Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, yarnold PR, Kwaan HC, Green D. Thrombotic thrombocytopenic purpura. A review of 60 cases. Ann Intern Med 1999; 128: 541-4.
    PubMedSearch in Google Scholar
  • 8 Zeigler ZR, Shadduck RK, Nemunaitis J, Andrews DF, Rosenfeld CS. Bone marrow transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 1995; 15: 247-53.
    PubMedSearch in Google Scholar
  • 9 Leaf AN, Laubensetin 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: 194-7.
    CrossrefPubMedSearch in Google Scholar
  • 10 Yospur LS, Sun NCJ, Figueroa P, Niihara Y. Concurrent thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura in an HIV-positive patient: case report and review of the literature. Am J Hematol 1996; 50: 73-8.
    PubMedSearch in Google Scholar
  • 11 Rarick MU, Espina B, Mocharnuk R, Trilling Y, Levine AM. Thrombotic thrombocytopenic purpura in patients with human immunodeficiency virus infection: A report of three cases and review of the literature. Am J Hematol 1992; 40: 103-9.
    CrossrefPubMedSearch in Google Scholar
  • 12 Doll DC, Yarbro JW. Vascular toxicity associated with antineoplastic agents. Semin Oncol 1992; 19: 580-96.
    PubMedSearch in Google Scholar
  • 13 Moake JL, Byrnes JJ. Thrombotic microangiopathies associated with drugs and bone marrow transplantation. Hematol Oncol Clin North Am 1997; 10: 485-97.
    PubMedSearch in Google Scholar
  • 14 Gordon LI, Kwaan HC. Cancer- and drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol 1997; 34: 140-7.
    PubMedSearch in Google Scholar
  • 15 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: 539-44.
    CrossrefPubMedSearch in Google Scholar
  • 16 Gottschall JL, Neahring B, McFarland JG, Wu G-G, Weitekamp LA, Aster RH. Quinine-induced immune thrombocytopenia with hemolytic uremic syndrome: Clinical and serological findings in nine patients and review of the literature. Am J Hematol 1994; 47: 283-9.
    CrossrefPubMedSearch in Google Scholar
  • 17 Glynne P, Salama A, Chaudhry A, Swirsky D, Lightstone L. Quinineinduced immend thrombocytopenic purpura followed by hemolytic uremic syndrome. Am J Kidney Dis 1999; 33: 133-7.
    CrossrefPubMedSearch in Google Scholar
  • 18 Page Y, Tardy B, Zeni F, Comtete C, Terrana R, Bertrand JC. Thrombotic thrombocytopenic purpura related to ticlopidine. Lancet 1991; 337: 774-6.
    CrossrefPubMedSearch in Google Scholar
  • 19 Wykowski DK, Bascanyi J. Blood dyscrasias and hematologic reactions in ticlopidine users. J Am Med Ass 1996; 276: 952-5.
    PubMedSearch in Google Scholar
  • 20 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: 2524-8.
    CrossrefPubMedSearch in Google Scholar
  • 21 Steinbuhl SR, Tan WA, Foody JM, Topol EJ. Incidence and clinical course of thrombocytic thrombocytopenic purpura due to ticlopidine following coronary stenting. JAMA 1999; 281: 806-10.
    CrossrefPubMedSearch in Google Scholar
  • 22 Bennett C, Connors JM, Carwile JM. et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000 In Press.
    PubMedSearch in Google Scholar
  • 23 Bombeli T, Muller M, Straub PW, Haeberli A. Cyclosporin-induced detachment of vascular endothelial cells initiates the intrinsic coagulation system in plasma and whole blood. J Lab Clin Med 1996; 127: 621-34.
    CrossrefPubMedSearch in Google Scholar
  • 24 Pettit AR, Clark RE. Thrombotic microangiopathy following bone marrow transplantation. Bone Marrow Transplant 1994; 14: 495-504.
    PubMedSearch in Google Scholar
  • 25 Paquette RL, Tran L, Landaw EM. Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graftversus-host disease prophylaxis. Bone Marrow Transplant 1998; 22: 351-7.
    CrossrefPubMedSearch in Google Scholar
  • 26 Tezcan H, Zimmer W, Fenstermaker R, Herzig GP, Schriber J. Severe cerebellar swelling and thrombotic thrombocytopenic purpura associated with FK506. Bone Marrow Transplant 1998; 21: 105-9.
    CrossrefPubMedSearch in Google Scholar
  • 27 Matsuda Y, Hara J, Miyoshi H. et al. Thrombotic microangiopathy associated with reactivation of herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children. Bone Marrow Transplant 1999; 24: 919-23.
    CrossrefPubMedSearch in Google Scholar
  • 28 Zeigler ZR, Rosenfeld CS, Andrews III DF. et al. Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). Am J Hematol 1996; 53: 213-20.
    CrossrefPubMedSearch in Google Scholar
  • 29 Anthony MT, Zeigler ZR, Lister J. et al. Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation. Am J Hematol 1998; 59: 9-14.
    CrossrefPubMedSearch in Google Scholar
  • 30 Zeigler ZR, Kelton JG, Moore JC. et al. Calpain activity in bone marrow transplant-associated thrombotic thrombocytopenic purpura. Bone Marrow Transplant 1999; 24: 641-5.
    CrossrefPubMedSearch in Google Scholar
  • 31 Rabinow SN, Soiffer RJ, Tarbell NJ. et al. Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies. Blood 1991; 77: 1837-44.
    PubMedSearch in Google Scholar
  • 32 Chown SR, Goulden N, Cornish JM, Oakhill A, Pamphilon D, Potter MN. The role of plasma exchange for TTP/HUS post-bone marrow transplant. Bone Marrow Transplant 1996; 17: 897-8.
    PubMedSearch in Google Scholar
  • 33 Ziegler ZR, Shadduck RK, Nath R, Andrews III DF. Pilot study of combined cryosupernatant and protein A immunoadsorbtion exchange in the treatment of grade 3-4 bone marrow transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 1996; 17: 81-6.
    PubMedSearch in Google Scholar
  • 34 Sarode R, McFarland JG, Flomenberg N. et al. Therapeutic plasma exchange does not appear to be effective in the management of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplant 1995; 16: 271-5.
    PubMedSearch in Google Scholar
  • 35 van Okik H, Biesma DH, Fijmheer R. et al. Cyclosporin for thrombotic thrombocytopenic purpura after autologous bone marrow transplantation. Br J Haematol 1997; 96: 641-3.
    CrossrefPubMedSearch in Google Scholar
  • 36 Ahn YS, Jy W, Kolodny L. et al. Activated platelet aggregates in thrombotic thrombocytopenic purpura: decrease with plasma infusions and normalization in remission. Br J Haematol 1996; 95: 408-15.
    CrossrefPubMedSearch in Google Scholar
  • 37 Smith B, Rinder HM. Interaction of platelet and endothelial cells with erythrocytes and leukocytes in thrombotic thrombocytopenic purpura. Semin Hematol 1997; 34: 90-7.
    PubMedSearch in Google Scholar
  • 38 Galli M, Grassi A, Barbui T. Platelet-derived microparticles in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Thromb Haemost 1996; 75: 427-31.
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Moake JL. Studies on the pathophysiology of thrombotic thrombocytopenic purpura. Semin Hematol 1997; 34: 83-9.
    PubMedSearch in Google Scholar
  • 40 Consonni R, Falanga A, Barbui T. Further characterization of plateletaggregating cysteine proteinase activity in thrombotic thrombocytopenic purpura. Br J Haematol 1994; 87: 321-4.
    CrossrefPubMedSearch in Google Scholar
  • 41 Kelton J, Moore JC, Warkentin TE, Hayward CPM. Isolation and characterization of cysteine proteinase in thrombotic thrombocytopenic purpura. Br J Haematol 1996; 93: 421-6.
    CrossrefPubMedSearch in Google Scholar
  • 42 Moake J, Rudy C, Troll J. et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 1982; 307: 1432-5.
    CrossrefPubMedSearch in Google Scholar
  • 43 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-90.
    CrossrefPubMedSearch in Google Scholar
  • 44 Tsai HM, Nagel RL, Hatcher VB, Sussman II. Multimeric composition of endothelial cell-derived von Willebrand factor. Blood 1989; 73: 2074-6.
    PubMedSearch in Google Scholar
  • 45 Moake JL, Turner NA, Stathpoulos NA, Nolasco LH, Hellums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stressinduced platelet aggregation. J Clin Invest 1986; 78: 1456-61.
    CrossrefPubMedSearch in Google Scholar
  • 46 Zimmerman TS, Dent JA, Ruggeri ZM, Nannini LH. Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE). J Clin Invest 1986; 77: 947-51.
    CrossrefPubMedSearch in Google Scholar
  • 47 Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest 1991; 88: 774-82.
    CrossrefPubMedSearch in Google Scholar
  • 48 Furlan M, Robles R, Affolter D, Meyer D, Baillod P, Lämmle B. Triplet structure of von Willebrand factor reflects proteolytic degradation of high molecular weight multimers. Proc Natl Acad Sci USA 1993; 90: 7503-7.
    CrossrefPubMedSearch in Google Scholar
  • 49 Dent JA, Berkowitz SD, Ware J, Kasper CK, Ruggeri ZM. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand disease. Proc Natl Acad Sci USA 1990; 87: 6306-10.
    CrossrefPubMedSearch in Google Scholar
  • 50 Furlan M, Robles R, Lämmle BL. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 1996; 87: 4223-34.
    PubMedSearch in Google Scholar
  • 51 Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood 1996; 87: 4235-44.
    PubMedSearch in Google Scholar
  • 52 Furlan M, Robles R, Solenthaler M, Wassmer M, Sandoz P, Lämmle BL. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood 1997; 89: 3097-103.
    PubMedSearch in Google Scholar
  • 53 Furlan M, Robles R, Morselli B, Sandoz P, Lämmle BL. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 1999; 81: 8-13.
    Thieme ConnectPubMedSearch in Google Scholar
  • 54 Furlan M, Robles R, Galbusera M. et al. Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339: 1578-84.
    CrossrefPubMedSearch in Google Scholar
  • 55 Moake JL, Chintagumpala M, Turner N. et al. Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of chronic relapsing thrombotic thrombocytopenic purpura. Blood 1994; 84: 490-7.
    PubMedSearch in Google Scholar
  • 56 Furlan M, Robles R, Solenthaler M, Lämmle BL. Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood 1998; 91: 2839-46.
    CrossrefPubMedSearch in Google Scholar
  • 57 Tsai H-M, Lian EC-Y. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339: 1585-94.
    CrossrefPubMedSearch in Google Scholar
  • 58 van der Plas RM, Schiphorst ME, Huizinga EG. et al. von Willebrand factor proteolysis is deficient in classic, but not in bone marrow-associated thrombotic thrombocytopenic purpura. Blood 1999; 93: 3798-3802.
    PubMedSearch in Google Scholar
  • 58a 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 Int Med 2000; 132: 794-9.
    PubMedSearch in Google Scholar
  • 59 Gerritsen H, Turecek P, Schwarz HP, Lämmle BL, Furlan M. Assay of von Willebrand factor (vWF)-cleaving protease based on decreased collagen binding affinity of degraded vWF. A tool for the diagnosis of thrombotic thrombocytopenic purpura (TTP). Thromb Haemost 1999; 82: 1386-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 60 Obert B, Tout H, Veyradier A, Fressinaud E, Meyer D, Girma JP. Estimation of the von Willebrand factor-cleaving protease in plasma using monoclonal antibodies to vWF. Thromb Haemost 1999; 82: 1382-5.
    Thieme ConnectPubMedSearch in Google Scholar
  • 61 Fessler BJ. Thrombotic syndromes and autoimmune diseases. Rheumatol Clin N Amer 1997; 23: 461-79.
    PubMedSearch in Google Scholar
  • 62 Leung D, Havens P, Moake J, Kim M, Pober J. Lytic anti-endothelial cell antibodies in haemolytic-uremic syndrome. Lancet 1988; 02: 183-6.
    PubMedSearch in Google Scholar
  • 63 Burns ER, Zucker-Franklin D. Pathologic effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells. Blood 1982; 60: 1030-7.
    PubMedSearch in Google Scholar
  • 64 Tandon NN, Rock G, Jamieson GA. Anti-CD36 antibodies in thrombotic thrombocytopenic purpura. Br J Haematol 1994; 88: 816-25.
    CrossrefPubMedSearch in Google Scholar
  • 65 Schultz DR, Arnold PI, Jy W. et al. Anti-CD36 autoantibodies in thrombotic thrombocytopenic purpura and other thrombotic disorders: identification of an 85 kD form of CD36 as a target antigen. Br J Haematol 1998; 103: 849-57.
    CrossrefPubMedSearch in Google Scholar
  • 66 Wright JF, Wang H, Hornstein A. et al. Characterization of platelet glycoproteins and platelet/endothelial cell antibodies in patients with thrombotic thrombocytopenic purpura. Br J Haematol 1999; 107: 546-55.
    CrossrefPubMedSearch in Google Scholar
  • 67 Rock G, Kelton JG, Shumak KH. et al. Laboratory abnormalities in the thrombotic thrombocytopenic purpura. Br J Haematol 1998; 103: 1031-6.
    CrossrefPubMedSearch in Google Scholar
  • 68 Raife TJ, Atkinson B, Aster RH, McFarland JG, Gottschall JL. Minimal evidence of platelet and endothelial cell reactive antibodies in thrombotic thrombocytopenic purpura. Am J Hematol 1999; 62: 82-7.
    CrossrefPubMedSearch in Google Scholar
  • 69 Koenig DW, Barley-Maloney L, Daniel TO. A western blot assay detects autoantibodies to cryptic endothelial antigens in thrombotic microangiopathies. J Clin Immunol 1993; 13: 204-11.
    CrossrefPubMedSearch in Google Scholar
  • 70 Rock G, Chauhan K, Jamieson GA, Tandon NN. Anti-CD36 antibodies in patients with lupus anticoagulants and thrombotic complications. Br J Haematol 1994; 88: 878-80.
    CrossrefPubMedSearch in Google Scholar
  • 71 He R, Reid DM, Jones CE, Shulman NR. Spectrum of Ig classes, specificities, and titers of serum glycoproteins in chronic idiopathic thrombocytopenic purpura. Blood 1994; 83: 1924-32.
    PubMedSearch in Google Scholar
  • 72 Weisenburger DD, O’Conner ML, Hart N. Thrombotic thrombocytopenic purpura with C’3 vascular deposits. Am J Clin Pathol 1977; 67: 61-3.
    CrossrefPubMedSearch in Google Scholar
  • 73 Brittingham III TE, Chaplin Jr H. Attempted passive transfer of thrombotic thrombocytopenic purpura. Blood. 1956: 480-3.
    Search in Google Scholar
  • 74 Lefevre P, George F, Durand JM, Sampol J. Detection of circulating endothelial cells in thrombotic thrombocytopenic purpura. Thromb Haemost 1993; 69: 522.
    Thieme ConnectPubMedSearch in Google Scholar
  • 75 Noris M, Ruggenenti P, Perna A. et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: Role of factor H abnormalities. J Am Soc Nephrol 1999; 10: 281-93.
    PubMedSearch in Google Scholar
  • 76 Stefanec T. Endothelial apoptosis. Could it have a role in the pathogenesis and treatment of disease?. Chest 2000; 117: 841-54.
    CrossrefPubMedSearch in Google Scholar
  • 77 Laurence J, Mitra D, Steiner M, Staiano-Coico L, Jaffe E. Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells. Blood 1996; 87: 3245-54.
    PubMedSearch in Google Scholar
  • 78 Wu X-W, Li Q-Z, Lian EC-Y. Plasma from a patient with thrombotic thrombocytopenic purpura induces endothelial cell apoptosis and platelet aggregation. Thromb Res 1999; 93: 79-87.
    CrossrefPubMedSearch in Google Scholar
  • 79 Mitra D, Jaffe EA, Weksler B, Hajjar KA, Doserland C, Laurence J. Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells. Blood 1997; 89: 1224-34.
    PubMedSearch in Google Scholar
  • 80 Mitra D, Kim J, MacLow C, Karsan A, Laurence J. Role of caspases 1 and 3 and Bcl-2-related molecules in endothelial cell apoptosis associated with thrombotic microangiopathies. Am J Hematol 1998; 59: 279-87.
    CrossrefPubMedSearch in Google Scholar
  • 81 Dang CT, Magid MS, Weksler B, Chadburn A, Laurence J. Enhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura. Blood 1999; 93: 1264-70.
    PubMedSearch in Google Scholar
  • 82 Torok TJ, Holman RC, Chorba TL. Increasing mortality from thrombotic thrombocytopenic purpura in the United States – Analysis of national mortality data, 1968-1991. Am J Hematol 1995; 50: 84-90.
    CrossrefPubMedSearch in Google Scholar
  • 83 Hayward CPM, Sutton DMC, Carter Jr. WH. et al. Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Arch Intern Med 1994; 154: 982-7.
    CrossrefPubMedSearch in Google Scholar
  • 84 Sarode R, Gottschall JL, Aster RH, McFarland JG. Thrombotic thrombocytopenic purpura: Early and late responders. Am. J. Hematol 1997; 54: 102-7.
    CrossrefPubMedSearch in Google Scholar
  • 85 Colflesh CR, Agarwal R, Knochel JP. Timing of plasma exchange therapy for thrombotic thrombocytopenic purpura: A brief clinical observation. Am J Med Sci 1996; 311: 167-8.
    PubMedSearch in Google Scholar
  • 86 Rock GA, Shumak KH, Buskard NA. et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991; 325: 393-7.
    CrossrefPubMedSearch in Google Scholar
  • 87 Rock G, Shumak KH, Sutton DMC, Buskard NA, Nair RC, Group atMotCA. Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura. Br J Haematol 1996; 94: 383-6.
    CrossrefPubMedSearch in Google Scholar
  • 88 Rock GA. Management of thrombotic thrombocytopenic purpura. Br J Haematol 2000; 109: 496-507.
    CrossrefPubMedSearch in Google Scholar
  • 89 Evans G, Llewelyn C, Luddington R, Baglin TP, Williamson LM. Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura. Clin Lab Haem 1999; 21: 119-23.
    CrossrefPubMedSearch in Google Scholar
  • 90 Harrison CN, Lawrie AS, Iqbal A, Hunter A, Machin SJ. Plasma exchange with solvent/detergent-treated plasma of resistant thrombotic thrombocytopenic purpura. Br J Haematol 1996; 94: 756-8.
    CrossrefPubMedSearch in Google Scholar
  • 91 Pehta JC. Clinical studies with solvent-detergent treated products. Transfus Med Rev 1996; X: 303-11.
    PubMedSearch in Google Scholar
  • 92 Mast AE, Stadanlick JE, Lockettt JM, Dietzen DJ. Solvent/detergenttreated plasma has decreased antitrypsin activity and absent antiplasmin activity. Blood 1999; 94: 3922-7.
    PubMedSearch in Google Scholar
  • 93 Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 cases. N Engl J Med 1991; 325: 398-403.
    CrossrefPubMedSearch in Google Scholar
  • 94 Porta C, Cemturioni R, Vianeli N. et al. Thrombotic thrombocytopenic purpura and relapses. Why do case series differ?. Am J Hematol 1996; 52: 215-6.
    CrossrefPubMedSearch in Google Scholar
  • 95 Kwaan HC, Soff GA. Management of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol 1997; 34: 159-66.
    PubMedSearch in Google Scholar
  • 96 Häberle J, Kehrel B, Ritter J, Jurgens H, Lämmle BL, Furlan M. New strategies in diagnosis and treatment of thrombotic thrombocytopenic purpura. Eur J Pediatr 1999; 158: 883-7.
    CrossrefPubMedSearch in Google Scholar
  • 97 Wada H, Mori Y, Shimura M. et al. Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular injuries. Am J Hematol 1998; 58: 189-94.
    CrossrefPubMedSearch in Google Scholar
  • 98 Ellis J, Theodossious C, Schwarzenberger P. Treatment of thrombotic thrombocytopenic purpura with the cryosupernatant fraction of plasma: A case report and review of the literature. Am J Med Sci 1999; 318: 190-3.
    CrossrefPubMedSearch in Google Scholar
  • 99 Gaddis TG, Guthrie Jr. TH, Drew MJ, Sahud M, Howe RB, Mittelman A. Treatment of plasma refractory thrombotic thrombocytopenic purpura with protein A immunoabsorption. Am J Hematol 1997; 55: 55-8.
    CrossrefPubMedSearch in Google Scholar
  • 100 Perez-Sanchez I, Anguita J, Pintado T. Use of cyclophosphamide in the treatment of thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus: report of two cases. Ann Hematol 1999; 78: 285-7.
    CrossrefPubMedSearch in Google Scholar
  • 101 Zappasodi P, Corso A, Castagnola C, Tajana M, Lunghi M, Bernasconi C. A successful combination of plasma exchange and intravenous cyclophosphamide in a patient with a refractory thrombotic thrombocytopenic purpura. Eur J Haematol 1999; 62: 278-9.
    PubMedSearch in Google Scholar
  • 102 Kierdorf H, Maurin N, Heintz B. Cyclosporine for thrombotic thrombocytopenic purpura. Ann Intern Med 1992; 118: 987-8.
    PubMedSearch in Google Scholar
  • 103 Hand JP, Lawlor ER, Yong CKK, Davis JH. Successful use of cyclosporine A in the treatment of refractory thrombocytopenic purpura. Br J Haematol 1998; 100: 597-9.
    CrossrefPubMedSearch in Google Scholar
  • 104 Pasquale D, Vidhya R, DaSilva K, Tsan M-F, Lansing L, Chikkappa G. Chronic relapsing thrombotic thrombocytopenic purpura: Role of therapy with cyclosporine. Am J Hematol 1998; 57: 57-61.
    CrossrefPubMedSearch in Google Scholar
  • 105 Spiekermann K, Wormann B, Rumpf K-W, Hideemann W. Combination chemotherapy with CHOP for recurrent thrombotic thrombocytopenic purpura. Br J Haematol 1997; 97: 544-6.
    CrossrefPubMedSearch in Google Scholar
  • 106 Musso M, Porretto F, Crescimanno A. et al. Successful treatment of resistant thrombotic thrombocytopenic purpura/hemolytic uremic syndrome with autologous peripheral blood stem and progenitor (CD34+) cell transplantation. Bone Marrow Transplant 1999; 24: 207-9.
    CrossrefPubMedSearch in Google Scholar
  • 107 Creager AJ, Brecher ME, Bandarenko N. Thrombotic thrombocytopenic purpura that is refractory to therapeutic exchange in two patients with occult infection. Transfusion 1998; 38: 419-23.
    CrossrefPubMedSearch in Google Scholar
  • 108 Saracco SM, Farhri DC. Splenic Pathology in Thrombotic Thrombocytopenic Purpura. Am J Surg Pathol 1990; 14: 223-9.
    CrossrefPubMedSearch in Google Scholar
  • 109 Cuttner J. Thrombotic thrombocytopenic purpura: A ten-year experience. Blood 1980; 56: 302-6.
    PubMedSearch in Google Scholar
  • 110 Winslow GA, Nelson EW. Thrombotic thrombocytopenic purpura: Indications for and results of splenectomy. Am J Surg 1995; 170: 558-63.
    CrossrefPubMedSearch in Google Scholar
  • 111 Thompson CE, Damon LE, Ries CA, Linker CA. Thrombotic microangiopathy in the 1980’s: Clinical features, response to treatment, and the impact of the human immunodeficiency virus epidemic. Blood 1992; 80: 1890-5.
    CrossrefPubMedSearch in Google Scholar
  • 112 Shumak KH, Rock GA, Nair RC, Group tCA. Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Ann Intern Med 1995; 122: 569-72.
    CrossrefPubMedSearch in Google Scholar
  • 113 Mant MJ, Turner AR, Bruce D, Ritchie C, Larratt LM. Splenectomy during partial remission in thrombotic thrombocytopenic purpura with prolonged plasma exchange dependency. Am J Hematol 1999; 62: 56-7.
    CrossrefPubMedSearch in Google Scholar
  • 114 Veltman GAM, Brand A, Leeksma OC, ten Bosch GJA, van Krieken JHJM, Briet E. The role of splenectomy in the treatment of relapsing thrombotic thrombocytopenic purpura. Ann Hematol 1995; 70: 231-6.
    CrossrefPubMedSearch in Google Scholar
  • 115 Real E, Pastor E, Perella M, Grau E. Elective splenectomy in relapsing thrombotic thrombocytopenic purpura. Haematologica 1998; 83: 959-60.
    PubMedSearch in Google Scholar