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von Willebrand Factor—Cleaving Protease and Upshaw-Schulman Syndrome

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Abstract

Vascular endothelial cell (EC)-produced plasma von Willebrand factor (vWF) plays a critical role in primary hemostasis through its action of anchoring platelets onto the injured denuded subendothelial matrices under high shear stress. Unusually large vWF multimers (UL-vWFMs), present in plasma immediately after release from ECs, are most biologically active, but they are soon cleaved and degraded into smaller vWFMs by a specific plasma protease, termed vWF-cleaving protease (vWF-CPase), in normal circulation. Recent studies on the relationship between UL-vWFMs and vWF-CPase, together with its autoantibody (inhibitor) have brought about a clear discrimination between thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Furthermore, a congenital deficiency of this enzyme activity has been shown to cause Upshaw-Schulman syndrome, a complex constitutional bleeding diathesis. Successful purification of vWF-CPase revealed that this enzyme is composed of a single polypeptide with a molecular mass of approximately 190 kd, and its complementary DNA cloning unambiguously indicated that it is uniquely produced in the liver and its gene is located on chromosome 9q34. The messenger RNA of vWF-CPase had a span of 4.6 kb, and its enzyme was designated ADAMTS 13. The predicted complete amino acid sequence of this enzyme consisted of 1427 residues, including a signal peptide, a short propeptide terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat (TSP1), a cysteine-rich domain, an ADAMTS spacer, 7 additional TSP1 repeats, and 2 CUB domains.

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References

  1. Bloom AL, Giddings JC, Wilke CJ. Factor VIII on the vascular intima: possible importance in hemostasis and thrombosis.Nature. 1973;241:217–219.

    Article  CAS  Google Scholar 

  2. Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells.J Clin Invest. 1973;60:914–921.

    Google Scholar 

  3. Sporn LA, Chavin SI, Marder VJ, Wagner DD. Biosynthesis of von Willebrand protein by human megakaryocytes.J Clin Invest. 1985;76:1102–1106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Matsui T, Fujimura Y, Nishida S, Titani K. Human plasma α2- macroglobulin and von Willebrand factor possess covalently linked ABO(H) blood antigens in subjects with corresponding ABO phe- notype.Blood. 1993;82:663–668.

    PubMed  CAS  Google Scholar 

  5. Matsui T, Shimoyama T, Matsumoto M, et al. ABO blood group antigen on human plasma von Willebrand factor after ABO- mismatched bone marrow transplantation.Blood. 1999;94:2895–2900.

    PubMed  CAS  Google Scholar 

  6. Fujimura Y, Titani K. Structure and function of von Willebrand factor. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD, eds.Haemostasis and Thrombosis. New York, NY: Churchill Livingstone; 1994:379–395.

    Google Scholar 

  7. Ruggeri ZM. von Willebrand factor.J Clin Invest. 1997;99:559–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sadler JE. Biochemistry and genetics of von Willebrand factor.Annu Rev Biochem. 1998;67:395–424.

    Article  CAS  PubMed  Google Scholar 

  9. Furlan M. von Willebrand factor: molecular size and functional activity.Ann Hematol. 1996;72:341–348.

    Article  CAS  PubMed  Google Scholar 

  10. Furlan M, Robles R, Lämmle B. Partial purification and characterization of a protease from human plasma cleaving Von Willebrand factor to fragments produced by in vivo proteolysis.Blood. 1996;87:4223–4234.

    PubMed  CAS  Google Scholar 

  11. Tsai H-M. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion.Blood. 1996;87:4235–4244.

    PubMed  CAS  Google Scholar 

  12. Moschcowitz E. Hyaline thrombosis of the terminal arterioles and capillaries; a hitherto undescribed disease.Proc N Y Pathol Soc. 1924;24:21–24.

    Google Scholar 

  13. Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hämolytisch-urämische syndrome: bilaterale Nierenrinden- nekrosen bei akuten erworbenen hämolytischen Anämien.Schweiz Med Wochenschr. 1955;85:905–909.

    PubMed  CAS  Google Scholar 

  14. Furlan M, Robles R, Solenthaler M, Wassmer M, Sandoz P, Lämmle B. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura.Blood. 1997;89:3097–3103.

    PubMed  CAS  Google Scholar 

  15. 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;339:1578–1584.

    Article  CAS  PubMed  Google Scholar 

  16. Tsai H-M, Lian EC-Y. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura.N Engl J Med. 1998;339:1585–1594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Furlan M, Robles R, Solenthaler M, Lämmle B. Acquired deficiency of von Willebrand factor cleaving protease in a patient with thrombotic thrombocytopenic purpura.Blood. 1998;91:2839–2846.

    PubMed  CAS  Google Scholar 

  18. Kinoshita S, Yoshioka A, Park Y-D, et al. Upshaw-Schulman syndrome revisited: a concept of congenital thrombotic thrombocy- topenic purpura.Int J Hematol. 2001;74:101–108.

    Article  CAS  PubMed  Google Scholar 

  19. Hershgold EJ, Sprawls S. Molecular properties of purified human, bovine and porcine antihemophilic globulin (AHG).Fed Proc. 1966;25:317.

    Google Scholar 

  20. Johnson AJ, Newman J, Howell MB, Puszkin S. Purification of anti- hemophilic factor (AHF) for clinical and experimental use.Thromb Diath Haemorrh Suppl. 1967;26:377–381.

    PubMed  CAS  Google Scholar 

  21. Ratnoff OD, Kass L, Lang PD. Studies of the purification of anti- hemophilic factor (factor VIII), II: separation of partially purified antihemophilic factor by gel filtration of plasma.J Clin Invest. 1969;48:957–962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. van Mourik JA, Mochtar IA. Purification of antihemophilic factor (factor VIII) by gel chromatography.Biochim Biophys Acta. 1970;221:677–679.

    Article  CAS  PubMed  Google Scholar 

  23. Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand’s disease. With observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihemophilic factor.J Clin Invest. 1971;50:244–254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Marchesi SL, Shulman NR, Gralnick HR. Studies on the purification and characterization of human factor VIII.J Clin Invest. 1972;51:2151–2161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Legaz ME, Schmer G, Counts RB, Davie EW. Isolation and characterization of human factor VIII (antihemophilic factor).J Biol Chem. 1973;248:3946–3955.

    PubMed  CAS  Google Scholar 

  26. van Mourik JA, Bouma BN, LaBruyère WT, De Graaf S, Mochtar IA. Factor VIII, a series of homologous oligomers and a complex of two proteins.Thromb Res. 1974;4:155–164.

    Article  CAS  PubMed  Google Scholar 

  27. Owen WG, Wagner RH. Antihemophilic factor: separation of an active fragment following dissociation by salts or detergents.Thromb Diath Haemorrh. 1972;27/3:502–515.

    Article  PubMed  CAS  Google Scholar 

  28. Bouma BN, Wiegerink Y, Sixma JJ, van Mourik JA, Mochtar IA. Immunologic characterization of purified antihaemophilic factor A (factor VIII) which corrects abnormal platelet retention in von Willebrand’s disease.Nature. 1972;236:104–106.

    CAS  Google Scholar 

  29. Weiss HJ, Hoyer LW. von Willebrand factor: dissociation from anti- hemophilic factor procoagulant activity.Science. 1973;182:1149–1151.

    Article  CAS  PubMed  Google Scholar 

  30. Cooper HA, Griggs TR, Wagner RH. Factor VIII recombination after dissociation by CaCl2.Proc Natl Acad Sci U S A. 1973;70:2326–2329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rick ME, Hoyer LW. Immunologic studies of antihemophilic factor (AHF, Factor VIII). V. Immunologic properties of AHF sub- units produced by salt dissociation.Blood. 1973;42:737–747.

    PubMed  CAS  Google Scholar 

  32. Meyer D, Jenkins CSO, Dreyfus MD, Fressinaud E, Larrieu M-J. von Willebrand factor and ristocetin, II: relationship between von Willebrand factor, von Willebrand antigen and factor VIII activity.Br J Haematol. 1974;28:579–599.

    Article  CAS  PubMed  Google Scholar 

  33. Hougie C, Seargeant RB, Brown JE, Baugh RF. Evidence that factor VIII and the ristocetin aggregating factor (VIII Rist) are separate molecular entities.Proc Soc Exp Biol Med. 1974;147:58–61.

    Article  CAS  PubMed  Google Scholar 

  34. McKee PA, Andersen JC, Switzer ME. Molecular structural studies of human factor VIII.Ann N Y Acad Sci. 1974;240:8–33.

    Article  Google Scholar 

  35. Toole JJ, Knopf JL, Wozney JM, et al. Molecular cloning of cDNA encoding human antihemophilic factor.Nature. 1984;312:342–347.

    Article  CAS  PubMed  Google Scholar 

  36. Vehar GA, Keyt B, Eaton D, et al. Structure of human factor VIII.Nature. 1984;312:337–342.

    Article  CAS  PubMed  Google Scholar 

  37. Verweij CL, de Vries CJM, Distel B, et al. Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene.Nucleic Acids Res. 1985;13:4699–4717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sadler JE, Shelton-Inlose BB, Sorace JM, Harlan JM, Titani K, Davie EW. Cloning and characterization of two cDNAs coding for human von Willebrand factor.Proc Natl Acad Sci U S A. 1985;82:6394–6398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ginsburg D, Handin RI, Bonthron DT, et al. Human von Wille- brand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosome localization.Science. 1985;228:1401–1406.

    Article  CAS  PubMed  Google Scholar 

  40. Shelton-Inlose BB, Titani K, Sadler JE. cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms.Biochemistry. 1986;25:3164–3171.

    Article  Google Scholar 

  41. Kaufman RJ. Biological regulation of factor VIII activity.Annu Rev Med. 1992;43:325–339.

    Article  CAS  PubMed  Google Scholar 

  42. Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets.J Clin Invest. 1980;65, 1318–1325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ruggeri ZM, Zimmerman TS. The complex multimeric composition of factor VIII/von Willebrand factor.Blood. 1981;57:1140–1143.

    PubMed  CAS  Google Scholar 

  44. Chopek MW, Girma J-P, Fujikawa K, Davie EW, Titani K. Human von Willebrand factor: a multivalent protein composed of identical subunits.Biochemistry. 1986;25:3146–3155.

    Article  CAS  PubMed  Google Scholar 

  45. Girma J-P, Chopek MW, Titani K, Davie EW. Limited proteolysis of human von Willebrand factor byStaphylococcus aureus V-8: isolation and partial characterization of a platelet-binding domain.Biochemistry. 1986;25:3156–3163.

    Article  CAS  PubMed  Google Scholar 

  46. Titani K, Kumar S, Takio K, et al. Amino acid sequence of human von Willebrand factor.Biochemistry. 1986;25:3171–3184.

    Article  CAS  PubMed  Google Scholar 

  47. Wagner DD, Lawrence SO, Ohlsson-Wilheim BM, Fay PJ, Marder VJ. Topology and order of formation of interchain disulfide bonds in von Willebrand factor.Blood. 1987;69:27–32.

    PubMed  CAS  Google Scholar 

  48. Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and factor VIII/ von Willebrand factor in a new subtype of von Willebrand disease.N Engl J Med. 1980;302:1047–1051.

    Article  CAS  PubMed  Google Scholar 

  49. Dent JA, Berkowitz SD, Ware J, Kasper CK, Ruggeri ZM. Identification of a cleavage site directing the immunochemical detection of molecular abnormality in type IIA von Willebrand factor.Proc Natl Acad Sci U S A. 1990;87:6306–6310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothe- lial cells in shear stress-induced platelet aggregation.J Clin Invest. 1986;78:1456–1461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Moake JL, Turner NA, Stathopoulos NA, Nolasco L, Hellums JD. Shear-dependent platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.Blood. 1988;71:1366–1374.

    PubMed  CAS  Google Scholar 

  52. Ikeda Y, Handa M, Kawano K, et al. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.J Clin Invest. 1991;87:1234–1240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Alevriadou BR, Moake JL, Turner NA, et al. Real-time analysis of shear-dependent thrombus formation and its blockade by inhibitors of von Willebrand factor binding to platelets.Blood. 1993;81:1263–1276.

    PubMed  CAS  Google Scholar 

  54. Siedlecki CA, Lestini BJ, Kottke-Marchant K, Eppell SJ, Wilson DL. Shear-dependent changes in the 3-dimensional structure of human von Willebrand factor.Blood. 1996;88:2939–2950.

    PubMed  CAS  Google Scholar 

  55. Tsai H-M, Sussman II, Nagel RL. Shear stress enhances the prote- olysis of von Willebrand factor in normal plasma.Blood. 1994;83:2171–2179.

    PubMed  CAS  Google Scholar 

  56. Gerritsen HE, Turecek PL, Schwarz HP, Lämmle B, 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;82:1386–1389.

    Article  CAS  PubMed  Google Scholar 

  57. Obert B, Tout H, Veyradier A, Fressinaud E, Meyer D, Girma J-P. Estimation of the von Willebrand factor-cleaving protease in plasma using monoclonal antibodies to vWF.Thromb Haemost. 1999;82:1382–1385.

    Article  CAS  PubMed  Google Scholar 

  58. Kasper CK, Aledort LM, Counts RB, et al. A more uniform measurement of factor VIII inhibitors.Thromb Diath Haemorrh. 1975;34:869–872.

    Google Scholar 

  59. Ashida A, Nakakura H, Matsumoto M, et al. An infant of TTP with a high titer inhibitor to von Willebrand factor-cleaving protease activity [abstract].Acta Paediatr Jap. 2001;105:293.

    Google Scholar 

  60. Tsai HM, Li A, Rock G. Inhibitors of von Willebrand factor- cleaving protease in thrombotic thrombocytopenic purpura.Clin Lab. 2001;46:387–392.

    Google Scholar 

  61. Tsai H-M. High titers of inhibitor of von Willebrand factor-cleaving metalloproteinase in a fatal case of acute thrombotic thrombo-cytopenic purpura.Am J Hematol. 2001;65:251–255.

    Article  Google Scholar 

  62. Bell WR. Thrombotic thrombocytopenic purpura/hemolytic ure- mic syndrome relapse: frequency, pathogenesis, and meaning.Semin Hematol. 1997;34:134–139.

    PubMed  CAS  Google Scholar 

  63. Kakishita E. Pathophysiology and treatment of thrombotic throm- bocytopenic purpura/hemolytic uremic syndrome (TTP/HUS).Int J Hematol. 2000;71:320–327.

    PubMed  CAS  Google Scholar 

  64. Cines DB, Konkle BA, Furlan M. Thrombotic thrombocytopenic purpura: a paradigm shift?Thromb Haemost. 2000;84:528–535.

    Article  CAS  PubMed  Google Scholar 

  65. Yagi H, Narita N, Matsumoto N, et al. Enhanced low shear stress induced platelet aggregation by Shiga-like toxin 1 purified from Escherichia coli O157.Am J Hematol. 2001;66:105–115.

    Article  CAS  PubMed  Google Scholar 

  66. van der Plas RM, Schiphorst ME, Huizinga EG, et al. von Wille- brand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura.Blood. 1999;93:3798–3802.

    PubMed  CAS  Google Scholar 

  67. Canciani MT, Forza I, Lattuada A, Rossi E, Mannucci PM. von Willebrand factor(VWF) cleaving protease in health and disease [abstract].Thromb Haemost Suppl. 2001. Abstract 1668.

  68. Takahashi Y, Kawaguchi C, Hanesaka Y, Fujimura Y, Yoshioka A. Plasmavon Willebrand factor-cleaving protease is low in the new- borns.Thromb Haemost Suppl. 2001;Abs 285.

  69. Raife TJ, Atkinson BS, Montgomery RR. Comparative von Willebrand factor cleaving proteolytic activity in human saliva, serum and plasma [abstract].Blood. 2000;96:2705.

    Google Scholar 

  70. Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human vWF-cleaving protease and its identification as a new member of the metalloproteinase family.Blood. 2001;98:1662–1666.

    Article  CAS  PubMed  Google Scholar 

  71. Wolfsberg TG, Straight PD, Gerena RL, et al. ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain.Develop Biol. 1995;169:378–383.

    Article  CAS  PubMed  Google Scholar 

  72. Gerritsen H, Robles R, Lämmle B, Furlan M. Partial amino acid sequence of purified von Willebrand factor-cleaving protease.Blood. 2001;98:1654–1661.

    Article  CAS  PubMed  Google Scholar 

  73. Matsumoto M, Chisuwa H, Nakazawa Y, et al. Living-related liver transplantation rescues reduced vWF-cleaving protease activity in patients with cirrhotic biliary atresia [abstract].Blood. 2000;96:636a.

    Google Scholar 

  74. Zheng X, Chung D, Takayama TH, Majerus EM, Sadler JE, Fujikawa K. Structure of von Willebrand factor cleaving protease (ADMTS13), a metalloprotease involved in thrombotic thrombo- cytopenic purpura.J Biol Chem. 2001;276:41059–41063.

    Article  CAS  PubMed  Google Scholar 

  75. Soejima K, Mimura N, Hirashima M, et al. A novel human metal- loprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease?J Biochem. 2001;130:475–480.

    Article  CAS  PubMed  Google Scholar 

  76. Dacie JV, Mollison PL, Richardson N, Selwyn JG, Shapiro L. Atyp- ical congenital haemolytic anaemia.Q J Med. 1953;85:79–98.

    Google Scholar 

  77. Monnens LAH, Retera RJM. Thrombotic thrombocytopenic purpura in a neonatal infant.J Pediatr. 1967;71:118–123.

    Article  CAS  PubMed  Google Scholar 

  78. Wallace DC, Lovric A, Clubb JS, Carseldine DB. Thrombotic throm- bocytopenic purpura in four siblings.Am J Med. 1975;58:724–734.

    Article  CAS  PubMed  Google Scholar 

  79. Schulman I, Pierce M, Likens A, Currimbhoy Z. Studies on throm- bopoiesis, I: a factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency.Blood. 1960;14:943–957.

    Google Scholar 

  80. Upshaw JD. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia.N Engl J Med. 1978;298:1350–1352.

    Article  PubMed  Google Scholar 

  81. Rennard S, Abe S. Decreased cold-insoluble globulin in congenital thrombocytopenia (Upshaw-Schulman syndrome).N Engl J Med. 1979;300:368.

    PubMed  CAS  Google Scholar 

  82. Koizumi S, Miura M, Yamagami M, Horita N, Taniguchi N, Migita S. Upshaw-Schulman syndrome and fibronectin (cold-insoluble globulin).N Engl J Med. 1981;305:1284–1285.

    PubMed  CAS  Google Scholar 

  83. Goodnough LT, Saito H, Ratnoff OD. Fibronectin levels in congenital thrombocytopenia: Schulman’s syndrome.N Engl J Med. 1982;306:938–939.

    Article  CAS  PubMed  Google Scholar 

  84. Shinohara T, Miyamura S, Suzuki E, Kobayashi K. Congenital microangiopathic hemolytic anemia: report of a Japanese girl.Eur J Pediatr. 1982;138:191–193.

    Article  CAS  PubMed  Google Scholar 

  85. Moake JL, Rudy C K, Troll J H, et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura.N Engl J Med. 1982;307:1432–1435.

    Article  CAS  PubMed  Google Scholar 

  86. Moake JL, Byrnes JJ, Troll JH, et al. Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multi- meric forms in chronic relapsing thrombotic thrombocytopenic purpura.Blood. 1985;65:1232–1236.

    PubMed  CAS  Google Scholar 

  87. Miura M, Koizumi S, Nakamura K, et al. Efficiency of several plasma components in a young boy with chronic thrombocytopenia and hemolytic anemia who responds repeatedly to normal plasma infusions.Am J Hematol. 1984;17:307–319.

    Article  CAS  PubMed  Google Scholar 

  88. Hara T, Kitano A, Kajiwara T, Kondo T, Sakai K, Hamasaki Y. Factor VIII concentrate-responsive thrombocytopenia, hemolytic anemia, and nephropathy. Evidence that factor VIII:von Willebrand factor is involved in its pathogenesis.Am J Ped Hematol Oncol. 1986;8:324–328.

    Article  CAS  Google Scholar 

  89. Karpman D, Holmberg L, Jirgard L, Lethagen S. Increased platelet retention in familial recurrent thrombotic thrombocytopenic purpura.Kidney Int. 1996;49:190–199.

    Article  CAS  PubMed  Google Scholar 

  90. Miura M, Koizumi S, Miyazaki H. Thrombopoietin in Upshaw- Schulman syndrome.Blood. 1997;89:4663–4664.

    PubMed  CAS  Google Scholar 

  91. Yagi H, Konno M, Kinoshita S, et al. Plasma of patients with Upshaw-Schulman syndrome, a congenital deficiency of von Wille- brand factor-cleaving protease, enhances the aggregation of normal platelets under high shear stress.Br J Haematol. 2001;115:991–997.

    Article  CAS  PubMed  Google Scholar 

  92. Moake JL, Turner NA, Stathopoulas NA, Nolasco L, Hellums JD. Shear-induced platelet aggregation can be mediated by vWF release from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and its resistant to aspirin.Blood. 1988;71:1366–1374.

    PubMed  CAS  Google Scholar 

  93. Chow TW, Hellums JD, Moake JL, Kroll M. Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation.Blood. 1992;80:113–120.

    PubMed  CAS  Google Scholar 

  94. Makita K, Shimoyama T, Sakurai Y, et al. Placental ecto-ATP diphosphohydrolase: its structural feature distinct from CD39, localization and inhibition on shear-induced platelet aggregation.Int J Hematol. 1998;68:297–310.

    Article  CAS  PubMed  Google Scholar 

  95. Gachet C. ADP receptors of platelets and their inhibition.Thromb Haemost. 2001;86:222–232.

    Article  CAS  PubMed  Google Scholar 

  96. Feldman JD, Mardiney MR, Uranue ER, Cutting H. The vascular pathology of thrombotic thrombocytopenic purpura. An immuno- histochemical and ultrastructural study.Lab Invest. 1966;15:927–946.

    PubMed  CAS  Google Scholar 

  97. Neame PB, Lechago J, Ling ET, Koval A. Thrombotic thrombocy- topenic purpura: report of a case with disseminated intravascular platelet aggregation.Blood. 1973;42:805–814.

    PubMed  CAS  Google Scholar 

  98. Asada Y, Sumiyoshi A, Hayashi T, Suzumiya J, Kaketani K. Immunohistochemistry of vascular lesion in thrombotic thrombo- cytopenic purpura, with special reference to factor VIII related antigen.Thromb Res. 1985;38:469–479.

    Article  CAS  PubMed  Google Scholar 

  99. Bull BS, Kuhn IH. The production of schistocytes by fibrin strands (a scanning electron microscope study).Blood. 1970;35:104–111.

    PubMed  CAS  Google Scholar 

  100. Konno M, Yoshioka A, Takase T, Imai T. Partial clinical improvement in Upshaw-Schulman syndrome following prostacyclin infusion.Acta Paediat Jap. 1995;37:97–100.

    Article  CAS  Google Scholar 

  101. Xie L, Chesterman CN, Hogg PJ. Reduction of von Willebrand factor by endothelial cells.Thromb Haemost. 2000;84:506–513.

    Article  CAS  PubMed  Google Scholar 

  102. Xie L, Dai CN, Chesterman CN, Hogg PJ. Thrombospondin-1 controls thehaemostatic activity of von Willebrand factor.Thromb Haemost. 2001;Abs OC85.

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Authors and Affiliations

  1. Department of Blood Transfusion Medicine, Fujita Health University, Aichi, Japan

    Yoshihiro Fujimura & Masanori Matsumoto

  2. Second Department of Internal Medicine, Fujita Health University, Aichi, Japan

    Hideo Yagi

  3. Department of Pediatrics, Nara Medical University, Nara, Japan

    Akira Yoshioka

  4. Institute for Comprehensive Medical Science, Fujita Health University, Aichi, Japan

    Taei Matsui & Koiti Titani

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  1. Yoshihiro Fujimura
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  2. Masanori Matsumoto
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  3. Hideo Yagi
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  6. Koiti Titani
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Correspondence to Yoshihiro Fujimura.

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Fujimura, Y., Matsumoto, M., Yagi, H. et al. von Willebrand Factor—Cleaving Protease and Upshaw-Schulman Syndrome. Int J Hematol 75, 25–34 (2002). https://doi.org/10.1007/BF02981975

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