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Thromb Haemost 1997; 78(06): 1456-1462
DOI: 10.1055/s-0038-1665433
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Schattauer GmbH Stuttgart

von Willebrand Factor Mediates Increased Platelet Retention in Recurrent Thrombotic Thrombocytopenic Purpura

Diana Karpman
1   The Department of Pediatrics, University of Lund, Sweden
,
Stefan Lethagen
2   Department of Coagulation Disorders, University Hospital, Malmö, Sweden
,
AnnCharlotte Kristoffersson
1   The Department of Pediatrics, University of Lund, Sweden
,
Christina Isaksson
1   The Department of Pediatrics, University of Lund, Sweden
,
Lars Holmberg
1   The Department of Pediatrics, University of Lund, Sweden
› Author Affiliations
Further Information

Publication History

Received 25 1997

Accepted after resubmission 04 August 1997

Publication Date:
12 July 2018 (online)

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Summary

The plasma cryoprecipitate of two brothers with recurrent thrombotic thrombocytopenic purpura (TTP) was previously found to mediate increased platelet retention and contain ultra-large von Willebrand factor (vWF) multimers during remissions. We conducted this study to examine if vWF is involved in the increased platelet retention in TTP. Platelet retention decreased when the patients’ plasma was incubated with a monoclonal antibody directed to the vWF epitope which interacts with the platelet receptor glycoprotein Ib or when incubated with a Fab-fragment directed to the platelet receptor glycoprotein IIb/IIIa. Replacement of patient vWF with an equivalent concentration of a factor VIII/vWF concentrate containing no ultra-large vWF multimers was accompanied by a normalization of platelet retention. These results indicate that vWF is involved in the increased platelet retention. Analysis of polymorphic markers in the vWF gene demonstrated that a recessive mutation in this gene is unlikely.

 

  • References

  • 1 Moake JL. Thrombotic thrombocytopenic purpura. Thromb Haemost 1995; 74: 240-245
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Asada Y, Sumiyoshi A, Hayashi T, Suzumiya J, Kaketani K. Immunohisto-chemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen. Thromb Res 1985; 38: 469-479
    CrossrefPubMedGoogle Scholar
  • 3 Aster RH. Plasma therapy for thrombotic thrombocytopenic purpura. N Engl J Med 1985; 312: 985-987
    CrossrefPubMedGoogle Scholar
  • 4 Roth GJ. Platelets and blood vessels: the adhesion event. Immun Today 1992; 13: 100-105
    CrossrefPubMedGoogle Scholar
  • 5 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Heliums JD. 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 1986; 78: 1456-1461
    CrossrefPubMedGoogle Scholar
  • 6 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggeri ZM. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234-1240
    CrossrefPubMedGoogle Scholar
  • 7 Goto S, Salomon DR, Ikeda Y, Ruggeri ZM. Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Willebrand factor to platelets. J Biol Chem 1995; 270: 23352-23361
    CrossrefPubMedGoogle Scholar
  • 8 Moake J, Chintagumpala M, Turner N, McPherson P, Nolasco L, Steuber C, Santiago-Borrero P, Horowitz M, Pehta J. Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura. Blood 1994; 84: 490-497
    PubMedGoogle Scholar
  • 9 Karpman D, Holmberg L, Jirgård L, Lethagen S. Increased platelet retention in familial recurrent thrombotic thrombocytopenic purpura. Kidney Int 1996; 49: 190-199
    CrossrefPubMedGoogle Scholar
  • 10 Siddiqui FA, Lian ECY. Novel platelet agglutinating protein from a thrombotic thrombocytopenic purpura plasma. J Clin Invest 1985; 76: 1330-1337
    CrossrefPubMedGoogle Scholar
  • 11 Kelton JC, Moore J, Santos A, Sheridan D. Detection of a platelet agglutinating factor in thrombotic thrombocytopenic purpura. Ann Intern Med 1984; 101: 589-593
    CrossrefPubMedGoogle Scholar
  • 12 Frangos JA, Moake JL, Nolasco L, Phillips MD, Mclntire LV. Cryosuper-natant regulates accumulation of unusually large vWF multimers from endothelial cells. Am J Physiol 1989; 256: H1635-H144
    PubMedGoogle Scholar
  • 13 Girina JP, Fressinaud E, Christophe O, Rouault C, Obert B, Takayashi Y, Meyer D. Aurin tricarboxylic acid inhibits platelet adhesion to collagen by binding to the 509-695 disulphide loop of von Willebrand factor and competing with glycoprotein lb. Thromb Haemost 1992; 68: 707-713
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Coller BS. A new murine monoclonal antibody reports an activation-dependent change in conformation and/or microenvironment of the platelet glycoprotein Ilb/IIIa complex. J Clin Invest 1985; 76: 101-108
    CrossrefPubMedGoogle Scholar
  • 15 Ruan C, Tobelem G, McMichael AJ, Drouet L, Legrand Y, Degos L, Kieffer N, Lee H, Caen JP. Monoclonal antibody to human platelet glycoprotein I. Br J Haematol 1981; 49: 511-519
    CrossrefPubMedGoogle Scholar
  • 16 Lethagen S, Nilsson IM. DDAVP induced enhancement of platelet retention. Its dependence on platelet – von Willebrand factor and the platelet receptor GPIIb/IIIa. Eur J Haematol 1992; 49: 07-13
    PubMedGoogle Scholar
  • 17 Johansson BG. Agarose gel electrophoresis. Scand J Clin Invest 1972; (Suppl. 029) 124: 07-19
    PubMedGoogle Scholar
  • 18 Lethagen S, Bemtorp E, Nilsson IM. Pharmacokinetics and hemostatic effect of different factor VUI/von Willebrand factor concentrates in von Willebrand’s disease type III. Ann Hematol 1992; 65: 253-259
    CrossrefPubMedGoogle Scholar
  • 19 Ruggeri ZM, Zimmerman TS. The complex multimeric composition of factor VUI/von Willebrand factor. Blood 1981; 57: 1140-1143
    PubMedGoogle Scholar
  • 20 Wüst T, Beeser H, Lang HR. Influence of different surfactants on the separation of von Willebrand multimers by use of agarose gel electrophoresis and semi dry blotting technology. Thromb Res 1991; 61: 181-189
    CrossrefPubMedGoogle Scholar
  • 21 Blin N, Stafford DW. A general method for isolation of high molecular weight DNA from eukarocytes. Nucl Acid Res 1976; 3: 2303-2308
    CrossrefPubMedGoogle Scholar
  • 22 Zhang ZP, Blombäck M, Egberg N, Falk G, Anvret M. Characterization of the von Willebrand factor gene (vWF) in von Willebrand Disease type III patients from 24 families of Swedish and Finnish origin. Genomics 1994; 21: 188-193
    CrossrefPubMedGoogle Scholar
  • 23 Mancuso DJ, Tuley EA, Westfield LA, Lester-Mancuso TL, Le Beau MM, Sorace JM, Sadler JE. Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction. Biochemistry 1991; 30: 253-269
    CrossrefPubMedGoogle Scholar
  • 24 Donnér M, Holmberg L, Kristoffersson A-C, Nilsson IM. An Hphl-polymorphism in exon 28 of the von Willebrand factor gene, and its frequency among patients with various forms of von Willebrand disease. Br J Haematol 1991; 78: 403-407
    CrossrefPubMedGoogle Scholar
  • 25 Peake IR, Bowen D, Bignell P, Liddell MB, Sadler JE, Standen G, Bloom AL. Family studies and prenatal diagnosis in severe von Willebrand disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene. Blood 1990; 76: 555-561
    PubMedGoogle Scholar
  • 26 Nichols WC, Lyons SE, Harrison JS, Cody RL, Ginsburg D. Severe von Willebrand disease due to a defect at the level of von Willebrand factor mRNA expression: detection by exonic PCR-restriction fragment length polymorphism analysis. Proc Natl Acad Sci USA 1991; 88: 3857-3861
    CrossrefPubMedGoogle Scholar
  • 27 Mancuso DJ, Tuley EA, Westfield LA, Worrall NK, Shelton-Inloes BB, Sorace JM, Alevy YG, Sadler JE. Structure of the gene for human von Willebrand factor. J Biol Chem 1989; 264: 19514-19527
    PubMedGoogle Scholar
  • 28 Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, Seder RH, Hong SL, Deykin D. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 1982; 307: 1432-1435
    CrossrefPubMedGoogle Scholar
  • 29 Moake JL, Brynes JJ, Troll JH, Rudy CK, Hong SL, Weinstein MJ, Colannino NM. Effects of fresh frozen plasma and its cryosupematant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura. Blood 1985; 65: 1232-1236
    PubMedGoogle Scholar
  • 30 Phillips MD, Moake JL, Nolasco L, Turner N. Aurin tricarboxylic acid: a novel inhibitor of the association of von Willebrand factor and platelets. Blood 1988; 72: 1898-1903
    PubMedGoogle Scholar
  • 31 Hellem AJ. Platelet adhesiveness in von Willebrand’s disease. A study with a new modification of the glass bead filter method. Scand J Haematol 1970; 7: 374-382
    PubMedGoogle Scholar
  • 32 Salzman EW. Measurement of platelet adhesiveness: a simple in vitro technique demonstrating an abnormality in von Willebrand’s disease. J Lab Clin Med 1963; 62: 724-735
    PubMedGoogle Scholar
  • 33 Zoja C, Remuzzi G. Role of platelets in progressive glomerular diseases. Pediatr Nephrol 1995; 9: 495-502
    CrossrefPubMedGoogle Scholar
  • 34 Thiagarajan P, Kelly KL. Exposure of binding sites for vitronectin on platelets following stimulation. J Biol Chem 1988; 263: 3035-3038
    PubMedGoogle Scholar
  • 35 Kroll MH, Heliums JD, Mclntire LV, Schafer Al, Moake JL. Platelets and shear stress. Blood 1996; 88: 1525-1541
    CrossrefPubMedGoogle Scholar
  • 36 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
    CrossrefPubMedGoogle Scholar