Download PDF
Thromb Haemost 1979; 42(03): 1033-1038
DOI: 10.1055/s-0038-1656994
Original Article
Schattauer GmbH Stuttgart

VIIIR: Ag in Platelets from Patients with Various Forms of von Willebrand’s Disease

L Holmbeg
The Department of Paediatrics and the Coagulation Laboratory, Allmdnna Sjukhuset, University of Lund, Malmö, Sweden
,
Inga Marie Nilsson
The Department of Paediatrics and the Coagulation Laboratory, Allmdnna Sjukhuset, University of Lund, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

Received 03 January 1979

Accepted 04 April 1979

Publication Date:
23 August 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Thirty patients with various forms of von Willebrand’s disease were investigated for VIIIR: Ag in their platelets. VIIIR: Ag was extracted from washed platelets and measured both with electroimmunoassay and a sensitive immunoradiometric assay. Six patients had severe von Willebrand’s disease, type I, with very low or no VIIIR: Ag in their plasma. None of these patients had any VIIIR: Ag detectable in their platelets. All 19 patients with mild von Willebrand’s disease had VIIIR: Ag in their platelets but the values often fell below those of normal controls. Five patients with genetic variants of von Willebrand’s disease also had values in their platelets corresponding to those in plasma.

Von Willebrand’s disease is a bleeding disorder caused by an inherited defect in so-called factor VIII related antigen (VIIIR: Ag), which is a protein normally occurring in plasma (Zimmerman et al. 1971), endothelial cells (Bloom et al. 1973), platelets (Howard et al. 1974) and megakaryocytes (Piovella et al. 1974). The defect leads to a prolonged bleeding time and as a rule a secondary decrease in factor VIII clotting activity (VIII: C) in plasma. Von Willebrand’s disease is a heterogeneous condition (Holmberg and Nilsson 1972). It varies widely in severity, and a genetic variation causing a qualitative abnormality of VIIIR :Ag is also known (Peake et al. 1974). The disease is, as a rule, transmitted as an autosomal and dominant trait, but some severely affected individuals have been suspected to be homozygous for an autosomal and more or less recessive gene (Italian Working Group 1977, Shoa’i et al. 1977).

The clinical severity of the disease varies with the amount of functional VIIIR :Ag (VIIIR: RCF) in plasma (Holmberg and Nilsson 1972, Meyer et al. 1974). Patients with severe von Willebrand’s disease have very little or no VIIIR: Ag in their plasma. They also lack the protein in their endothelial cells (Holmberg et al. 1974 b). There is evidence that also their platelets are devoid of VIIIR :Ag. In the present investigation we studied the platelet content of VIIIR: Ag in a series of patients with various types of von Willebrand’s disease. Both electroimmunoassay (EIA) and a more sensitive immunoradiometric assay (IRMA) for VIIIR: Ag were used.

 

  • References

  • 1 Bloom AL, Giddings JC, Wilks CJ. 1973; Factor VIII on the vascular intima: possible importance in haemostasis and thrombosis. Nature New Biology 241: 217
    CrossrefPubMedGoogle Scholar
  • 2 Bouma BN, Horduk-Hos JM, De Graaf S, Skma JJ, Van Mourik JA. 1975; Presence of factor VIII-related antigen in blood platelets of patients with von Willebrand’s disease. Nature 257: 510
    CrossrefPubMedGoogle Scholar
  • 3 Coller BS, Hirschman J, Gralnick HR. 1975; Studies on factor VIII/von Willebrand factor antigen on human platelets. Thrombosis Research 6: 469
    CrossrefPubMedGoogle Scholar
  • 4 Cronberg S, Kubisz P, Caen J. 1970; Demonstration of a plasmatic cofactor different from fibrinogen necessary for platelet release by ADP and adrenaline. Thrombosis et Diathesis Haemorrhagica 24: 409
    PubMedGoogle Scholar
  • 5 Green D, Potter EV. 1976; Platelet-bound ristocetin aggregation factor in normal subjects and patients with von Willebrand’s disease. Journal of Laboratory and Clinical Medicine 87: 976
    PubMedGoogle Scholar
  • 6 Holmberg L, Ljung R. 1978; Purification of F VIII :C by antigen-antibody chromatography. Thrombosis Research 12: 667
    CrossrefPubMedGoogle Scholar
  • 7 Holmberg L, Mannucci PM, Nilsson IM. 1974. a Vascular factor VIII in von Willebrand’s disease. Excerpta Medica International Congress Series No. 356 Haemophilia. Excerpta Medica; Amsterdam: p 133
    Google Scholar
  • 8 Holmberg L, Mannucci PM, Turesson I, Ruggeri ZM, Nilsson IM. 1974; a Factor VIII antigen in the vessel walls in von Willebrand’s disease and haemophilia A. Scandinavian Journal of Haematology 13: 33
    PubMedGoogle Scholar
  • 9 Holmberg L, Nillson IM. 1972; Genetic variants of von Willebrand’s disease. British Medical Journal 2: 317
    PubMedGoogle Scholar
  • 10 Howard MA, Montgomery DC, Hardisty RM. 1974; Factor VIII related antigen in platelets. Thrombosis Research 4: 611
    PubMedGoogle Scholar
  • 11 Hoyer LW, De Los Santos RP, Hoyer JR. 1973; Antihemophilic factor antigen. Localization in endothelial cells by immunofluorescent microscopy Journal of Clinical Investigation 52: 2737
    CrossrefPubMedGoogle Scholar
  • 12 Italian Working Group. 1977; Spectrum of von Willebrand’s disease: a study of 100 cases. British Journal of Haematology 35: 101
    CrossrefPubMedGoogle Scholar
  • 13 Jaffe E. 1977; Endothelial cells and the biology of factor VIII. New England Journal of Medicine 296: 377
    CrossrefPubMedGoogle Scholar
  • 14 Jaffe EA, Hoyer LW, Nachman RL. 1973; Synthesis of antihemophilic factor antigen by cultured human endothelial cells. Journal of Clinical Investigation 52: 2757
    CrossrefPubMedGoogle Scholar
  • 15 Mannucci PM, Pareti FI, Holmberg L, Nilsson IM, Ruggeri ZM. 1976; Studies on the prolonged bleeding time in von Willebrand’s disease. Journal of Laboratory and Clinical Medicine 88: 662
    PubMedGoogle Scholar
  • 16 Meyer D, Jenkins CS P, Dreyfus MD, Fressinaud E, Larrieu M-J. 1974; Willebrand factor and ristocetin. II. Relationship between Willebrand factor, Willebrand antigen and factor VIII activity. British Journal of Haematology 28: 579
    CrossrefPubMedGoogle Scholar
  • 17 Nachman RL, Jaffe EA. 1975; Subcellular platelet factor VIII antigen and von Willebrand factor. Journal of Experimental Medicine 141: 1101
    CrossrefPubMedGoogle Scholar
  • 18 Nachman R, Levine R, Jaffe EA. 1977; Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. Journal of Clinical Investigation 60: 914
    CrossrefPubMedGoogle Scholar
  • 19 Nilsson IM. 1978; Report of the working party on factor VIII related antigens. Thrombosis and Haemostasis 39: 511
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Peake IR, Bloom AL, Giddings JC. 1974; Inherited variants of factor VIII related protein in von Willebrand’s disease. New England Journal of Medicine 291: 113
    CrossrefPubMedGoogle Scholar
  • 21 Piovella F, Ascari E, Sitar GM, Malamani GD, Cattaneo G, Magliulo E, Storti E. 1974; Immunofluorescent detection of factor VIII related antigen in human platelets and megakaryocytes. Haemostasis 3: 288
    PubMedGoogle Scholar
  • 22 Piovella F, Nalli G, Malamani GD, Majolino I, Frassoni G, Sitar GM, Ruggeri A, Dell’orbo C, Ascari E. 1978; The ultrastructural localization of factor VIII-antigen in human platelets, megakaryocytes and endothelial cells utilizing a ferritin-labelled antibody. British Journal of Haematology 39: 209
    CrossrefPubMedGoogle Scholar
  • 23 Ruggeri ZM, Mannucci PM, Bader R, Barbui T. 1978; Factor VIII related properties in platelets from patients with von Willebrand’s disease. Journal of Laboratory and Clinical Medicine 91: 132
    PubMedGoogle Scholar
  • 24 Shoa’i I, Lavergne JM, Ardaillou N, Obert B, Ala F, Meyer D. 1977; Heterogeneity of von Willebrand’s disease: study of 40 Iranian cases. British Journal of Haematology 37: 67
    CrossrefPubMedGoogle Scholar
  • 25 Sultan Y, Bouma BN, De Graaf S, Simeon J, Caen JP, Sdcma JJ. 1977; Factor VIII related antigen in platelets of patients with von Willebrand’s disease. Thrombosis Research 11: 23
    CrossrefPubMedGoogle Scholar
  • 26 Sultan Y, Jeanneau C, Lamaziere J, Maisonneuve P, Caen JP. 1978; Platelet factor VIII related antigen: studies in vivo after transfusion in patients with von Willebrand disease. Blood 51: 751
    PubMedGoogle Scholar
  • 27 Zimmerman TS, Ratnoff OD, Powell AE. 1971; Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand’s disease. Journal of Clinical Investigation 50: 244
    CrossrefPubMedGoogle Scholar
  • 28 Zuzel M, Nilsson IM, Aberg M. 1978; A method for measuring plasma ristocetin cofactor activity. Thrombosis Research 12: 745
    CrossrefPubMedGoogle Scholar