Download PDF
Thromb Haemost 1983; 50(04): 864-868
DOI: 10.1055/s-0038-1665330
Original Article
Schattauer GmbH Stuttgart

Differences Between Heterozygous Dominant and Recessive von Willebrand’s Disease Type I Expressed by Bleeding Symptoms and Combinations of Factor VIII Variables

T B Wahlberg
The Dept of Blood Coagulation Disorders, Karolinska Hospital, Stockholm, Sweden
,
M Blombäck
The Dept of Blood Coagulation Disorders, Karolinska Hospital, Stockholm, Sweden
,
Z M Ruggeri
1   The Depts of Immunology and of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California, U.S.A.
› Author Affiliations
Further Information

Publication History

Received 21 January 1983

Accepted 10 October 1983

Publication Date:
18 July 2018 (online)

Also available at
 PDF Download  Permissions and Reprints

Summary

Three families with von Willebrand’s disease (vWd) type I were investigated. A reliable identification of healthy and diseased individuals was achieved by number of bleeding symptoms, assays of bleeding time, FVIII:C (one stage and two stage), VIIIR: Ag (EIA) and ristocetin cofactor. The diagnoses - vWd or non-vWd were confirmed by laboratory indices based on predictive values of positive and negative tests, also including VIIIR: Ag (IRMA and RIA). The last mentioned two variables did not contribute to significantly better identification of vWd versus health. The best single test variable for this purpose was ristocetin cofactor. One vWd family had significantly higher levels of ristocetin cofactor and shorter bleeding time than the other two vWd families and is probably the typical example of a family transmitting classical severe vWd.

Keywords

Bleeding time - Factor VIII - Bleeding symptoms - Ristocetin cofactor - Predictive values - Diagnostic index - von Wille-brand’s disease
 

  • References

  • 1 Hoyer LW. The factor VIII complex: Structure and function. Blood 1981; 58: 1-13
    PubMedSearch in Google Scholar
  • 2 European Thrombosis Research Organization (ETRO) working party on factor VIII related activities and working party on variants of von Willebrand’s disease. malmö, sweden: Feb 9-10, 1981
  • 3 Zimmerman TS, Ruggeri ZM. Von Willebrand’s disease. Clin Haematol 1983; 12: 175-200
    PubMedSearch in Google Scholar
  • 4 Nilsson IM, Vilhardt H, Holmberg L, Åstedt B. Association between factor VIII related antigen and plasminogen activator. Acta Med Scand 1982; 211: 105-112
    PubMedSearch in Google Scholar
  • 5 Sultan J, Simeon J, Caen JP. Detection of heterozygotes in both parents of homozygous patients with von Willebrand’s disease. J Clin Pathol 1975; 28: 309-316
    CrossrefPubMedSearch in Google Scholar
  • 6 Zimmerman TS, Abildgaard CF, Meyer D. The factor VIII abnormality in severe von Willebrand’s disease. N Engl J Med 1979; 301: 1307-1310
    CrossrefPubMedSearch in Google Scholar
  • 7 Ruggeri ZM, Zimmerman TS. Classification of variant von Wille-brand’s disease subtypes by analysis of functional characteristics and multimeric composition of factor VIII/von Willebrand factor. Ann N Y Acad Sci 1981; 370: 205-209
    CrossrefPubMedSearch in Google Scholar
  • 8 Wahlberg T, Savidge G, Blombäck M, Wiechel B. Influence of age, sex and blood groups on 15 blood coagulation laboratory variables in a reference material composed of 80 blood donors. Vox Sang 1980; 39: 301-308
    CrossrefPubMedSearch in Google Scholar
  • 9 Wahlberg T. Carriers and non-carriers of haemophilia A: Multivariate analysis of pedigree data, blood coagulation variables and bleeding symptoms. Thesis, Karolinska Institute; Stockholm: 1981
    Search in Google Scholar
  • 10 Nilsson IM, Magnusson S, Borchgrevink C. The Duke and Ivy methods for determination of the bleeding time. Thrombos Diathes Haemorrh 1963; 10: 223-234
    PubMedSearch in Google Scholar
  • 11 Nilsson IM, Blombäck M, Thilen A, von Francken I. Carriers of haemophilia A. Acta Med Scand 1959; 165: 357-370
    PubMedSearch in Google Scholar
  • 12 Savidge GF, Blombäck M, Blombäck B. Studies of F VIII procoagu-lant activity in plasma and concentrates using a semiautomated thrombin generation assay. Thromb Res 1979; 16: 355-365
    CrossrefPubMedSearch in Google Scholar
  • 13 Zimmerman TS, Ratnoff OD, Powell AE. Immunological differ-entiation of classic hemophilia (factor VIII deficiency) and von Willebrand’s disease. J Clin Invest 1971; 50: 244-254
    CrossrefPubMedSearch in Google Scholar
  • 14 Savidge GF, Carlebjörk G. An optimized radioimmunoassay of F VUI-related antigen (F VIII: Ag) in plasma and eluates. Thromb Res 1979; 14: 363-376
    CrossrefPubMedSearch in Google Scholar
  • 15 Hoyer LW. Immunologic studies of antihemophilic factor (AHF; factor VIII). IV Radioimmunoassay of AHF antigen. J Lab Clin Med 1972; 80: 822-833
    PubMedSearch in Google Scholar
  • 16 Stibbe J, Kirby EP. The influence of haemaccel fibrinogen and albumin on ristocetin-induced platelet aggregation. Relevance to the quantitative measurement of the ristocetin cofactor Thromb Res 1976; 8: 151-165
    CrossrefPubMedSearch in Google Scholar
  • 17 Bowman RP, Head DR, Marmer DJ, Broissot TD. Improved von Willebrand’s assay using ristocetin with standardized fixed-frozen platelets. Abstract 19th Annual Meeting of Am Soc Hematol; Boston: 1976
    Search in Google Scholar
  • 18 Wahlberg T, Blombäck M. Improved detection of haemophilia A carriers by factor VIII related antigen (radioimmunoassay) and bleeding symptoms. Thromb Res 1981; 21: 339-346
    CrossrefPubMedSearch in Google Scholar
  • 19 Hall P. Periodic health evaluation of individuals. In: Wagner G, Reichertz PL, Masè E. (Eds) Technology and Health: Man and his world. Lecture notes in medical informatics. Vol 7 pp 25-41 Springer; Berlin, Heidelberg, New York: 1980
    Search in Google Scholar
  • 20 Wahlberg T, Blombäck M, Hall P, Axelsson G. Application of indicators predictors and diagnostic indices in coagulation disorders. II. Evaluation of laboratory variables with continuous test results. Meth Inform Med 1980; 19: 201-205
    PubMedSearch in Google Scholar
  • 21 Blombäck M, Hall P, Wahlberg T. Prediktorer och indikatorer vid analys av laboratoriefynd vid von Willebrand’s sjukdom. Läkartidningen 1978; 75: 2306-2310
    PubMedSearch in Google Scholar
  • 22 Lachenbruch PA, Clarke WR. Discriminant analysis and its application in epidemiology. Meth Inform Med 1980; 19: 220-226
    PubMedSearch in Google Scholar
  • 23 Italian working group. Spectrum of von Willebrand’s disease. Br J Haematol 1977; 35: 101-112
    CrossrefPubMedSearch in Google Scholar
  • 24 Nyman D, Eriksson AW, Blombäck M, Frants RR, Wahlberg P. Recent investigations of the first bleeder family in Åland (Finland) described by von Willebrand. Thromb Haemostas 1981; 45: 73-76
    PubMedSearch in Google Scholar
  • 25 von Willebrand EA. Hereditär pseudohämofili. Finska läkarsällskapets Handlingar 1926; 68: 87-112
    PubMedSearch in Google Scholar
  • 26 Solberg HE, Skrede S, Blomhoff JP. Diagnosis of liver diseases by laboratory results and discriminant analysis. Scand J Clin lab Invest 1975; 35: 713-721
    CrossrefPubMedSearch in Google Scholar