Thromb Haemost 1976; 36(01): 078-085
DOI: 10.1055/s-0038-1648011
Original Article
Schattauer GmbH

Family Studies of Patients with Reduced Ristocetin Aggregation and Abnormalities of Factor VIII and/or Platelet Function

H Ekert
1   Research Foundation, Royal Children’s Hospital, Parkville, Victoria, 3052, Australia.
,
R Ananthakrishnan
1   Research Foundation, Royal Children’s Hospital, Parkville, Victoria, 3052, Australia.
,
R. H Muntz
1   Research Foundation, Royal Children’s Hospital, Parkville, Victoria, 3052, Australia.
,
S Dowling
1   Research Foundation, Royal Children’s Hospital, Parkville, Victoria, 3052, Australia.
,
S D’Souza
1   Research Foundation, Royal Children’s Hospital, Parkville, Victoria, 3052, Australia.
› Author Affiliations
Further Information

Publication History

Received 04 August 1975

Accepted 04 February 1976

Publication Date:
03 July 2018 (online)

Summary

Factor VIII procoagulant activity (VIIIc), antigen (vWa), mobility of the antigen on two dimensional Immunoelectrophoresis and platelet function were studied in 9 families with reduced ristocetin induced platelet aggregation rate (RIPA) and/or deficiency of plasma factor(s) required for ristocetin aggregation of washed normal platelets (vWf). The families could be subdivided into 4 groups. Group I showed dominant inheritance and reduced levels of VIIIc and vWa characteristic of typical von Willebrand’s disease. All patients had reduced vWf and in 7 of 10 RIPA was reduced. Group II showed normal levels of VIIIc but reduced vWa. All showed reduced vWf but RIPA was reduced in one patient only. There was a good correlation between vWf and vWa and VIIIc in both groups. The bleeding time correlated with vWf in group I but not group II. Group III showed normal or nearly normal VIIIc and vWa but there was an increased mobility of vWa compared to normals and to groups I and II. RIPA was markedly reduced as was the vWf in one patient. Group IV is represented by one child with a strong family history of bleeding, who had reduced RIPA and defective platelet release reaction. The vWf in this child was normal and the ratio between VIIIc and vWa was similar to that seen in carriers of haemophilia. This spectrum of abnormalities of ristocetin aggregation justifies the use of the term ‘von Willebrand’s syndrome’.

 
  • References

  • 1 Bennett B, Ratnoff O. D, Levin J. 1972; Immunologie studies in von Willebrand’s disease: evidence that the antihaemophilic factor (AHF) produced after transfusion lacks an antigen associated with normal AHF and the inactive material produced by patients with classic haemophilia. Journal of Clinical Investigation 51: 2597.
  • 2 Dowling S. V, Muntz R. H, D’Souza S, Ekert H. 1975a Ristocetin in the diagnosis of von Willebrand’s disease: A comparison of rate and percent of aggregation with levels of the plasma factor(s) necessary for ristocetin aggregation. Thrombosis et Diathesis Haemorrhagica 34: 465.
  • 3 Dowling S. V, Muntz R. H, D’Souza S, Ekert H. 1975b Platelet release abnormality associated with a variant of von Willebrand’s disease. Blood. (In press.)
  • 4 Howard M. A, Firkin B. G. 1971; Ristocetin - a new tool in the investigation of platelet aggregation. Thrombosis et Diathesis Haemorrhagica 26: 362.
  • 5 Howard M. A, Sawers R. J, Firkin B. G. 1973; Ristocetin: a means of differentiating von Willebrand’s disease into two groups. Blood 41: 687.
  • 6 Kernoff P. B. A, Gruson R, Rizza C. R. 1974; Avariant of factor VIII related antigen. British Journal of Haematology 26: 435.
  • 7 Meyer D, Jenkins C. S, Dreyfus M, Larrieu M. J. 1973; Experimental model for von Willebrand’s disease. Nature Lond 243: 293.
  • 8 Muntz R. H, Ekert H, Helliger H. 1974; Properties of post-infusion factor VIII in von Willebrand’s disease. Thrombosis Research 5: 111.
  • 9 Newman J, Johnson A. J, Karpatkin M. H, Puszkin S. 1971; Methods for the production of clinically effective intermediate and high-purity factor VIII concentrates. British Journal of Haematology 21: 1.
  • 10 Weiss H. J, Rogers J, Brand H. 1973a Defective ristocetin induced platelet aggregation in von Willebrand’s disease and its correlation by factor VIII. Journal of Clinical Investigation 52: 2697.
  • 11 Weiss H. J, Hoyer L. W, Rickles F. R, Varma A, Rogers J. 1973b Quantitative assay of a plasma factor diffident in von Willebrand’s disease that is necessary for platelet aggregation; relationship to factor VIII procoagulant activity and antigen content. Journal of Clinical Investigation 52: 2708.
  • 12 Weiss H. J. 1975; Abnormalities of factor VIII and platelet aggregation–use of ristocetin in diagnosing the von Willebrand syndrome. Blood 45: 403.
  • 13 Zjmmerman T. S, Ratnoff O. D, Powell A. E. 1971; 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. Journal of Clinical Investigation 50: 244.