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

Summary

Percent aggregation and the aggregation rate of platelet rich plasma (PRP) in response to ristocetin (1.75 mg/ml) were measured in 20 normals and 16 patients with von Willebrand’s disease (vWd), with and without the addition of acetylsalicylic acid (ASA). Percent aggregation did not clearly distinguish between normals and patients with vWd. Aggregation rate was normal in only 2 of 16 patients, and after incubation of PRP with ASA 1 of these 2 remained normal.

The corrective effect of dilutions of platelet poor plasma (PPP) on the ristocetin response of washed platelets (von Willebrand’s factor, vWf ) was measured in 21 normals and 12 patients with vWd. All patients with vWd had abnormal levels. There was a significant correlation between aggregation rate and vWf in patients with vWd but not in normals. Both tests appear to measure closely related defects, and the aggregation rate is as specific as the vWf level for the diagnosis of clinically affected patients.

• References

• 1 Born G. V. B, and Cross M. J. 1963; The aggregation of blood platelets. Journal of Physiology 168: 178.
• 2 Firkin B, Firkin F, and Stott L. 1973; Von Willebrand’s disease type B: a newly defined bleeding diathesis. Australian and New Zealand Journal of Medicine 3: 225.
• 3 Howard M. A, and Firkin B. G. 1971; Bistocetin - a new tool in the investigation of platelet aggregation. Thrombosis et Diathesis Haemorrhagica 26: 362.
• 4 Howard M. A, Sawers B. J, and Firkin B. G. 1973; Bistocetin - a means of differentiating von Willebrand’s disease into two groups. Blood 41: 687.
• 5 Kattlove H. E, and Gomez M. H. 1974 Studies on the mechanism of ristocetin -induced platelet aggregation. In press.
• 6 Koutts J, Stott L, Sawers R. J, and Firkin B. G. 1974; Variant patterns in von Willebrand’s disease. Thrombosis Besearch 5: 557.
• 7 Laurell C. B. 1966; Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Analytical Biochemistry 15: 45.
• 8 Meyer D, Jenkins C. S. P, Dreyfus M, and Larrieu M. J. 1974; a Willebrand factor activity and antigen in von Willebrand’s disease. Lancet 1: 512.
• 9 Meyer D, Jenkins C. S. P, Dreyfus M. D, Fressinaud E, and Larrieu M. J. 1974; b Willebrand factor and ristocetin. II. Relationship between Willebrand factor, Willebrand antigen and factor VIII activity. British Journal of Haematology 28: 579.
• 10 Mielke Jnr. C. H, Kaneshiro M. M, Maher I. A, Weiner J. M, and Rapaport S. I. 1969; The standardized Ivy bleeding time and its prolongation by aspirin. Blood 34: 204.
• 11 Nilsson I. M, Blomback M, Jorpes E, Blomback B, and Johansson S. A. 1957; Von Willebrand’s disease and its correction with human plasma fraction 1-0. Acta Medica Scandinavia 159: 179.
• 12 Olsen J. D, Brockway W. J, Fass D. N, Magnuson M. A, and Bowie E. J. W. 1975 Evaluation of ristocetin - Willebrand factor assay and ristocetin-induced platelet aggregation. American Journal of Clinical Pathology. In press.
• 13 Papayannis A. G, Wood J. K, and Israels M. C. G. 1971; Factor-VIII levels, bleeding times, and platelet adhesiveness in patients with von Willebrand’s disease and in their relatives. Lancet 1: 418.
• 14 Perkins H. A. 1967; Correction of the hemostatic defects in von Willebrand’s disease. Blood 30: 375.
• 15 Proctor R. R, and Rapaport S.I. 1961; The partial thromboplastin time with kaolin. American Journal of Clinical Pathology 36: 212.
• 16 Ruggeri Z. M, Pareti F. L, Bintadish Pakaimas, and Mannucci P. M. 1974; Clotting factors in von Willebrand’s disease. Lancet 2: 105.
• 17 Salzman E. W. 1963; Measurement of platelet adhesiveness : A simple in vitro technique demonstrating an abnormality in von Willebrand’s disease. Journal of Laboratory and Clinical Medicine 62: 724.
• 18 Walsh P. N. 1973 Personal communication.
• 19 Weiss H. J, Hoyer L. W, Rickles F. R, Varma A, and Rogers J. 1973; Quantitative assay of a plasma factor deficient 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.
• 20 Weiss H. J. 1974 Personal communication.
• 21 Zimmerman T. S, Ratnoff O. D, and 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.
• 22 Zimmerman T. S, and Edgington T. S. 1973; Factor VIII coagulant activity and factor Vlll-like antigen: independent molecular entities. Journal of Experimental Medicine 138: 1015.