Acquired von Willebrand’s Syndrome in the Course of Waldenström’s Disease

SummaryAcquired von Willebrand's syndrome with a regressive evolution is described in a 66 year old man with Waldenström's disease. An inhibitor electively directed against Ristocetin cofactor activity has been demonstrated, active in vitro after incubation at 37° C. Serum fractionation showed that the inhibitor was independant of the monoclonal IgM and subsequent purification that it was IgG in nature. The results permit its classification as an auto-antibody.

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Functional studies of Willebrand factor using monoclonal antibodies

Blood ◽

10.1182/blood.v62.1.146.146 ◽

1983 ◽

Vol 62 (1) ◽

pp. 146-151 ◽

Cited By ~ 9

Author(s):

EJ Bowie ◽

DN Fass ◽

JA Katzmann

Keyword(s):

Monoclonal Antibodies ◽

Bleeding Time ◽

Functional Studies ◽

Functional Assays ◽

Cofactor Activity ◽

Willebrand Factor ◽

Ristocetin Cofactor ◽

Ristocetin Cofactor Activity

Abstract Previously described monoclonal antibodies to porcine Willebrand factor were used to study various functional assays of Willebrand factor. These antibodies comprise at least five separate specificities as determined by differential reactivity in three distinct binding assays. The antibodies were tested for their effect on the in vivo bleeding time, in vitro bleeding time, and ristocetin cofactor activity. The titers of the antibodies in a binding assay did not correlate with any inhibitory activities, and the ability to inhibit a given functional test was independent of inhibitory activity in the other assays. These data suggest that the antibodies are able to detect specific structures on Willebrand factor involved in specific functional assays and that the structure(s) involved in ristocetin cofactor activity is not identical to those mediating the in vivo or in vitro bleeding time.

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Functional studies of Willebrand factor using monoclonal antibodies

Blood ◽

10.1182/blood.v62.1.146.bloodjournal621146 ◽

1983 ◽

Vol 62 (1) ◽

pp. 146-151

Author(s):

EJ Bowie ◽

DN Fass ◽

JA Katzmann

Keyword(s):

Monoclonal Antibodies ◽

Bleeding Time ◽

Functional Studies ◽

Functional Assays ◽

Cofactor Activity ◽

Willebrand Factor ◽

Ristocetin Cofactor ◽

Ristocetin Cofactor Activity

Previously described monoclonal antibodies to porcine Willebrand factor were used to study various functional assays of Willebrand factor. These antibodies comprise at least five separate specificities as determined by differential reactivity in three distinct binding assays. The antibodies were tested for their effect on the in vivo bleeding time, in vitro bleeding time, and ristocetin cofactor activity. The titers of the antibodies in a binding assay did not correlate with any inhibitory activities, and the ability to inhibit a given functional test was independent of inhibitory activity in the other assays. These data suggest that the antibodies are able to detect specific structures on Willebrand factor involved in specific functional assays and that the structure(s) involved in ristocetin cofactor activity is not identical to those mediating the in vivo or in vitro bleeding time.

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Absence of the Largest Platelet-von Willebrand Multimers in a Patient with Lactoferrin Deficiency and a Bleeding Tendency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648440 ◽

1992 ◽

Vol 67 (03) ◽

pp. 320-324 ◽

Cited By ~ 11

Author(s):

Robert I Parker ◽

Laurie P McKeown ◽

John I Gallin ◽

Harvey R Gralnick

Keyword(s):

Young Male ◽

Surface Expression ◽

Bleeding Tendency ◽

Primary Hemostasis ◽

Normal Platelet ◽

Cofactor Activity ◽

Von Willebrand ◽

Ristocetin Cofactor ◽

Ristocetin Cofactor Activity

SummaryWe have studied a young male with lactoferrin deficiency and a bleeding tendency responsive to cryoprecipitate. This child has had increased bleeding following surgical procedures and a variably prolonged template bleeding time. The patient has a normal platelet count, normal in vitro platelet ATP secretion and aggregation in response to a variety of agonists, and normal concentration of plasma-von Willebrand factor ristocetin cofactor activity and antigen. Analysis of plasma-vWf multimers by agarose gel electrophoresis consistently demonstrated a subtle decrease in the largest vWf multimers. In contrast, analysis of the patient’s platelet-vWf revealed normal vWf:Ag, decreased vWf ristocetin cofactor activity, and a striking absence of the high and intermediate size molecular weight vWf multimers. Analysis of surface bound platelet-vWf demonstrated normal amounts on the surface of unstimulated platelets, but after thrombin stimulation the platelet-vWf surface expression did not increase. This lack of increased platelet-vWf surface expression resulted from decreased binding of secreted platelet-vWf to be surface of stimulated platelets. These data suggest that the patient’s bleeding tendency may be related to a defect in his platelet-vWf structure and/or mobilization. This case represents a unique demonstration of an abnormality of platelet-vWf in the presence of normal plasma-vWf, and supports the data indicating an important role for platelet-vWf in primary hemostasis.

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Plasma Derived von Willebrand Factor Preparations: Collagen Binding and Ristocetin Cofactor Activities

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657654 ◽

1997 ◽

Vol 78 (02) ◽

pp. 930-933 ◽

Cited By ~ 11

Author(s):

Ping Chang ◽

D L Aronson

Keyword(s):

Von Willebrand Factor ◽

Functional Activity ◽

Binding Activity ◽

Collagen Binding ◽

Binding Function ◽

Cofactor Activity ◽

Von Willebrand ◽

Willebrand Factor ◽

Ristocetin Cofactor ◽

Ristocetin Cofactor Activity

SummaryFive plasma preparations (11 lots) used in the treatment of von Willebrand’s disease (vWD) were evaluated. The collagen binding function of von Willebrand factor (vWF) containing preparations was compared with the ristocetin cofactor activity and the vWF antigen. Some preparations have higher ratio of functional activity (ristocetin cofactor and collagen binding) relative to the antigen than is found in normal plasma. The ristocetin cofactor activity and the collagen binding activity are tightly correlated (r = .95). Ultracentrifugal (UCF) analysis was used to compare the size distribution of vWf antigen, ristocetin cofactor and collagen binding activity. The sedimentation of all of the vWF parameters in the plasma products was slower than in plasma. In plasma products the ristocetin cofactor activity sediments the most rapidly, the collagen binding activity is slower and the antigen the slowest. The collagen/antigen ratio decreases with decreasing vWF size. Assignment of potency to vWF containing preparations utilizing the collagen binding activity may be more precise and as accurate as with the traditional ristocetin cofactor assay.

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Selective absence of large forms of factor VIII/von Willebrand factor in acquired von Willebrand's syndrome. Response to transfusion

Blood ◽

10.1182/blood.v54.3.600.600 ◽

1979 ◽

Vol 54 (3) ◽

pp. 600-606 ◽

Cited By ~ 34

Author(s):

D Meyer ◽

D Frommel ◽

MJ Larrieu ◽

TS Zimmerman

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Von Willebrand Disease ◽

Procoagulant Activity ◽

Factor Viii Related Antigen ◽

Cofactor Activity ◽

Von Willebrand ◽

Willebrand Factor ◽

Ristocetin Cofactor ◽

Ristocetin Cofactor Activity

Abstract A previously healthy elderly man with mucocutaneous bleeding was found to have a benign monoclonal IgG gammapathy associated with criteria for severe von Willebrand disease (Factor VIII procoagulant activity, Factor-VIII-related antigen, and ristocetin cofactor activity, less than 10% of normal). Associated qualitative abnormalities of factor VIII/von Willebrand factor were demonstrated by radiocrossed immunoelectrophoresis and immunoradiometric assay. The late clinical onset and negative family history are in favor of an acquired form of vWD. The monoclonal gammapathy and abnormalities of factor VIII/von Willebrand factor have been stable over a 10-yr period. No inhibitor to Factor VIII procoagulant activity, ristocetin cofactor activity, or Factor-VIII-related antigen could be demonstrated. Following transfusion of cryoprecipitate (with a normal cross immunoelectrophoretic pattern), there was a rapid removal of the large forms of Factor.-VIII-related antigen, paralleled by a decay of ristocetin cofactor activity. The transfusion study of this patient with acquired von Willebrand disease type II (variant of von Willebrand disease) serves to emphasize the relationship between polydispersity of Factor VIII/von Willebrand Factor and functional heterogeneity.

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Variant von Willebrand's disease and pregnancy

Blood ◽

10.1182/blood.v58.5.873.873 ◽

1981 ◽

Vol 58 (5) ◽

pp. 873-879 ◽

Cited By ~ 27

Author(s):

W Hanna ◽

D McCarroll ◽

T McDonald ◽

P Painter ◽

J Tuller ◽

...

Keyword(s):

Factor Viii ◽

Half Life ◽

Clinical Course ◽

Procoagulant Activity ◽

Von Willebrand's Disease ◽

Factor Viii Related Antigen ◽

Coagulation Profile ◽

Cofactor Activity ◽

Ristocetin Cofactor ◽

Ristocetin Cofactor Activity

Abstract The clinical course and coagulation profile of a pregnant patient with variant von Willebrand's disease were followed from the second trimester through puerperium. The clinical course was characterized by a normal delivery and absence of abnormal bleeding or need for replacement therapy. The coagulation profile demonstrated an increase in factor VIII procoagulant activity, factor-VIII-related antigen, and platelet aggregation activity in response to ristocetin prior to delivery. Postpartum, these factors decreased to prepregnancy values with distinctly different patterns. Factor VIII procoagulant activity continued to rise for 5 days after delivery and then decreased with a half-life of approximately 6 days. Factor-VIII-related antigen began to decrease just prior to delivery, displaying a half-life or approximately 6 days. Ristocetin cofactor activity, however, dropped immediately postpartum and displayed a half-life of approximately 6 hr. The ristocetin cofactor activity was associated with factor-VIII- related antigen, which displayed a significantly smaller molecular weight than does normal factor-VIII-related antigen. Larger aggregates of factor-VIII-related antigen. Larger aggregates of factor-VIII- related antigen did not appear during the pregnancy, and ristocetin cofactor activity could not be demonstrated in fragments of less than 0,8 x 10(6).

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