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To investigate the suggestion that von Willebrand factor (vWf) can substitute for fibrinogen in supporting ADP-induced aggregation of human platelets, we studied platelet reactions in two media: (1) a high calcium medium, Tyrode-albumin solution containing calcium ions in the physiological range of 2 mmol/L, and (2) a low calcium medium, modified Tyrode-albumin solution from which calcium salt was omitted (calcium ion concentration approximately 20 mumol/L). In the high calcium medium vWf even at concentrations up to six times as high as physiological, showed little or no potentiation of ADP-induced platelet aggregation, whereas fibrinogen strongly potentiated reversible aggregation without thromboxane formation or release of granule contents. In the low calcium medium, either vWf or fibrinogen supported biphasic aggregation in response to ADP, with thromboxane formation and release of granule contents. Aspirin and the thromboxane receptor blocker BM 13.177 inhibited these secondary responses to von Willebrand factor, indicating that they require thromboxane A2 formation and feedback amplification by thromboxane A2. A monoclonal antibody, 10E5, to the platelet glycoprotein IIb/IIIa complex inhibited both primary and secondary aggregation. Although vWf supports ADP-induced aggregation when the concentration of ionized calcium is in the micromolar range, it does not support ADP-induced aggregation in the presence of a concentration of ionized calcium in the physiological range, indicating that vWf probably cannot substitute for fibrinogen in supporting ADP-induced aggregation in vivo.
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
January 1986,
Transactions of the Association of American Physicians,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
August 1984,
Proceedings of the National Academy of Sciences of the United States of America,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
January 1979,
Thrombosis research,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
June 1998,
Thrombosis and haemostasis,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
August 1986,
Thrombosis research,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
December 1985,
Proceedings of the National Academy of Sciences of the United States of America,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
June 1986,
Thrombosis and haemostasis,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
January 1970,
Scandinavian journal of haematology,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
November 1989,
Blood,
E J Harfenist, and
M A Packham, and
R L Kinlough-Rathbone, and
M Cattaneo, and
J F Mustard
October 1993,
Current opinion in cell biology,
