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Abstract
The adhesion of platelets to subendothelium exposed to flowing blood involves two
distinct morphological stages: (1) platelet contact (C), the initial attachment of
unspread, discoid platelets to the subendothelium, and (2) spread platelets (S), the
attachment that results as contact platelets spread on the surface and become more
firmly bound to it. A defect in either initial platelet attachment or platelet spreading
can result in reduced levels of platelet adhesion (C + S). The combined observation
of decreased platelet adhesion (C + S) and increased platelet contact (C) has been
previously utilized to conclude that a defect exists in the ability of platelets to
spread on subendothelium in von Willebrand's disease. In this present investigation,
we demonstrate, by modeling the contact and spreading stages of platelet adhesion
as a classic set of reactions in series, that the combination of reduced adhesion
(C + S) and increased contact (C) is inconclusive with regard to the nature of the
adhesion defect in von Willebrand's disease. Decreased adhesion (C + S) coupled with
increased platelet contact (C) can result from either decreased rates of initial attachment
or decreased rates of spreading. In fact, given the complexity of the temporal behavior
of platelet contact (C) and platelet spreading (S), and the relatively small fraction
(<10%) of the platelets that are in contact (C) at any time, we conclude that a determination
of the nature of the adhesion (C + S) defect in von Willebrand's disease is not statistically
feasible under conditions in which both contact and spreading occur simultaneously.
Experiments were conducted in which blood anticoagulated with EDTA was exposed to
subendothelium digested with α-chymotrypsin for periods of 10 and 40 min. Under such
conditions, platelet spreading (S) was substantially inhibited so that the predominant
platelet interaction (>80%) on the subendothelium was platelet contact (C). Values
of platelet adhesion (C + S) in von Willebrand's disease were significantly reduced
(p < 0.05) compared with normal values at both exposure times. Thus we conclude that
the defect in platelet adhesion (C + S) in von Willebrand's disease appears to be
associated with a reduced ability of platelets to attach to the surface rather than
their inability to spread on the surface.
Abbreviations:
Percentage of surface covered by unspread platelets ((C)), platelet adhesion percentage of surface covered by platelets ((C + S)), percentage of surface covered by spread platelets ((S)), International Unit ((U)), reaction rate constant for platelet contact ((kc)), reaction rate constant for platelet spreading ((ks)), reaction rate constant for platelet detachment ((kd)), ethylenediamine tetraacetic acid ((EDTA)), factor VIII/von Willebrand factor ((FVIII VWF)), factor VIII—related antigen ((VIIIR:Ag)), factor VIII—related ristocetin co-factor ((VIIIR:RCo)), factor VIII coagulant activity ((VIII:C)), defined by equations in the Appendix (a1 by equation A3, a2 by equation A4, a3 by equation A5, a4 by equation A6)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
June 7,
1983
Received:
February 8,
1983
Footnotes
☆This work was done in part during the tenure of an Established Investigatorship of the American Heart Association and supported in part by grants HL 27346 and HL 27204 from the U. S. Public Health Service.
☆☆Several patients with von Willebrand's disease were made available through the assistance of Dr. Marjorie Zucker and Dr. Richard Lipton.
Identification
Copyright
© 1983 Published by Elsevier Inc.
