Defective platelet-fibrinogen interaction in hereditary canine
thrombopathia
JL Catalfamo, SL Raymond, JG White and WJ Dodds
A unique, intrinsic, hereditary canine platelet disorder attributable to
abnormal fibrinogen receptor availability is described. Thrombopathic
platelets from 13 severely affected basset hounds failed to aggregate in
response to all agonists tested except thrombin. Normal platelet
interaction with the various stimuli was inferred on the basis of their
ability to elicit unimpaired shape change in thrombopathic platelets. No
quantitative differences in major platelet membrane glycoproteins,
intraplatelet fibrinogen, adenine nucleotides, or serotonin uptake were
detected. Dense granule secretion was impaired. The ultrastructural
appearance of thrombopathic platelets was normal. Fibrinogen-platelet
interaction was evaluated by reacting platelet-rich plasma (PRP) with
fibrinogen coupled to polymeric acrylonitrile beads and scoring the extent
of stimulus-induced agglutination. The aggregatory responses of normal and
thrombopathic platelets were closely correlated with fibrinogen receptor
availability. In contrast to human platelets, epinephrine-stimulated canine
platelets did not interact with immobilized fibrinogen, and arachidonate
generally induced only weak agglutination. Thrombopathic platelets
agglutinated fibrinogen beads at reduced rates when stimulated with
physiologic doses of thrombin and high-dose calcium ionophore, A23187. Our
data suggest that thrombin-mediated induction of canine platelet fibrinogen
receptors may proceed by pathway(s) alternate to those shared by other
platelet agonists, and/or that secreted granule constituents may act
synergistically with thrombin to overcome inhibition of signal-response-
coupled reactions mediating the interaction of fibrinogen with its
receptor. This congenital platelet defect provides further evidence, in a
species other than human, for the pivotal role of fibrinogen receptor
induction in platelet aggregation.
Volume 67,
Issue 6,
pp. 1568-1577,
06/01/1986
Copyright © 1986 by The American Society of Hematology
