Defective platelet-fibrinogen interaction in hereditary canine thrombopathia.
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.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D000001:Calcimycin / Q000494:pharmacology; D002448:Cell Adhesion; D004283:Dog Diseases / Q000235:genetics / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006023:Glycoproteins / Q000032:analysis; D007122:Immunoelectrophoresis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008854:Microscopy, Electron; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D012701:Serotonin / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*
D000227:Adenine Nucleotides; D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D012701:Serotonin; D000001:Calcimycin; D005340:Fibrinogen; D004837:Epinephrine