Catalfamo J L, Raymond S L, White J G, Dodds W J
Blood. 1986 Jun;67(6):1568-77.
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.
本文描述了一种独特的、内在的、遗传性犬血小板疾病，其病因是纤维蛋白原受体可用性异常。13只严重受影响的巴吉度猎犬的血小板病性血小板，除凝血酶外，对所有测试的激动剂均无聚集反应。根据它们在血小板病性血小板中引发正常形状变化的能力，推断正常血小板与各种刺激物的相互作用。未检测到主要血小板膜糖蛋白、血小板内纤维蛋白原、腺嘌呤核苷酸或5-羟色胺摄取的定量差异。致密颗粒分泌受损。血小板病性血小板的超微结构外观正常。通过使富含血小板的血浆（PRP）与偶联到聚合丙烯腈珠上的纤维蛋白原反应，并对刺激诱导的凝集程度进行评分，来评估纤维蛋白原与血小板的相互作用。正常血小板和血小板病性血小板的聚集反应与纤维蛋白原受体可用性密切相关。与人类血小板不同，肾上腺素刺激的犬血小板不与固定化纤维蛋白原相互作用，花生四烯酸通常仅诱导微弱的凝集。当用生理剂量的凝血酶和高剂量钙离子载体A23187刺激时，血小板病性血小板凝集纤维蛋白原珠的速率降低。我们的数据表明，凝血酶介导的犬血小板纤维蛋白原受体诱导可能通过与其他血小板激动剂共享的途径不同的途径进行，和/或分泌的颗粒成分可能与凝血酶协同作用，以克服介导纤维蛋白原与其受体相互作用的信号-反应偶联反应的抑制。这种先天性血小板缺陷在人类以外的物种中进一步证明了纤维蛋白原受体诱导在血小板聚集中的关键作用。
