title: Defective collagen-induced platelet activation in two patients with malignant haemopathies is related to a defect in the GPVI-coupled signalling pathway.
abstract: The occurrence of a thrombocytopathy concomitantly to the development of a malignant haemopathy has been reported for some time, but little is known about the mechanism(s) involved in the platelet dysfunction. Platelet glycoprotein VI (GPVI) has now been identified as a principal platelet receptor for collagen. In this paper, we report the cases of two patients with a myelodysplasia and a B lymphopathy, respectively, who presented with thrombocytopathy in relation to a defective GPVI-mediated platelet reactivity to collagen. Thus, with regard to the different steps of adhesion, activation secretion or aggregation, patients' platelet responses to collagen and to the GPVI specific agonists, collagen related peptide (CRP) or convulxin were null or dramatically impaired. Platelet responses to other agonists ADP, TRAP, Arachidonic acid were normal or showed only a moderate decrease. GPVI content was repeatedly normal, and binding of specific ligands, such as convulxin, satisfactory. Nevertheless, specific activating monoclonal antibodies and convulxin failed to induce platelet secretion; collagen, CRP or convulxin were unable to provoke calcium mobilisation. Furthermore, using a perfusion chamber model, we showed that ex vivo collagen-induced thrombi formation was very impaired. Taken together, these data provide evidence, for the first time, of an acquired defect in GPVI-mediated platelet reactivity to collagen, which reflects data observed in constitutional GPVI deficiencies, in two patients with malignant haemopathies.
authors.affiliation: AP-HP, Hôpital Lariboisière, Laboratory of Haematology, 2, rue Ambroise Paré, 75010 Paris, France. sylvia.bellucci@lrb.ap-hop-paris.fr
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bellucci
authors.forename: Marie G
authors.initials: MG
authors.lastname: Huisse
authors.forename: Bernadette
authors.initials: B
authors.lastname: Boval
authors.forename: Patricia
authors.initials: P
authors.lastname: Hainaud
authors.forename: Annie
authors.initials: A
authors.lastname: Robert
authors.forename: Françoise
authors.initials: F
authors.lastname: Fauvel-Lafève
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
mesh_terms: D000368:Aged; D001791:Blood Platelet Disorders / Q000209:etiology*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000150:complications; D006801:Humans; D015448:Leukemia, B-Cell / Q000097:blood / Q000150:complications; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000150:complications; D015539:Platelet Activation / Q000187:drug effects; D010979:Platelet Function Tests; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D015398:Signal Transduction; D013917:Thrombin / Q000096:biosynthesis
chemical_list: D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen; D013917:Thrombin