title: Dissociation between fibrinogen and fibrin interaction with platelets in patients with different subtypes of Glanzmann's thrombasthenia: studies in an ex vivo perfusion chamber model.
abstract: To explore the possible role of a residual or variant alphaIIbbeta3 integrin (alphaIIbbeta3) in thrombogenesis, we used a new ex vivo perfusion chamber model to examine blood from patients with different subtypes of Glanzmann's thrombasthenia (GT). Non-anticoagulated blood was perfused through capillaries coated with type III collagen for 4.5 min (shear rate: 1600/s). Platelet deposition was quantified as platelet adhesion and mean thrombus size volume; fibrin and von Willebrand Factor (VWF) were specifically revealed by immunohistochemistry. In two patients with variant and in one patient with type II GT, platelet adhesion was maximal and we observed an unexpected formation of thrombi that were smaller than normal in size. These thrombi were surrounded by a thick meshwork that displayed a strong staining for fibrin and VWF. In two patients with heterozygous GT, platelet adhesion and thrombogenesis were normal. In two patients with type I GT, there was no thrombus formation, although platelet adhesion was also maximal. These data suggest the existence of a substitute pathway for thrombogenesis mediated by fibrin and possibly alphaIIbbeta3 (alphaIIbbeta3 at a reduced level, as in type II, and/or abnormal) as this fibrin network was not observed in type I GT with no alphaIIbbeta3. These interactions might facilitate haemostasis and even lead to thrombosis under certain favourable conditions. Furthermore, these data might have pharmacological relevance to the development of anti-alphaIIbbeta3 antithrombotic agents.
authors.affiliation: Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hainaud
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Brouland
authors.forename: Patrick
authors.initials: P
authors.lastname: André
authors.forename: Guy
authors.initials: G
authors.lastname: Simoneau
authors.forename: Claire
authors.initials: C
authors.lastname: Bal Dit Sollier
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
authors.forename: Jacques
authors.initials: J
authors.lastname: Caen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bellucci
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D024061:Collagen Type III / Q000502:physiology; D015194:Diffusion Chambers, Culture; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000502:physiology; D013915:Thrombasthenia / Q000097:blood* / Q000235:genetics; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D024061:Collagen Type III; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014841:von Willebrand Factor; D005337:Fibrin; D005340:Fibrinogen