title: Haemorrhagic and thrombotic diatheses in mouse models with thrombocytosis.
abstract: We studied haemostasis in two mouse models with thrombocytosis caused by different pathogenic mechanisms. In one strain (Yall;Mpl-/-) thrombocytosis is driven by a misbalance between thrombopoietin and its receptor, whereas in the other strain, thrombocytosis is caused by expressing a human JAK2-V617F transgene (FF1) that depends on activation by Cre-recombinase (VavCre;FF1, MxCre;FF1). Thrombotic responses were increased following some, but not all types of challenges. In a vaso-occlusive thrombotic model following collagen-adrenaline injection we found increased mortality in both strains. Arterial thrombosis, examined after ferric chloride-induced carotid injury, was accelerated but with little impact on maximal thrombus size. In a vena cava stasis model, clots were of similar size as in wild-type controls, but exhibited a different composition with a higher platelet to fibrin ratio. Both thrombocytosis strains displayed increased haemorrhagic tendency in a tail bleeding assay. Yall;Mpl and VavCre;FF1 displayed a lower proportion of the more reactive high-molecular-weight forms of von Willebrand factor in their plasma, mimicking essential thrombocythaemia with very high platelet counts. Bleeding could not be explained by clear defects in platelet activation, which were normal or only weakly decreased. In conclusion, these models of thrombocytosis recapitulate several features of the haemorrhagic and thrombotic diatheses in ET and PV demonstrating potentials but also some limitations to study these major complications.
authors.forename: Catherine
authors.initials: C
authors.lastname: Strassel
authors.forename: Lucia
authors.initials: L
authors.lastname: Kubovcakova
authors.forename: Pierre H
authors.initials: PH
authors.lastname: Mangin
authors.forename: Catherine
authors.initials: C
authors.lastname: Ravanat
authors.forename: Monique
authors.initials: M
authors.lastname: Freund
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
authors.forename: Cécile V
authors.initials: CV
authors.lastname: Denis
authors.forename: Arnaud
authors.initials: A
authors.lastname: Dupuis
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.affiliation: François Lanza, UMR S_949 - EFS-Alsace, 10, rue Spielmann, 67065 Strasbourg Cedex, France, Tel.: +33 388 21 25 25, Fax: +33 388 21 25 21, E-mail: francois.lanza@efs-alsace.fr.
authors.forename: François
authors.initials: F
authors.lastname: Lanza
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D002339:Carotid Arteries / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006470:Hemorrhage / Q000097:blood*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016016:Proportional Hazards Models; D053628:Receptors, Thrombopoietin / Q000378:metabolism; D013922:Thrombocytosis / Q000097:blood*; D013923:Thromboembolism / Q000503:physiopathology; D013926:Thrombopoietin / Q000378:metabolism; D013927:Thrombosis / Q000503:physiopathology; D019076:Transgenes
chemical_list: D053628:Receptors, Thrombopoietin; D003094:Collagen; D013926:Thrombopoietin
keywords: Thrombocytosis; haemorrhages; thrombotic tendency