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Haemorrhagic and thrombotic diatheses in mouse models with thrombocytosis.
- Source :
-
Thrombosis and haemostasis [Thromb Haemost] 2015 Feb; Vol. 113 (2), pp. 414-25. Date of Electronic Publication: 2014 Oct 09. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Arteries pathology
Blood Coagulation
Blood Platelets metabolism
Carotid Arteries physiopathology
Collagen metabolism
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proportional Hazards Models
Receptors, Thrombopoietin metabolism
Thromboembolism physiopathology
Thrombopoietin metabolism
Thrombosis physiopathology
Transgenes
Hemorrhage blood
Thrombocytosis blood
Subjects
Details
- Language :
- English
- ISSN :
- 2567-689X
- Volume :
- 113
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Thrombosis and haemostasis
- Publication Type :
- Academic Journal
- Accession number :
- 25298269
- Full Text :
- https://doi.org/10.1160/TH14-08-0667