Haemorrhagic and thrombotic diatheses in mouse models with thrombocytosis

Catherine Strassel; Lucia Kubovcakova; Pierre H. Mangin; Catherine Ravanat; Monique Freund; Radek C. Skoda; Cécile V. Denis; Arnaud Dupuis; Raoul Herbrecht; Christian Gachet; François Lanza

doi:10.1160/TH14-08-0667

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 113(02): 414-425
DOI: 10.1160/TH14-08-0667

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH

Haemorrhagic and thrombotic diatheses in mouse models with thrombocytosis

Catherine Strassel

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

,

Lucia Kubovcakova

⁴Department of Biomedicine, Experimental Hematology, University Hospital Basel, Basel, Switzerland

,

Pierre H. Mangin

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

,

Catherine Ravanat

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

,

Monique Freund

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

,

Radek C. Skoda

⁴Department of Biomedicine, Experimental Hematology, University Hospital Basel, Basel, Switzerland

,

Cécile V. Denis

⁵UMR_S770, INSERM, Université Paris-Sud, Le Kremlin-Bicêtre, France

,

Arnaud Dupuis

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

,

Raoul Herbrecht

⁶Department of Oncology and Hematology, Hôpital de Hautepierre, Strasbourg, France

,

Christian Gachet

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

,

François Lanza

¹INSERM UMR_S949, Strasbourg, France

²Université de Strasbourg, Strasbourg, France

³EFS-Alsace, Strasbourg, France

› Author Affiliations

Abstract

Summary

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.

Keywords

Thrombocytosis - haemorrhages - thrombotic tendency

Full Text

References

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