Activation of coagulation and tissue fibrin deposition in experimental influenza in ferrets

BMC Microbiology

Albert DME Osterhaus³  Joost CM Meijers²  Byron EE Martina⁴  Thijs Kuiken⁴  Geert van Amerongen⁴  Joris JTH Roelofs¹  Kamran Bakhtiari²  Koert Stittelaar³  Judith MA Van den Brand⁴  Eric CM van Gorp⁴  Marco Goeijenbier⁴ 

[1] Department Pathology, Academic Medical Center, Amsterdam, The Netherlands;Department Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;Viroclinics Biosciences BV, Rotterdam, The Netherlands;Department of Viroscience laboratory, Erasmus MC, room ee1671, Rotterdam, CE 50 3015, The Netherlands

关键词: Consumption coagulopathy;    H5N1 subtype;    H1N1 subtype;    H3N2 subtype;    Influenza A virus (Human);   

Others  :  1141028
DOI  :  10.1186/1471-2180-14-134

 received in 2014-03-10, accepted in 2014-05-23,  发布年份 2014

【 摘 要 】

Background

Epidemiological studies relate influenza infection with vascular diseases like myocardial infarction. The hypothesis that influenza infection has procoagulant effects on humans has been investigated by experimental animal models. However, these studies often made use of animal models only susceptible to adapted influenza viruses (mouse adapted influenza strains) or remained inconclusive. Therefore, we decided to study the influence of infection with human influenza virus isolates on coagulation in the well-established ferret influenza model.

Results

After infection with either a seasonal-, pandemic- or highly pathogenic avian influenza (HPAI-H5N1) virus strain infected animals showed alterations in hemostasis compared to the control animals. Specifically on day 4 post infection, a four second rise in both PT and aPTT was observed. D-dimer concentrations increased in all 3 influenza groups with the highest concentrations in the pandemic influenza group. Von Willebrand factor activity levels increased early in infection suggesting endothelial cell activation. Mean thrombin-antithrombin complex levels increased in both pandemic and HPAI-H5N1 virus infected ferrets. At tissue level, fibrin staining showed intracapillary fibrin deposition especially in HPAI-H5N1 virus infected ferrets.

Conclusion

This study showed hemostatic alterations both at the circulatory and at the tissue level upon infection with different influenza viruses in an animal model closely mimicking human influenza virus infection. Alterations largely correlated with the severity of the respective influenza virus infections.

【 授权许可】

   
2014 Goeijenbier et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 3.

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