Open Access Highly Accessed Research article

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

Marco Goeijenbier1*, Eric CM van Gorp1, Judith MA Van den Brand1, Koert Stittelaar2, Kamran Bakhtiari3, Joris JTH Roelofs4, Geert van Amerongen1, Thijs Kuiken1, Byron EE Martina1, Joost CM Meijers3 and Albert DME Osterhaus12

Author Affiliations

1 Department of Viroscience laboratory, Erasmus MC, room ee1671, Rotterdam, CE 50 3015, The Netherlands

2 Viroclinics Biosciences BV, Rotterdam, The Netherlands

3 Department Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

4 Department Pathology, Academic Medical Center, Amsterdam, The Netherlands

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BMC Microbiology 2014, 14:134  doi:10.1186/1471-2180-14-134

Published: 30 May 2014

Abstract

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.

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