Comparison of the Blood Coagulation Profiles of Ferrets and Rats

Takahashi, S.; Hirai, Norio; Shirai, Mitsuyuki; Ito, Katsuaki; Asai, Fumitoshi

doi:10.1292/jvms.10-0489

Cited by 18 publications

(10 citation statements)

References 11 publications

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“…These findings are in line with earlier epidemiological, clinical, animal and in vitro data [6,8,13-15,20,22-24]. Ferrets have been shown to be an adequate model to study the coagulation cascade [25-27] with PT and APTT normal values varying from 11.6-12.7 and 18.9-22.3 seconds respectively. This is comparable to our 104 pre-inoculation ferret samples (PT 11.7 (+/- 0.1) and APTT 19.8 (+/- 2.2)) [26].…”

Section: Discussionsupporting

confidence: 88%

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

et al. 2014

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BackgroundEpidemiological 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.ResultsAfter 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.ConclusionThis 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.

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Section: Discussionsupporting

confidence: 88%

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

et al. 2014

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“…In the BT experiments the baseline results were compatible with the previously reported data, and intravenously administered APACs-and UFH-modified hemostasis as shown by the prolongation of the aPTT and BT. 25,26 APAC1 and APAC2 induced 50% less bleeding and prolonged aPTT at least 15% less in comparison with UFH at the similar dose. APAC1 showed dose-dependent effects on prolonging the BT at the selected dose range while APAC2 with the doubled coupling level of heparin chains induced less bleeding.…”

Section: Discussionmentioning

confidence: 91%

Mast Cell–Derived Heparin Proteoglycans As a Model for a Local Antithrombotic

Lassila

Jouppila

2014

Semin Thromb Hemost

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Mast cell?derived heparin proteoglycans (HEP-PG) reside in vascular tissue and serve as a local antithrombotic. Heparin, as used clinically, is isolated from its protein backbone from porcine and bovine gut mucosa. The isolated heparin is an anticoagulant; however, when bound to a protein carrier the heparin conjugates will become antiplatelet agents by inhibiting collagen-induced platelet aggregation and procoagulant activity, as distinct from soluble heparin. HEP-PG, whether soluble or immobilized to a surface, inhibit platelet deposition on the collagen surface in flowing blood. Mimics of HEP-PG, can be tailored to molecules carrying both antiplatelet and anticoagulant (APAC) properties. These molecules can target the vascular injury site and take residence there. Inhibition of thrombus growth using these APACs under these conditions has been demonstrated in several animal models. Although efficacious for antiplatelet and anticoagulant effects, the bleeding time is shorter with APACs than with unfractionated heparin, suggestive of beneficial efficacy/safety ratio. These strategies may be utilized in drug development, where many vascular injury-related problems can be tackled locally.

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“…In blood coagulation assays, activated partial prothrombin time (aPTT), prothrombin time (PT) and thrombin time (TT) were measured in citrated plasma using a STart4 analyzer/ reagent combination (Diagnostica Stago, France, distributed by Roche Diagnostics KK, Tokyo, Japan) according to the manufacturer's instructions as described previously [17].…”

mentioning

confidence: 99%

“…There are 2 main types of clot detection systems: photo-optical clot detection systems and electro-mechanical clot detection systems. We used an electro-mechanical coagulation analyzer in our study, and thus our data are unlikely to be affected by variables that affect light transmission, such as hyperlipidemia [17].…”

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confidence: 99%

Shortened Blood Coagulation Times in Genetically Obese Rats and Diet-Induced Obese Mice

Kaji

Nagakubo

Hashida

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. The aim of this study was to investigate blood coagulation times in genetically obese rats and diet-induced obese (DIO) mice in order to clarify the relationship between visceral obesity and blood coagulation. WBN/Kob-Lepr fa (fa/fa) rats, a genetically obese model, exhibited a significantly shorter activated partial thromboplastin time (aPTT) and prothrombin time (PT) than age-matched Wistar rats. C57BL/6J mice fed a high-fat diet (60%), a DIO model, exhibited significantly shorter aPTT, PT and thrombin time than lean mice fed a standard diet. Higher body weight, visceral fat weight and insulin resistance were also shared by fa/fa rats and DIO mice. These results suggest that visceral obesity is related to accelerated blood coagulation in addition to disrupted metabolism of glucose and lipids. KEY WORDS: blood coagulation time, mouse, obese, rat, visceral fat.doi: 10.1292/jvms.13-0029; J. Vet. Med. Sci. 75(9): 1245-1248, 2013 The large increase in patients with metabolic syndrome which is closely correlated with visceral obesity is a problem in urgent need of a solution in developed countries, including Japan. Visceral obesity is associated with a high incidence of ischemic heart disease [4,9], and many cases are complicated by impaired glucose tolerance, hyperlipidemia and high blood pressure [6].Thrombus formation in the coronary artery with underlying arteriosclerosis is known to be a major cause of death in patients with type 2 diabetes (T2D) and dyslipidemia, which are particularly prevalent in metabolic syndrome. The blood coagulation system plays a major role in thrombus formation. However, little is known about the relationship between visceral obesity and blood coagulation. This study investigated this relationship by measuring blood coagulation times in 2 distinct visceral obesity models; the WBN/Kob-Lepr fa (fa/ fa) rat, a genetically obese model [2,7], and the C57BL/6J mouse fed a high-fat diet, a DIO model [16]. In both animal models after body weight had plateaued, blood coagulation times were compared with those of age-matched Wistar rats and lean mice fed a standard diet, respectively. Blood coagulation times measured in the present study are activated partial prothrombin time (aPTT), prothrombin time (PT) and thrombin time (TT), the most commonly used clotting time assays in mammals. aPTT, PT and TT assess the function of the intrinsic pathway, the extrinsic pathway and the common pathway, respectively [18].This study was carried out on male fa/fa rats and agematched Wistar rats (Japan SLC Inc., Hamamatsu, Japan), or male C57BL/6J mice (Charles River Laboratories Japan, Inc., Yokohama, Japan). All animals were kept in an environment at 20°C and 50 ± 5% humidity with 12 hr of light and free access to food and water. All experimental animals used in this study were handled according to the experimental animal guidelines of Azabu University. Blood glucose levels of fa/fa rats and Wistar rats were measured weekly from 6 weeks of age using blood collected from tail veins. Rats at 10 weeks ...

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Comparison of the Blood Coagulation Profiles of Ferrets and Rats

Cited by 18 publications

References 11 publications

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

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

Mast Cell–Derived Heparin Proteoglycans As a Model for a Local Antithrombotic

Shortened Blood Coagulation Times in Genetically Obese Rats and Diet-Induced Obese Mice

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