Experimental infection of horses with African horse sickness virus results in overt disseminated intravascular coagulation

用非洲马瘟病毒感染马匹的实验结果显示,马匹会出现明显的弥散性血管内凝血。

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Abstract

BACKGROUND: African horse sickness (AHS), caused by the vector-borne African horse sickness virus (AHSV), is endemic to sub-Saharan Africa and infection results in high mortality in naïve equine populations. Clinical signs include submucosal petechiae and prolonged bleeding post venepuncture indicative of hypocoagulation. Pathological activation of haemostasis may result from tissue factor expression as a result of vascular endothelial damage or dysfunction, the proposed pathologic mechanism in AHS, potentially resulting in disseminated intravascular coagulation (DIC). OBJECTIVES: To describe haemostatic changes during experimental AHSV infection and to characterise DIC using plasma-based and viscoelastic assays. STUDY DESIGN: In vivo experiments. METHODS: Four horses were experimentally infected with AHSV. Blood samples were obtained before infection, then every 24 h until humane euthanasia. Haematology and thromboelastography (TEG) were performed and prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer concentrations, as well as activities of antithrombin (AT) and coagulation factors II, VII, VIII, X, and XII were measured. RESULTS: Over the disease course, TEG variables showed increased clot initiation time (R) and decreased α-angle, maximum amplitude (MA), and clot strength (G). The velocity curve showed decreased maximum rate of thrombus generation (MRTG) and thrombus generation (TG), and increased time to maximum rate of thrombus generation (TMRTG). Prothrombin time, aPTT and D-dimer concentration increased while AT activity decreased. All horses developed severe thrombocytopenia. CONCLUSIONS: Horses experimentally infected with AHSV developed a consumptive coagulopathy with a bleeding phenotype. These findings fulfil the criteria of overt DIC characterised by procoagulant activation, inhibitor consumption and increased fibrinolytic activity.

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