Fasciola hepatica alters coagulation parameters in sheep plasma in vivo and in vitro

Abstract

The blood-sucking activities of the liver fluke, Fasciola hepatica, are likely to cause alterations in coagulation during the course of infection; and the effect of F. hepatica on various coagulation parameters was studied during the course of acute and chronic fasciolosis of sheep over a period of 17 weeks. Whole blood and plasma samples from infected sheep (with 800 metacercariae each) and uninfected controls were collected weekly until 17 weeks post-infection (w.p.i.) and the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were determined. Additionally, adult F. hepatica were recovered from bile ducts, incubated for the production of excretory/secretory products (ESP) or homogenised and the effect of fluke products on APTT, PT and TT was determined. Anaemia was evident in infected sheep from 8 w.p.i. until 17 w.p.i. Plasma APTT was accelerated during 8, 9, 12, 14, 16 and 17 w.p.i., while PT was prolonged at 8-11 w.p.i. and TT at 10, 14 and 17 w.p.i. Addition of worm ESP or homogenate to plasma resulted in an enhancement of the intrinsic pathway (APTT) together with a prolongation of the extrinsic and common pathways (PT, TT) of coagulation. It was concluded that F. hepatica contains and releases substances that may contribute to coagulation changes in vivo. Further characterisation of the active substance(s) in vitro revealed heat inactivation, a size >30 kDa and inhibition by the proteinase inhibitors Complete and EDTA for the APTT-accelerating substance(s). The TT-deceleration, in contrast, was increased after heating.

Host-Parasite Relationships in Porcine Ascariosis: Anticoagulant Potential of the Third Larval Stage of Ascaris suum as a Possible Survival Mechanism

“…The results obtained in the present study revealed that AsL3C and AsL3ES inhibited the intrinsic, extrinsic and/or common pathways of the coagulation cascade before the transformation of fibrinogen into fibrin, since the APTT and PT assays were significantly altered in the presence of both antigenic extracts, but no significant change was found in the TT assay. These results correlate with those obtained in other studies using similar methodologies for both helminth and arthropod parasites [33][34][35][36][37] as well as reinforce the studies developed with the adult worms of A. suum and its closely related species A. lumbricoides during the 1980s and 1990s [38,39].…”

“…This mechanism could occur in the AsL3 immediate intravascular habitat or at a systemic level, since similar results were obtained in this study by both their cuticle and excretory/secretory products. Therefore, this strategy could help the parasite to migrate, evade the host immune system and survive, as it has been postulated for other nematode and trematode parasites [31,35,37,60]. In addition, coagulation inhibition by AsL3 could contribute to aggravate the pathological processes produced in the infected pigs.…”

Transcriptional analysis identifies key genes involved in metabolism, fibrosis/tissue repair and the immune response against Fasciola hepatica in sheep liver

“…A cardinal sign of fascioliasis is anaemia, particularly as a consequence of a large fluke burden, which often significantly affects the health and productivity of animals. Several studies have shown evidence supporting the significant negative effect that Fasciola has on metabolic mechanisms associated iron and iron-binding capacity [ 35 ], coagulation [ 37 ] and/or various biochemical parameters in blood [ 71 ], providing insights into the consequences of and responses to major blood loss in infected animals. In the present study, we infected sheep with a relatively small number (n = 180) of metacercariae.…”

“…Cellular changes in the infected liver are associated with a disruption of the mitochondrial electron transport chain, and a substantial loss of cytochrome P450 activity and glycogen content in the left lobe [ 3 ]. Physiological changes in infected animals can include glycaemia [ 33 ], lipidaemia [ 34 ], a reduction in plasma ascorbic acid [ 35 ] and testosterone catabolism [ 36 ] as well as an increase in iron and iron-binding capacity [ 35 ], and a variable effect on coagulation [ 37 ]. However, the specific molecular mechanisms underpinning these changes are not well understood.…”

Liver fluke in Irish sheep: prevalence and associations with management practices and co-infection with rumen fluke

“…In sheep, liver fluke infection affects productivity and welfare [3]. It is a predisposing risk factor for mastitis [6] and drop in coagulation parameters [7]. The ingestion of large numbers of infective stages of the parasite can cause a highly pathogenic sub-acute presentation in lambs, characterised by hepatic haemorrhage and lesions, resulting in sudden death [1, 8].…”