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Abstract
Schistosomes are parasitic platyhelminths that currently infect over 200 million people and cause the chronic debilitating disease schistosomiasis. While these large intravascular parasites can disturb blood flow, surprisingly they do not appear to provoke thrombus formation around them in vivo. In order to determine if the worms can alter their local environment to impede coagulation, we incubated adult worms (50 pairs) in murine blood (500 µl) for 1 h at 37 °C and, using thromboelastography (TEG), we compared the coagulation profile of the blood with control blood that never contained worms. Substantial differences were apparent between the two profiles. Blood that had been exposed to schistosomes clotted more slowly and yielded relatively poor, though stable, thrombi; all TEG measures of blood coagulation (R, K, α-angle, MA, G and TMA) differed significantly between conditions. No fibrinolysis (as determined by LY30 and LY60 values) was detected in either case. The observed TEG profile suggests that the worms are acting as local anti-coagulants. Blood recovered from schistosome-infected mice, however, does not behave in this way. At an early time point post infection (4-weeks), the TEG profile of infected murine blood is essentially the same as that of control blood. However at a later time point (7-weeks) infected murine blood clots significantly faster than control blood but these clots also break down faster. The R, K, α-angle, and TMA measures of coagulation are all significantly different between the control versus infected mice as are the LY30 and LY60 values. This profile is indicative of a hypercoagulable state with fibrinolysis and is akin to that seen in human patients with advanced schistosomiasis.
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Acknowledgments
This work was funded by NIH-NIAID Grant AI056273. Infected snails were provided by BRI via the NIAID schistosomiasis resource center under NIH-NIAID Contract No. HHSN272201000005I. We thank Qiang Wang for technical assistance.
Author contribution
Conceived and designed the experiments: A. A. Da’dara and P. J. Skelly. Performed the experiments: A. A. Da’dara. Analyzed the data: A. A. Da’dara, A. M. de Laforcade, P. J. Skelly. Wrote the paper, A. A. Da;’dara, P. J. Skelly.
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Department of Infectious Disease and Global Health, Molecular Helminthology Laboratory, Tufts University, North Grafton, MA, USA
Akram A. Da’dara & Patrick J. Skelly
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA
Armelle M. de Laforcade
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Correspondence toPatrick J. Skelly.
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Da’dara, A.A., de Laforcade, A.M. & Skelly, P.J. The impact of schistosomes and schistosomiasis on murine blood coagulation and fibrinolysis as determined by thromboelastography (TEG).J Thromb Thrombolysis41, 671–677 (2016). https://doi.org/10.1007/s11239-015-1298-z
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