Journal of Thrombosis and Thrombolysis

, Volume 41, Issue 4, pp 671–677 | Cite as

The impact of schistosomes and schistosomiasis on murine blood coagulation and fibrinolysis as determined by thromboelastography (TEG)

  • Akram A. Da’dara
  • Armelle M. de Laforcade
  • Patrick J. Skelly


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.


Blood fluke Coagulation Host–parasite interaction Fibrinolysis Thromboelastography 



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.


  1. 1.
    Vennervald BJ, Dunne DW (2004) Morbidity in schistosomiasis: an update. Curr Opin Infect Dis 17:439–447CrossRefPubMedGoogle Scholar
  2. 2.
    King CH, Dangerfield-Cha M (2008) The unacknowledged impact of chronic schistosomiasis. Chronic Illn 4:65–79CrossRefPubMedGoogle Scholar
  3. 3.
    Colley DG, Bustinduy AL, Secor WE, King CH (2014) Human schistosomiasis. Lancet 383:2253–2264CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Keating J, Wilson R, Skelly P (2006) No overt cellular inflammation around intravascular schistosomes in vivo. J Parasitol 92(6):1365–1369CrossRefPubMedGoogle Scholar
  5. 5.
    Wu YP, Lenting PJ, Tielens AG, de Groot PG, van Hellemond JJ (2007) Differential platelet adhesion to distinct life-cycle stages of the parasitic helminth Schistosoma mansoni. J Thromb Haemost 5:2146–2148CrossRefPubMedGoogle Scholar
  6. 6.
    Yeaman M, Bayer A (2007) Antimicrobial host defense. In: Michelson A (ed) Platelets, 2nd edn. Academic Press, Burlington, pp 727–755CrossRefGoogle Scholar
  7. 7.
    Bolliger D, Seeberger MD, Tanaka KA (2012) Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev 26:1–13CrossRefPubMedGoogle Scholar
  8. 8.
    Tucker MS, Karunaratne LB, Lewis FA, Freitas TC, Liang YS. Schistosomiasis. Current protocols in immunology/ed Coligan JE et al. 2013;103:Unit 19 1Google Scholar
  9. 9.
    MacDonald SG, Luddington RJ (2010) Critical factors contributing to the thromboelastography trace. Semin Thromb Hemost 36:712–722CrossRefPubMedGoogle Scholar
  10. 10.
    Leite LA, Pimenta Filho AA, Martins da Fonseca CS, Santana dos Santos B, Ferreira Rde C, Montenegro SM et al (2013) Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis. PLoS Negl Trop Dis 7:e2314CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Omran SA, Amer AM, el-Kaliouby AH, Eldin AA (1991) Study of contact activation in endemic hepatosplenomegaly. Blood Coagul Fibrinolysis 2:659–662CrossRefPubMedGoogle Scholar
  12. 12.
    El-Bassiouni NE, El Bassiouny AE, Hussein NA, El-Sayed HH, Ibrahim IM, Lotfy MG et al (1998) The coagulation profile in hepatosplenic schistosomiasis. Blood Coagul Fibrinolysis 9:189–194CrossRefPubMedGoogle Scholar
  13. 13.
    Souza MR, Toledo CF, Borges DR (2000) Thrombocytemia as a predictor of portal hypertension in schistosomiasis. Dig Dis Sci 45:1964–1970CrossRefPubMedGoogle Scholar
  14. 14.
    Ngaiza JR, Doenhoff MJ (1987) Schistosoma mansoni-induced thrombocytopenia in mice. Trans R Soc Trop Med Hyg 81:655–656CrossRefPubMedGoogle Scholar
  15. 15.
    Vasconcelos EG, Nascimento PS, Meirelles MN, Verjovski-Almeida S, Ferreira ST (1993) Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni. Mol Biochem Parasitol 58:205–214CrossRefPubMedGoogle Scholar
  16. 16.
    Vasconcelos EG, Ferreira ST, Carvalho TM, Souza W, Kettlun AM, Mancilla M et al (1996) Partial purification and immunohistochemical localization of ATP diphosphohydrolase from Schistosoma mansoni. Immunological cross-reactivities with potato apyrase and Toxoplasma gondii nucleoside triphosphate hydrolase. J Biol Chem 271:22139–22145CrossRefPubMedGoogle Scholar
  17. 17.
    Da’dara AA, Bhardwaj R, Ali YBM, Skelly P (2014) Schistosome tegumental ecto-apyrase (SmATPDase1) degrades exogenous pro-inflammatory and pro-thrombotic nucleotides. PeerJ. 2:e316. doi: 10.7717/peerj.316 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Bhardwaj R, Skelly PJ (2009) Purinergic signaling and immune modulation at the schistosome surface? Trends Parasitol 25:256–260CrossRefPubMedGoogle Scholar
  19. 19.
    Lin YL, He S (2006) Sm22.6 antigen is an inhibitor to human thrombin. Mol Biochem Parasitol 147:95–100CrossRefPubMedGoogle Scholar
  20. 20.
    Blanton RE, Licate LS, Aman RA (1994) Characterization of a native and recombinant Schistosoma haematobium serine protease inhibitor gene product. Mol Biochem Parasitol 63:1–11CrossRefPubMedGoogle Scholar
  21. 21.
    Braschi S, Wilson RA (2006) Proteins exposed at the adult schistosome surface revealed by biotinylation. Mol Cell Proteomics 5:347–356CrossRefPubMedGoogle Scholar
  22. 22.
    Braschi S, Curwen RS, Ashton PD, Verjovski-Almeida S, Wilson A (2006) The tegument surface membranes of the human blood parasite Schistosoma mansoni: a proteomic analysis after differential extraction. Proteomics 6:1471–1482CrossRefPubMedGoogle Scholar
  23. 23.
    Braschi S, Borges WC, Wilson RA (2006) Proteomic analysis of the schistosome tegument and its surface membranes. Mem Inst Oswaldo Cruz 101(Suppl 1):205–212CrossRefPubMedGoogle Scholar
  24. 24.
    Robertson NP, Cain GD (1985) Isolation and characterization of glycosaminoglycans from Schistosoma mansoni. Comp Biochem Physiol B 82:299–306PubMedGoogle Scholar
  25. 25.
    Salafsky B, Fusco AC (1987) Schistosoma mansoni: a comparison of secreted vs nonsecreted eicosanoids in developing schistosomulae and adults. Exp Parasitol 64:361–367CrossRefPubMedGoogle Scholar
  26. 26.
    Angeli V, Faveeuw C, Roye O, Fontaine J, Teissier E, Capron A et al (2001) Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J Exp Med 193:1135–1147CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Smith JB, Silver MJ, Ingerman CM, Kocsis JJ (1974) Prostaglandin D2 inhibits the aggregation of human platelets. Thromb Res 5:291–299CrossRefPubMedGoogle Scholar
  28. 28.
    Ramajo-Hernandez A, Perez-Sanchez R, Ramajo-Martin V, Oleaga A (2007) Schistosoma bovis: plasminogen binding in adults and the identification of plasminogen-binding proteins from the worm tegument. Exp Parasitol 115:83–91CrossRefPubMedGoogle Scholar
  29. 29.
    de la Torre-Escudero E, Manzano-Roman R, Perez-Sanchez R, Siles-Lucas M, Oleaga A (2010) Cloning and characterization of a plasminogen-binding surface-associated enolase from Schistosoma bovis. Vet Parasitol 173:76–84CrossRefPubMedGoogle Scholar
  30. 30.
    de la Torre-Escudero E, Manzano-Roman R, Siles-Lucas M, Perez-Sanchez R, Moyano JC, Barrera I et al (2012) Molecular and functional characterization of a Schistosoma bovis annexin: fibrinolytic and anticoagulant activity. Vet Parasitol 184:25–36CrossRefPubMedGoogle Scholar
  31. 31.
    Carvalho WS, Lopes CT, Juliano L, Coelho PM, Cunha-Melo JR, Beraldo WT et al (1998) Purification and partial characterization of kininogenase activity from Schistosoma mansoni adult worms. Parasitology 117(Pt 4):311–319CrossRefPubMedGoogle Scholar
  32. 32.
    Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M et al (2011) New topics in bradykinin research. Allergy 66:1397–1406CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Akram A. Da’dara
    • 1
  • Armelle M. de Laforcade
    • 2
  • Patrick J. Skelly
    • 1
  1. 1.Department of Infectious Disease and Global Health, Molecular Helminthology LaboratoryTufts UniversityNorth GraftonUSA
  2. 2.Department of Clinical Sciences, Cummings School of Veterinary MedicineTufts UniversityNorth GraftonUSA

Personalised recommendations