1921
Volume 80, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF multimers (UL-VWF) in plasma. We studied VWF release and proteolysis in patients with symptomatic or malaria on the Indonesian island Sumba. Malaria patients had significantly lower platelet counts and higher VWF concentrations and VWF activation factors than healthy hospital staff controls. The latter indicates that a higher amount of circulating VWF was in a conformation enabling spontaneous platelet binding. In addition, ADAMTS13 activity and antigen levels were reduced in both malaria groups, and this was associated with the appearance of UL-VWF. The mechanism behind this reduction and the role in malaria pathogenesis needs to be further elucidated. In malaria, endothelial cell activation with increased circulating amounts of active and ultra-large VWF, together with reduced VWF inactivation by ADAMTS13, may result in intravascular platelet aggregation, thrombocytopenia, and microvascular disease.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2009.80.492
2009-03-01
2017-11-19
Loading full text...

Full text loading...

/deliver/fulltext/14761645/80/3/0800492.html?itemId=/content/journals/10.4269/ajtmh.2009.80.492&mimeType=html&fmt=ahah

References

  1. Erhart LM, Yingyuen K, Chuanak N, Buathong N, Laoboonchai A, Miller RS, Meshnick SR, Gasser RA Jr, Wongsrichanalai C, 2004. Hematologic and clinical indices of malaria in a semi-immune population of western Thailand. Am J Trop Med Hyg 70 : 8–14.
  2. Hollestelle MJ, Donkor C, Mantey EA, Chakravorty SJ, Craig A, Akoto AO, O’Donnell J, van Mourik JA, Bunn J, 2006. von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation. Br J Haematol 133 : 562–569.
  3. Wassmer SC, Lepolard C, Traore B, Pouvelle B, Gysin J, Grau GE, 2004. Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J Infect Dis 189 : 180–189.
  4. Wassmer SC, Combes V, Candal FJ, Juhan-Vague I, Grau GE, 2006. Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infect Immun 74 : 645–653.
  5. de Mast Q, Groot E, Lenting PJ, de Groot PG, McCall M, Sauerwein RW, Fijnheer R, van der Ven AJ, 2007. Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis 196 : 622–628.
  6. Hulstein JJ, de Groot PG, Silence K, Veyradier A, Fijnheer R, Lenting PJ, 2005. A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B. Blood 106 : 3035–3042.
  7. Dong JF, Moake JL, Nolasco L, Bernardo A, Arceneaux W, Shrimpton CN, Schade AJ, McIntire LV, Fujikawa K, Lopez JA, 2002. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 100 : 4033–4039.
  8. Moake JL, 2004. von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura. Semin Hematol 41 : 4–14.
  9. Franchini M, Montagnana M, Targher G, Lippi G, 2007. Reduced von Willebrand factor-cleaving protease levels in secondary thrombotic microangiopathies and other diseases. Semin Thromb Hemost 33 : 787–797.
  10. Nguyen TC, Liu A, Liu L, Ball C, Choi H, May WS, Aboulfatova K, Bergeron AL, Dong JF, 2007. Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. Haematologica 92 : 121–124.
  11. Ono T, Mimuro J, Madoiwa S, Soejima K, Kashiwakura Y, Ishiwata A, Takano K, Ohmori T, Sakata Y, 2006. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood 107 : 528–534.
  12. Kokame K, Matsumoto M, Soejima K, Yagi H, Ishizashi H, Funato M, Tamai H, Konno M, Kamide K, Kawano Y, Miyata T, Fujimura Y, 2002. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci USA 99 : 11902–11907.
  13. Ruan C, Dai L, Su J, Wang Z, Ruan C, 2004. The frequency of P475S polymorphism in von Willebrand factor-cleaving protease in the Chinese population and its relevance to arterial thrombotic disorders. Thromb Haemost 91 : 1257–1258.
  14. Bongers TN, De Maat MP, Dippel DW, Uitterlinden AG, Leebeek FW, 2005. Absence of Pro475Ser polymorphism in ADAMTS-13 in Caucasians. J Thromb Haemost 3 : 805.
  15. Rodriguez-Morales AJ, Sanchez E, Vargas M, Piccolo C, Colina R, Arria M, Franco-Paredes C, 2005. Occurrence of thrombocytopenia in Plasmodium vivax malaria. Clin Infect Dis 41 : 130–131.
  16. Genton B, D’Acremont V, Rare L, Baea K, Reeder JC, Alpers MP, Muller I, 2008. Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med 5 : e127.
  17. Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, Lampah DA, Price RN, 2008. Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med 5 : e128.
  18. Baird JK, 2007. Neglect of Plasmodium vivax malaria. Trends Parasitol 23 : 533–539.
  19. Syafruddin D, Asih PB, Coutrier FN, Trianty L, Noviyanti R, Luase Y, Sumarto W, Caley M, van der Ven AJ, Sauerwein RW, 2006. Malaria in Wanokaka and Loli sub-districts, West Sumba District, East Nusa Tenggara Province, Indonesia. Am J Trop Med Hyg 74 : 733–737.
  20. Romijn RA, Westein E, Bouma B, Schiphorst ME, Sixma JJ, Lenting PJ, Huizinga EG, 2003. Mapping the collagen-binding site in the von Willebrand factor-A3 domain. J Biol Chem 278 : 15035–15039.
  21. Raines G, Aumann H, Sykes S, Street A, 1990. Multimeric analysis of von Willebrand factor by molecular sieving electrophoresis in sodium dodecyl sulphate agarose gel. Thromb Res 60 : 201–212.
  22. Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T, 2005. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 129 : 93–100.
  23. van der Plas RM, Schiphorst ME, Huizinga EG, Hene RJ, Verdonck LF, Sixma JJ, Fijnheer R, 1999. von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura. Blood 93 : 3798–3802.
  24. van Rijn BB, Roest M, Franx A, Bruinse HW, Voorbij HA, 2004. Single step high-throughput determination of Toll-like receptor 4 polymorphisms. J Immunol Methods 289 : 81–87.
  25. Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM, 2001. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413 : 488–494.
  26. Jakobsen PH, Morris-Jones S, Ronn A, Hviid L, Theander TG, Elhassan IM, Bygbjerg IC, Greenwood BM, 1994. Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity. Immunology 83 : 665–669.
  27. Spiel AO, Gilbert JC, Jilma B, 2008. von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation 117 : 1449–1459.
  28. Chauhan AK, Walsh MT, Zhu G, Ginsburg D, Wagner DD, Motto DG, 2008. The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis. Blood 111 : 3452–3457.
  29. Martin K, Borgel D, Lerolle N, Feys HB, Trinquart L, Vanhoorelbeke K, Deckmyn H, Legendre P, Diehl JL, Baruch D, 2007. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure. Crit Care Med 35 : 2375–2382.
  30. Nguyen TC, Carcillo JA, 2006. Bench-to-bedside review: thrombocytopenia-associated multiple organ failure–a newly appreciated syndrome in the critically ill. Crit Care 10 : 235.
  31. Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Piera K, Price RN, Duffull SB, Celermajer DS, Anstey NM, 2008. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci USA 105 : 17097–17102.
  32. Daniel-Ribeiro C, Druilhe P, Monjour L, Homberg JC, Gentilini M, 1983. Specificity of auto-antibodies in malaria and the role of polyclonal activation. Trans R Soc Trop Med Hyg 77 : 185–188.
  33. Reiter RA, Knobl P, Varadi K, Turecek PL, 2003. Changes in von Willebrand factor-cleaving protease (ADAMTS13) activity after infusion of desmopressin. Blood 101 : 946–948.
  34. Mannucci PM, Capoferri C, Canciani MT, 2004. Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease. Br J Haematol 126 : 213–218.
  35. Bernardo A, Ball C, Nolasco L, Moake JF, Dong JF, 2004. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood 104 : 100–106.
  36. Chung MC, Popova TG, Jorgensen SC, Dong L, Chandhoke V, Bailey CL, Popov SG, 2008. Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem 283 : 9531–9542.
  37. Studt JD, Hovinga JA, Antoine G, Hermann M, Rieger M, Scheiflinger F, Lammle B, 2005. Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin. Blood 105 : 542–544.
  38. Crawley JT, Lam JK, Rance JB, Mollica LR, O’Donnell JS, Lane DA, 2005. Proteolytic inactivation of ADAMTS13 by thrombin and plasmin. Blood 105 : 1085–1093.
  39. Vreeken J, Cremer-Goote TM, 1978. Haemostatic defect in non-immune patients with falciparum malaria: no evidence of diffuse intravascular coagulation. BMJ 2 : 533–535.
  40. Cao WJ, Niiya M, Zheng XW, Shang DZ, Zheng XL, 2008. Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cells. J Thromb Haemost 6 : 1233–1235.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2009.80.492
Loading
/content/journals/10.4269/ajtmh.2009.80.492
Loading

Data & Media loading...

  • Received : 03 Oct 2008
  • Accepted : 17 Nov 2008

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error