Elevated plasma von Willebrand factor and propeptide levels in Malawian children with malaria.

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Happy T Phiri ; Daniel J Bridges ; Simon J Glover ; Jan A van Mourik ; Bas de Laat ; Bridon M'baya ; Terrie E Taylor ; Karl B Seydel ; Malcolm E Molyneux ; E Brian Faragher ; Alister G Craig ; James E G Bunn
  • Publisher: Public Library of Science (PLoS)
  • Journal: PLoS ONE, volume 6, issue 11 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: doi: 10.1371/journal.pone.0025626, pmc: PMC3219631
  • Subject: ws_20 | Research Article | Diagnostic Medicine | Pathology | Coagulation disorders | von Willebrand disease | Infectious Diseases | Malaria | wh_20 | Proteins | Plasmodium Falciparum | Ophthalmology | Pediatric Hematology | Neuropathology | Neurology | Public Health | ws_100 | Biology | Plasma Proteins | Tropical Diseases (Non-Neglected) | Biomarkers | Microbiology | Anatomical Pathology | Medicine | Child Health | Pathogenesis | Q | Hematology | R | wh_322 | wh_100 | Biochemistry | Pediatrics | Science | Retinal Disorders | General Pathology
    mesheuropmc: parasitic diseases

Background In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls. Methods and Findings Children with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later. Conclusions In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative ‘cerebral malaria’ cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.
  • References (34)
    34 references, page 1 of 4

    1. Newton CR, Taylor TE, Whitten RO (1998) Pathophysiology of fatal falciparum malaria in African children. Am J Trop Med Hyg 58: 673-83.

    2. Ettling M, Steketee RW, Macheso A, Schultz LJ, Nyasulu Y, et al. (1994) Malaria knowledge, attitudes and practices in Malawi: survey population characteristics. Trop Med Parasitol 45: 57-60.

    3. Sulo J, Chimpeni P, Hatcher J, Kublin JG, Plowe CV, et al. (2002) Chlorproguanil-dapsone versus sulfadoxine-pyrimethamine for sequential episodes of uncomplicated falciparum malaria in Kenya and Malawi: a randomised clinical trial. Lancet 360: 1136-43.

    4. van Mourik JA, Romani de Wit T (2001) Von Willebrand factor propeptide in vascular disorders. Thromb Haemost 86: 164-71.

    5. Rubin DB, Wiener-Kronish JP, Murray JF, Green DR, Turner J, et al. (1990) Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 86: 474-80.

    6. Zeigler ZR, Rosenfeld CS, Andrews DF, 3rd, Nemunaitis J, Raymond JM, et al. (1996) Plasma von Willebrand Factor Antigen (vWF:AG) and thrombomodulin (TM) levels in Adult Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). Am J Hematol 53: 213-20.

    7. Stel HV, Sakariassen KS, de Groot PG, van Mourik JA, Sixma JJ (1985) Von Willebrand factor in the vessel wall mediates platelet adherence. Blood 65: 85-90.

    8. Ruggeri ZM, Ware J (1993) von Willebrand factor. FASEB J 7: 308-16.

    9. Wagner DD, Fay PJ, Sporn LA, Sinha S, Lawrence SO, et al. (1987) Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci U S A 84: 1955-9.

    10. Hannah MJ, Skehel P, Erent M, Knipe L, Ogden D, et al. (2005) Differential kinetics of cell surface loss of von Willebrand factor and its propolypeptide after secretion from Weibel-Palade bodies in living human endothelial cells. J Biol Chem 280: 22827-30.

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