Von Willebrand factor in experimental malaria‐associated acute respiratory distress syndrome. (12th June 2019)

• Record Type: Journal Article
• Authors: Kraisin, Sirima; Verhenne, Sebastien; Pham, Thao‐Thy; Martinod, Kimberly; Tersteeg, Claudia; Vandeputte, Nele; Deckmyn, Hans; Vanhoorelbeke, Karen; Van den Steen, Philippe E.; De Meyer, Simon F.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 17:Number 8(2019)
• Page Start: 1372
• Page End: 1383
• Publication Date: 2019-06-12
• Subjects: malaria -- Plasmodium berghei NK65 -- respiratory distress syndrome -- reticulocytes -- von Willebrand Factor; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.14485
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract: Background: Malaria‐associated acute respiratory distress syndrome (MA‐ARDS) is a lethal complication of severe malaria, characterized by marked pulmonary inflammation. Patient studies have suggested a link between von Willebrand factor (VWF) and malaria severity. Objectives: To investigate the role of VWF in the pathogenesis of experimental MA‐ARDS. Methods: Plasmodium berghei NK65‐E ( Pb NK65) parasites were injected in Vwf +/+ and Vwf −/− mice. Pathological parameters were assessed following infection. Results: In accordance with patients with severe malaria, plasma VWF levels were increased and ADAMTS13 activity levels were reduced in experimental MA‐ARDS. ADAMTS13‐ and plasmin‐independent reductions of high molecular weight VWF multimers were observed at the end stage of disease. Thrombocytopenia was VWF‐independent because it was observed in both Vwf +/+ and Vwf −/− mice. Interestingly, Vwf −/− mice had a shorter survival time compared with Vwf +/+ controls following Pb NK65 infection. Lung edema could not explain this shortened survival because alveolar protein levels in Vwf −/− mice were approximately two times lower than in Vwf +/+ controls. Parasite load, on the other hand, was significantly increased in Vwf −/− mice compared with Vwf +/+ mice in both peripheral blood and lung tissue. In addition, anemia was only observed in Pb NK65‐infected Vwf −/− mice. Of note, Vwf −/− mice presented with two times more reticulocytes, a preferential target of the parasites. Conclusions: This study suggests that parasite load together with malarial anemia, rather than alveolar leakage, might contribute to shortened survival in Pb NK65‐infected Vwf −/− mice. VWF deficiency is associated with early reticulocytosis following Pb NK65 infection, which potentially explains the increase in parasite load.