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von Willebrand factor in experimental malaria‐associated acute respiratory distress syndrome
Author(s) -
Kraisin Sirima,
Verhenne Sebastien,
Pham ThaoThy,
Martinod Kimberly,
Tersteeg Claudia,
Vandeputte Nele,
Deckmyn Hans,
Vanhoorelbeke Karen,
Van den Steen Philippe E.,
De Meyer Simon F.
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14485
Subject(s) - von willebrand factor , ards , adamts13 , medicine , plasmodium berghei , immunology , pathogenesis , lung , malaria , platelet
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 NK 65‐E ( Pb NK 65) 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 ADAMTS 13 activity levels were reduced in experimental MA ‐ ARDS . ADAMTS 13‐ 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 NK 65 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 NK 65‐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 NK 65‐infected Vwf −/− mice. VWF deficiency is associated with early reticulocytosis following Pb NK 65 infection, which potentially explains the increase in parasite load.