| First Author | Kraisin S | Year | 2019 |
| Journal | J Thromb Haemost | Volume | 17 |
| Issue | 8 | Pages | 1372-1383 |
| PubMed ID | 31099973 | Mgi Jnum | J:295783 |
| Mgi Id | MGI:6454414 | Doi | 10.1111/jth.14485 |
| Citation | Kraisin S, et al. (2019) von Willebrand factor in experimental malaria-associated acute respiratory distress syndrome. J Thromb Haemost 17(8):1372-1383 |
| abstractText | 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 (PbNK65) 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 PbNK65 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 PbNK65-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 PbNK65-infected Vwf(-/-) mice. VWF deficiency is associated with early reticulocytosis following PbNK65 infection, which potentially explains the increase in parasite load. |
