Does coagulopathy contribute to the outcome of invasive pulmonary aspergillosis?

Invasive pulmonary aspergillosis is a deadly disease caused by the mold Aspergillus. As the mold grows in the lungs, fungal hyphae penetrate the epithelium, resulting in lung hemorrhage. We previously reported that extracellular heme worsens the outcome of the infection. We hypothesize that hemostasis is protective in invasive aspergillosis. Methods: C57Bl/6J mice were partially neutrophil-depleted and challenged with Aspergillus conidia. We performed serial thromboelastography on the blood of infected mice and control mice, sampled the alveolar lumen by bronchoalveolar lavage (BAL. We also performed ELISAs for coagulation factor Xa and Thrombin-antithrombin complex on BAL. We used mathematical modeling to map coagulation factors to thromboelastography curves and predict coagulation factors that explain observed TEG patterns. In some experiments, infected mice were treated with clinical drugs that inhibit factor Xa (apixaban) and prevent fibrinolysis (tranexamic acid). Results: Infected mice had higher levels of factor Xa and thrombin-antithrombin complex in BAL, and higher maximum amplitudes in thromboelastography compared to uninfected mice, indicating appropriate activation of the coagulation. Unexpectedly, infected animals had an elongated time to clot on thromboelastography. Our model predicted a potential depletion of factors X or VII. We found a partial depletion of factor VII but not factor X in the blood. Treatment with apixaban increased fungal burden. Treatment with tranexamic acid resulted in a pronounced reduction in fungal burden in female mice but had no effect on male mice. Conclusions: Our preliminary studies suggest that coagulopathy is an important component of invasive aspergillosis and that treatment with anticoagulants during infection might lead to worse outcomes in mice. Treatment with an anti-fibrinolytic agent led to a lowered fungal burden in female mice, and agents that aid in clot formation might improve outcomes in mice.

Does coagulopathy contribute to the outcome of invasive pulmonary aspergillosis?

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"Does coagulopathy contribute to the outcome of invasive pulmonary aspergillosis?"

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