Pulmonary coagulopathy is intrinsic to
pulmonary injury including
pneumonia.
Anticoagulant strategies could benefit patients with
pneumonia, but systemic administration of
anticoagulant agents may lead to suboptimal local levels and may cause systemic
hemorrhage. We hypothesized nebulization to provide a safer and more effective route for local administration of
anticoagulants. Therefore, we aimed to examine feasibility and safety of nebulization of recombinant human
tissue factor pathway inhibitor (rh-
TFPI) in a well-established rat model of Streptococcus (S.) pneumoniae
pneumonia. Thirty minutes before and every 6 hours after intratracheal instillation of S.
pneumonia causing
pneumonia, rats were subjected to local treatment with rh-
TFPI or placebo, and sacrificed after 42 hours.
Pneumonia was associated with local as well as systemic activation of coagulation. Nebulization of rh-
TFPI resulted in high levels of rh-
TFPI in bronchoalveolar lavage fluid, which was accompanied by an attenuation of pulmonary coagulation. Systemic rh-
TFPI levels remained undetectable, and systemic
TFPI activity and systemic coagulation were not affected. Histopathology revealed no
bleeding in the lungs. We conclude that nebulization of rh-
TFPI seems feasible and safe; local
anticoagulant treatment with rh-
TFPI attenuates pulmonary coagulation, while not affecting systemic coagulation in a rat model of S. pneumoniae
pneumonia.