Role of tissue factor in intra-alveolar fibrin deposition and coagulopathy associated with pneumonic pasteurellosis in cattle

Objective - To determine the role of tissue factor (TF) in the coagulation events leading to intra-alveolar fibrin deposition and intravascular thrombosis associated with pneumonic pasteurellosis in cattle. Animals - Healthy 2- to 4-week-old male Holstein calves. Procedures - Blood and bronchoalveolar lavage samples were collected before and at 1, 2, 4, and 6 hours after inoculation of saline solution or Pasteurella haemolytica. Total leukocyte count, platelet count, plasma total protein concentration, prothrombin time, and partial thromboplastin time were measured in blood samples. Total nucleated cell count, total protein concentration, and procoagulant activity were measured in bronchoalveolar lavage samples. Additionally platelet survival in blood, platelet accumulation in affected lung tissue, and gross and microscopic lung lesions were determined. Results - Administration of TF monoclonal antibodies (MAB) TF1-1F7 prevented the decrease in platelet survival and the increase in bronchoalveolar lavage fluid TF-dependent procoagulant activity observed in calves not treated with MAB TF1-1F7 antibody, but did not attenuate the increase in lavage fluid neutrophil numbers and total protein concentration. MAB TF1-1F7 administration reduced the percentage of lung affected by pneumonic lesions from 51.81% to 10.40% and attenuated intra-alveolar deposition of fibrin, neutrophils, and erythrocytes. Conclusion - Intra-alveolar fibrin deposition and activation of coagulation in cattle with pneumonic pasteurellosis is, at least in part, mediated by TF. Clinical Relevance - Treatments that neutralize TF artivity may attenuate lung injury in cattle with pneumonic pasteurellosis.