Investigations determined the changes in the hemostatic and fibrinolytic systems of C3H/HeN mice after infection with Rickettsia conorii, a model for Rocky Mountain Spotted Fever. Animals, treated with either a sublethal or lethal inoculum of R. conorii, were sacrificed at prescribed periods of time. There were little significant changes from baseline in the PT and APTT in the animals infected with the sublethal dose of R, conorii. Fibrinogen values of all infected mice increased in the first 100 h. Plasma FVIII:C levels increased significantly in the animals infected with the low dose of rickettsiae. Alternatively, there was a correlation between a significant rise in plasma FV:C activity and lethality. FVH:C levels were constants in both groups of animals; FXI:C levels initially dropped in the lethally infected animals, but then recovered. FXII:C, high molecular weight kininogen (HK) procoagulant, and prekallikrein (PK) amidolytic levels were unchanged in the sublethally infected animals. PK levels, but not HK or FXII levels, fell during the fatal course suggesting liver dysfunction. AT values significantly decreased in all animals studied suggesting that there is evidence for thrombin formation. Alternatively, plasminogen amidoiytic levels were insensitive to change in both groups of animals. The most predictive parameters for overall outcome were tPA and PAI-1 values. A fall in tPA activity and a rise in PAI-1 activity highly correlated with a lethal outcome. Alternatively, a rise in tPA and a fall in PAI-1 highly correlated with recovery. These data indicated that infection with R. conorii is associated with primary endothelial cell injury resulting in the most marked changes in the fibrinolytic system. The extent of change was prognostic of outcome. Mouse models of disease are feasible subjects to study the dynamics of hemostatic/ fibrinolytic disorders.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology