Effect of experimental endotoxemia on thrombelastography parameters, secondary and tertiary hemostasis in dogs

Abstract

Background

Thrombelastography (TEG) and indicators of secondary and tertiary hemostasis might be altered in dogs with endotoxemia.

Hypothesis

Endotoxemia influences measures of coagulation in dogs.

Animals

Ten healthy cross-bred dogs.

Material and Methods

Prospective laboratory study between controls (n = 5) receiving 0.9% saline IV and the study group (n = 5) treated with low-dose lipopolysaccharide (0.02 mg/kg IV). Physical examination and sampling for measurement of leukocytes, platelets, and coagulation variables were performed at time points 0, 1, 4, and 24 hours. Coagulation variables included kaolin-activated TEG, 1-stage prothrombin time (OSPT), activated partial thromboplastin time (aPTT), fibrinogen, factor VIII, antithrombin, protein C, protein S, activated protein C (APC)-ratio calculated from aPTT with and without presence of APC), and D-Dimers.

Results

Endotoxemia-induced clinical signs included lethargy (n = 5/5), diarrhea (n = 4/5), emesis (n = 4/5), and abdominal pain (2/5). After 1 hour there was severe leukopenia (2.5 +/- 0.7 x 109/L; mean +/- SD, P < .0001) and a 2.2-fold increase in D-Dimers (0.81 +/- 0.64 mg/L, P < .0001). After 4 hours there was hyperthermia (40.3 +/- 0.4 degrees C, P < .0001) and increases in OSPT (10.5 +/- 2.7 seconds, P < .0001), aPTT (16.7 +/- 5.2 seconds, P = 0.002). A significant decrease in fibrinogen (1.5 +/- 1.0 g/L, P = 0.001), protein C (31 +/- 33%, P <.0001), protein S (63 +/- 47%, P < .0001), TEG alpha (58 +/- 19, P = .007), and TEG maximal amplitude (50 +/- 19 mm, P = .003) was seen compared with the controls. APC-ratio rose significantly (2.5 +/- 0.2, P < .0001) without exceeding the reference interval (n = 4/5).

Conclusion and Clinical Importance

D-Dimers are the earliest indicator for endotoxemia-associated coagulation abnormalities followed by decreased protein C concentration. APC-ratio and TEG were not good screening variables.