Biochemical basis for the hypercoagulable state seen in Cushing syndrome; discussion 1006-7.
OBJECTIVE
Cushing syndrome (CS) is associated with a hypercoagulable state that results in a 4-fold increase in the incidence of pulmonary embolism, deep venous thrombosis, and a 4-fold mortality rate compared with the general population. The incidence of CS in humans is approximately 2 to 5 per million per year, whereas in dogs it is much higher. The clinical complications of CS in humans are also manifested in dogs. We used a dog model of CS to better define the biochemical basis for the hypercoagulable state seen in the disease.


METHODS
A consecutive sample of dogs with CS and a cohort of healthy control dogs identified at a "well-dog check" were enrolled. All dogs underwent blood assays to identify the levels of procoagulant factors, natural antithrombotics, and the degree of ongoing activation of the coagulation cascade.


METHODS
University veterinary medical teaching hospital.


RESULTS
A total of 86 dogs were enrolled, 56 with CS and 30 control dogs. Levels of procoagulation factors II, V, VII, IX, X, XII, and fibrinogen were significantly increased in dogs with CS (P<.05). The natural antithrombotic antithrombin was significantly decreased in dogs with CS (P<.02). Thrombin-antithrombin complexes, a marker of subclinical thrombosis, were significantly increased in dogs with CS (P<.05).


CONCLUSIONS
The hypercoagulable state of CS is demonstrated by an increase in thrombin-antithrombin complexes. This hypercoagulable state may be caused in part by (1) an elevation of procoagulant factors, and (2) a decrease in antithrombin. Because of the similar clinical and biochemical changes between dogs with CS and humans, this canine model may be a useful tool for the future study of the hypercoagulable state in CS.
Jacoby
R C
RC
Department of Surgery, University of California-Davis, Medical Center, 2315 Stockton Blvd, Room 4209, Sacramento, CA 95817, USA.
Owings
J T
JT
Ortega
T
T
Gosselin
R
R
Feldman
E C
EC
D000818:Animals; D000990:Antithrombin III; D001779:Blood Coagulation Factors / Q000032:analysis*; D003480:Cushing Syndrome / Q000097:blood* / Q000150:complications; D004285:Dogs; D005340:Fibrinogen / Q000032:analysis; D010447:Peptide Hydrolases / Q000097:blood; D019851:Thrombophilia / Q000097:blood / Q000150:complications*
D001779:Blood Coagulation Factors; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases