Related Experiment Videos
The fibrinolytic potential in patients with Cushing's disease: a clue to their hypercoagulable state
G M Patrassi1, M T Sartori, M L Viero
1Institute of Medical Semeiotics, University of Padua Medical School, Italy.
Insights
Patients with Cushing's disease exhibit impaired fibrinolytic activation due to high plasminogen activator inhibitor (PAI) levels, increasing risks for blood clots. This defective fibrinolytic potential contributes to a hypercoagulable state in these patients.
Area of Science:
- Endocrinology
- Hematology
- Thrombosis Research
Background:
- Cushing's disease is associated with a hypercoagulable state.
- The fibrinolytic system's role in Cushing's disease requires further elucidation.
Purpose of the Study:
- To investigate the fibrinolytic potential in patients with Cushing's disease.
- To assess the impact of plasminogen activator inhibitor (PAI) on fibrinolysis in Cushing's disease.
Main Methods:
- Compared coagulation parameters (activated partial thromboplastin time, factor VIII/von Willebrand factor complex) in Cushing's patients and controls.
- Measured levels of plasminogen, tissue plasminogen activator (t-PA) antigen, and PAI activity.
- Utilized a venous occlusion test to evaluate fibrinolytic activation and response.
Main Results:
- Cushing's patients showed elevated t-PA antigen and PAI activity, but similar basal fibrinolytic activity compared to controls.
- Venous occlusion revealed comparable t-PA release but reduced fibrinolytic activity and unchanged PAI levels in Cushing's patients.
- High PAI levels in Cushing's patients inhibited plasminogen activators, impairing fibrinolytic activation.
Conclusions:
- Impaired fibrinolytic activation in Cushing's disease is linked to high PAI levels inhibiting plasminogen activators.
- Defective fibrinolytic potential contributes to the hypercoagulable state in Cushing's disease.
- Elevated pre-operative PAI levels may indicate increased risk for post-surgical thromboembolic complications.
Abstract:
The aim of our study was to determine the fibrinolytic potential in a large group of patients with Cushing's disease. These patients had a significant shortening of the activated partial thromboplastin time and increase in factor VIII/von Willebrand factor complex compared to normal controls. The mean levels of plasminogen, tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity were significantly higher than in normal subjects, whereas the basal fibrinolytic activity was similar to that seen in the control group. In 17 out of 30 Cushing patients and in 17 normal subjects the fibrinolytic potential was determined with the venous occlusion test. In the Cushing group, the release of t-PA antigen after 20 min of venous occlusion was comparable to that observed in the control group. However, Cushing patients showed a lower fibrinolytic activity than normal subjects, since a lesser shortening of the euglobulin lysis time and a non-significant rise of plasminogen activator activity levels were found. Moreover, in these patients the PAI activity values remained unchanged and significantly increased after venous occlusion test also. In conclusion, the impaired fibrinolytic activation seen in Cushing patients after venous occlusion can be explained by the inhibitory effect of the high PAI levels on plasminogen activators. The defective fibrinolytic potential could further contribute to the hypercoagulable state in Cushing's disease. High PAI levels before surgery may represent an additional risk factor for post-surgical thromboembolic complications in Cushing patients.