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Coagulation system activation and increase of D-dimer levels in peripheral arterial occlusive disease
M De Buyzere1, J Philippé, D Duprez
1Department of Cardiology and Angiology, University Hospital, Gent, Belgium.
Insights
Peripheral arterial occlusive disease (PAOD) at stage II shows baseline clotting cascade activation, indicated by elevated prothrombin fragment (F1+2) and thrombin-antithrombin III complexes (TAT). Fibrinolysis is also activated, with increased D-dimer levels.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Biochemistry
Background:
- Peripheral arterial occlusive disease (PAOD) affects circulation, potentially involving coagulation and fibrinolysis.
- Stage II PAOD, characterized by intermittent claudication, warrants investigation into underlying hemostatic changes.
Purpose of the Study:
- To investigate coagulation system activation and basal fibrinolysis in stage II PAOD patients.
- To assess the impact of a standard treadmill test on these parameters.
Main Methods:
- Evaluated prothrombin fragment (F1+2), thrombin-antithrombin III complexes (TAT), and D-dimer concentrations in 34 PAOD patients and controls.
- Measurements were taken before and after a standardized treadmill exercise test.
Main Results:
- PAOD patients exhibited significantly higher basal levels of F1+2 and TAT compared to controls, indicating baseline clotting activation.
- Basal D-dimer levels were significantly elevated in PAOD patients, suggesting secondary activation of fibrinolysis.
- Treadmill exercise did not significantly alter these coagulation or fibrinolysis parameters.
- Walking distance correlated with ankle-brachial systolic blood pressure ratio and inversely with D-dimer levels.
Conclusions:
- Stage II PAOD is characterized by baseline activation of the clotting cascade and secondary activation of the fibrinolytic system.
- Elevated urokinase-type plasminogen activator (u-PA) antigen levels contribute to increased D-dimers in PAOD.
- Standard treadmill exercise does not further activate these hemostatic pathways in stage II PAOD.
Abstract:
The aim of the present study was to document coagulation system activation and basal fibrinolysis in peripheral arterial occlusive disease (PAOD) at stage II of Fontaine's classification. In 34 patients, prothrombin fragment (F1 + 2), thrombin-antithrombin III complexes (TAT), and D-dimer concentrations were evaluated before and after a standard treadmill test. Basal levels in PAOD of F1 + 2 (1.25 +/- 0.19 nmol/liter) and of TAT (3.34 +/- 0.35 micrograms/liter) were significantly increased compared to those obtained in age- and sex-matched healthy controls (0.68 +/- 0.06 nmol/liter and 2.30 +/- 0.33 micrograms/liter, respectively), showing baseline activation of the clotting cascade. A secondary activation of the fibrinolytic system was evidenced by the highly significant increase of basal D-dimers (719 +/- 99 ng/dl in PAOD vs. 229 +/- 37 ng/dl in controls). Treadmill exercise failed to increase the study parameters significantly further. Walking distance (583 +/- 40 m) was correlated with the preexercise ankle to brachial systolic blood pressure ratio (r = 0.485, P < 0.005) and inversely with the level of D-dimers (r = -0.425, P < 0.02). Under baseline conditions, the latter parameter was correlated as well with the antigen concentration of urokinase-type plasminogen activator (u-PA; r = 0.503, P < 0.002). These results indicate that stage II PAOD is characterized by an activation of the clotting cascade in baseline conditions evidenced by increased F1 + 2 and TAT. A secondary activation of the fibrinolytic system with increased u-PA antigen levels accounts for the elevated D-dimers. Treadmill exercise was unable to increase these parameters further.