Coagulation system activation and increase of D‐dimer levels in peripheral arterial occlusive disease

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.

The effect of exercise on coagulation and fibrinolysis factors in patients with peripheral arterial disease

“…12 In most studies, baseline D-dimer levels are reported to be higher in claudicants compared to healthy controls. 2,16,19,20 D-dimer levels significantly increase after exercise compared to the respective levels of healthy controls, 2,16,19,20 and it appears to persist up to 1 h postexercise. 2 This increase is not significant when compared to the baseline values.…”

“…9 The other markers of coagulation activity, PF1 þ 2, are reported by two studies to be at a higher baseline level compared to controls and this difference between claudicants and healthy control persists in the early post-exertion period. 19,20 Only one study did not report any difference between the PF1 þ 2 pre-exertion levels of claudicants and smoking controls, but a significant increase was reported when compared to non-smoking controls. 11 Constans et al take a different approach and compares the immediate post-exertion and the post-resting levels of PF1 þ 2 to the respective baseline, reporting that immediately after exercise there is no significant increase to baseline, but after a period of rest PF1 þ 2 levels rise significantly.…”

“…2,11,16,19,20,25 Three studies found that no significant difference exist between the pre-exercise baseline TAT levels of control groups and claudicants, 2,11,16 while two studies reported that claudicants presented with a higher TAT level at baseline compared to healthy controls. 19,20 These two contradictory reports are supported by similar number of age-matched subjects, therefore no safe conclusion can be drawn from these studies regarding the baseline TAT level in claudicants. On the contrary the majority of studies supports that TAT levels rise significantly immediately after and up to 1 h after exertion when compared to controls but this increase is not significant when compared to baseline.…”

“…On the contrary the majority of studies supports that TAT levels rise significantly immediately after and up to 1 h after exertion when compared to controls but this increase is not significant when compared to baseline. 2,11,16,19,20 According to one of these studies, this post-exercise TAT increase can persist even after 30 min of rest. 16 This rise in post-exertion TAT levels is disputed only by Hobbs et al, who report that TAT levels do not rise significantly even up to three months post-exertion (to a total of 6 months from commencing exercise), but the study method is unique and has not been reproduced-even in a similar fashion-in any other of the series.…”

Thrombin Generation and Atherothrombosis: What Does the Evidence Indicate?

“…Two studies published in 1993 addressed markers of thrombin in patients with PAD, showing a positive association between TAT and PAD65 and elevations of both F1.2 and TAT in patients with PAD, however, not related to severity of atherosclerosis 66. Heinrich et al and van der Bom and colleagues did not find significant associations of F1.2,67 or F1.2 or TAT38 with prevalent PAD, respectively.…”