**4. Predictors of PTS development**

Among parameters that have been found to be associated with an increased risk of the PTS are proximal DVT (33,38,39,60), previous ipsilateral DVT (14,16,18,28,29,33,39), older age (29,65), obesity (38,39,65-67), and varicose veins (38). In one investigation the male gender was a predictor of the PTS (33), while in others the opposite was seen (38,39). Finally, whether the carriage of factor V Leiden or the prothrombin mutation are predictors of a lower risk or reduced severity of the PTS is controversial, as there are data in favor (31) and against (38,39) this association.

In order to determine the frequency, time course, and predictors of the PTS after acute DVT, we followed 387 patients for up to two years after an episode of acute symptomatic DVT (39). With the use of the Villalta score, greater postthrombotic severity category at the 1 month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up (1.97, 5.03, and 7.00 increase in Villalta score for mild, moderate, and severe 1 month severity categories, respectively, vs. none). Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein (2.23 increase in score vs. distal venous thrombosis), higher body mass index (0.14 increase in score per kg/m2), previous ipsilateral venous thrombosis (1.78 increase in score), older age (0.30 increase in score per 10-year age increase), and female sex (0.79 increase in score). Accordingly, appropriate strategies aimed at reducing the risk of recurrent DVT, and reducing the body weight in obese patients have the potential to help prevent late postthrombotic sequelae.

Proximal DVT is associated with a higher frequency and more severe PTS than distal DVT. In the abovementioned study, patients with more extensive proximal (femoral or iliac vein) DVT had significantly worse PTS scores at all visits (adjusted average increase of > 2 points on the Villalta scale) than those with distal or popliteal vein DVT (39). Similarly, in another recent prospective study, proximal DVT was found to be associated with a 2-fold increased risk of PTS compared with distal DVT (33). As the rates of PTS in the control arms of trials of compression stockings to prevent PTS in patients with proximal DVT ranged from 40-50%, the rate of PTS after distal DVT is likely to be in the range of 20-25%, however in one study, symptoms of PTS after distal DVT were relatively mild (23).

Finally, an insufficient quality of oral anticoagulant therapy following the acute thrombotic episode has been found to be associated with an increased risk of the PTS (28,65). Accordingly, appropriate attention to the monitoring of oral anticoagulant therapy following the initial thrombotic episode, in terms of both adequate intensity and duration, has the potential to help prevent late post-thrombotic sequelae.
