**5. Treatment of the PTS**

Once established, PTS, especially when complicated by leg ulceration, is a significant cause of disability with a considerable economic burden for both patients and the health care

The Post Thrombotic Syndrome 149

Surgery is often advocated when severe clinical manifestations (e.g. ulcer) cannot be managed by conservative treatment: various strategies are available, among whom subfascial perforator ligation and valvuloplasty appear to be the most promising (86). A more recent trial on subfascial endoscopic perforator surgery plus correction of superficial venous reflux indicates that, although effective in improving symptoms and ulcer healing in patients with primary venous insufficiency, this procedure is not as effective in patients with PTS (87). Similarly, deep (femoral-popliteal) valve reconstruction surgery performed after unsuccessful endoscopic perforator surgery, and correction of superficial venous reflux, yields significantly better results in patients with primary venous insufficiency than in patients with PTS (88).

Thrombolysis has been traditionally advocated as an alternative strategy to heparins for the initial treatment of DVT, based on the assumption that early vein recanalization will result in a more favorable long-term outcome. This assumption is in agreement with the findings from several recent studies, which have identified that proximal location of the initial thrombosis is among the strongest predictors of PTS development (33,38,60), especially when the thrombus involves the ilio-femoral segments (39). Consistent with this assumption is the demonstration that post-thrombotic complications develop predominantly in those patients in whom the initial complaints tend to persist (39). Both the intravenous infusion of thrombolytic drugs and the use of catheter-directed thrombolysis are likely to result in a higher frequency of early vein patency as compared to heparin (89-92). However, whether these therapeutic approaches improve the long-term patients' outcome as well is controversial, as there is data in favour (93-96) and against (97,98) this possibility. In addition, the use of either intravenous or catheter-directed thrombolysis is associated with a higher risk of complications compared with treatment with anticoagulants alone (90,100). Thus, the routine use of early thrombolytic therapy for the prevention of long-term sequelae of DVT does not seem to be currently justified, but is the subject of ongoing multicenter

In order to assess the influence of immediate multilayer compression bandages before application of elastic stockings in the acute phase of DVT on development of the PTS, 69 patients with acute symptomatic DVT were recently randomized to immediate bandaging or no bandaging (36). While bandaging resulted in a considerable improvement of clinical symptoms and decrease of leg circumference in the first week of treatment, no difference in the development of late sequelae was observed between the two groups after one year. Thus, the early application of bandages in patients with DVT is unlikely to improve the

Elastic compression stockings have long been utilized for the prevention of the PTS in patients with acute DVT (72). However, their efficacy had not been systematically

**5.2 Surgical treatment** 

**6. Prevention of the PTS** 

randomized trials (100).

long-term patients' outcome.

**6.3 Elastic compression stockings** 

investigated until a few years ago.

**6.1 Initial treatment of DVT with thrombolytic drugs** 

**6.2 Compression bandaging in the acute phase of DVT** 

system (1,2). The management of this condition is demanding and oftentimes frustrating. Several treatment strategies, both conservative and surgical, have been tested, especially aimed at ulcer healing.

### **5.1 Conservative treatment**

Compression therapy, either obtained with short stretch bandages, adhesive bandages, multiple layer bandages (with orthopedic wool plus compressive layers), stockings or zinc bandages, and frequent leg elevation are the cornerstones of the conservative management of venous ulcer (67). Irrespective of the choice, effective compression therapy is obtained with implements exerting a 35 to 40 mm Hg pressure at the ankle (68). Greater benefits (higher and faster healing rates, and low recurrence rates) are to be expected if compliance with compression therapy is monitored through ambulatory care programs, and if patients are encouraged to take regular exercise and to elevate the extremities while resting (69-71). According to the results of a survey conducted among Canadian physicians and patients, most patients with DVT reported being willing to comply with elastic stockings therapy and found them useful (72), although their use neither improves leg symptoms and signs during exercise nor increases exercise capacity (73).

In a randomized clinical trial conducted in a small number of patients with severe PTS, the adoption of cycles of intermittent pneumatic compression was found to reduce both intractable edema and leg swelling (74). In another randomized trial, a novel lower-limb venous-return assist device (VENOPTS) was found to considerably improve the clinical manifestations of severe PTS both alone and in combination with compression stockings (75). Finally, in a recent randomized clinical trial patients with PTS were found to benefit from an exercise training (a six-month trainer-supervised program that included aerobic, leg stretching and strengthening components) to a greater extent than those who had conventional treatment alone both in terms of severity of complaints and improvement in quality of life (76).

In addition to compressive therapy, a number of active compounds have been evaluated in a series of small randomized trials for the healing of venous ulcers. Among these oxpentifylline (77), aspirin (78), intravenous prostaglandin E1 (79), sulphydril-containing agents (DL-cysteine or DL-methionine) (80), radical scavengers (allopurinol or dimethyl sulfoxide) (81), and sulodexide (82) significantly improved the ulcer-healing rate.

With regards to other manifestations of the PTS, two small randomized trials demonstrated some beneficial effect of an anabolic steroid (stanozolol) plus elastic stockings on lipodermatosclerosis (83), and that of 0-(-hydroxyethyl)-rutosides on edema and several milder PTS symptoms (84), respectively.

In a recent clinical trial, we evaluated the efficacy of elastic compression stockings, hydroxyethylrutosides or both for the treatment of PTS (85). In 120 consecutive patients with PTS who were randomized to receive below-knee elastic stockings (30-40 mm Hg at the ankle), oral administration of hydroxyethylrutosides (1000 mg b.i.d.) or both for one year, an improvement of PTS manifestations was observed in similar proportions of patients in each study group. According to these results, elastic stockings and hydroxyethylrutosides seem equally effective in patients with the PTS. The combination of the two remedies does not seem to improve the results obtained by each strategy alone.

### **5.2 Surgical treatment**

148 Deep Vein Thrombosis

system (1,2). The management of this condition is demanding and oftentimes frustrating. Several treatment strategies, both conservative and surgical, have been tested, especially

Compression therapy, either obtained with short stretch bandages, adhesive bandages, multiple layer bandages (with orthopedic wool plus compressive layers), stockings or zinc bandages, and frequent leg elevation are the cornerstones of the conservative management of venous ulcer (67). Irrespective of the choice, effective compression therapy is obtained with implements exerting a 35 to 40 mm Hg pressure at the ankle (68). Greater benefits (higher and faster healing rates, and low recurrence rates) are to be expected if compliance with compression therapy is monitored through ambulatory care programs, and if patients are encouraged to take regular exercise and to elevate the extremities while resting (69-71). According to the results of a survey conducted among Canadian physicians and patients, most patients with DVT reported being willing to comply with elastic stockings therapy and found them useful (72), although their use neither improves leg symptoms and signs during

In a randomized clinical trial conducted in a small number of patients with severe PTS, the adoption of cycles of intermittent pneumatic compression was found to reduce both intractable edema and leg swelling (74). In another randomized trial, a novel lower-limb venous-return assist device (VENOPTS) was found to considerably improve the clinical manifestations of severe PTS both alone and in combination with compression stockings (75). Finally, in a recent randomized clinical trial patients with PTS were found to benefit from an exercise training (a six-month trainer-supervised program that included aerobic, leg stretching and strengthening components) to a greater extent than those who had conventional treatment alone both in terms of severity of complaints and improvement in

In addition to compressive therapy, a number of active compounds have been evaluated in a series of small randomized trials for the healing of venous ulcers. Among these oxpentifylline (77), aspirin (78), intravenous prostaglandin E1 (79), sulphydril-containing agents (DL-cysteine or DL-methionine) (80), radical scavengers (allopurinol or dimethyl

With regards to other manifestations of the PTS, two small randomized trials demonstrated some beneficial effect of an anabolic steroid (stanozolol) plus elastic stockings on lipodermatosclerosis (83), and that of 0-(-hydroxyethyl)-rutosides on edema and several

In a recent clinical trial, we evaluated the efficacy of elastic compression stockings, hydroxyethylrutosides or both for the treatment of PTS (85). In 120 consecutive patients with PTS who were randomized to receive below-knee elastic stockings (30-40 mm Hg at the ankle), oral administration of hydroxyethylrutosides (1000 mg b.i.d.) or both for one year, an improvement of PTS manifestations was observed in similar proportions of patients in each study group. According to these results, elastic stockings and hydroxyethylrutosides seem equally effective in patients with the PTS. The combination of the two remedies does not

sulfoxide) (81), and sulodexide (82) significantly improved the ulcer-healing rate.

aimed at ulcer healing.

quality of life (76).

**5.1 Conservative treatment** 

exercise nor increases exercise capacity (73).

milder PTS symptoms (84), respectively.

seem to improve the results obtained by each strategy alone.

Surgery is often advocated when severe clinical manifestations (e.g. ulcer) cannot be managed by conservative treatment: various strategies are available, among whom subfascial perforator ligation and valvuloplasty appear to be the most promising (86). A more recent trial on subfascial endoscopic perforator surgery plus correction of superficial venous reflux indicates that, although effective in improving symptoms and ulcer healing in patients with primary venous insufficiency, this procedure is not as effective in patients with PTS (87). Similarly, deep (femoral-popliteal) valve reconstruction surgery performed after unsuccessful endoscopic perforator surgery, and correction of superficial venous reflux, yields significantly better results in patients with primary venous insufficiency than in patients with PTS (88).
