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Prior to 1970 the true incidence of postoperative dep vein thrombosis (DVT) was unknown, although surgeons were aware that pulmonary embolism (PE) occurred in 1-4% of patients. The development of the 125I-Fibrinogen test in the 1970s provided a means of screening surgical patients and demonstrated that the incidence of silent DVT varied from 17-47% depending on age, type and duration of operation. Only 4-6% of the patients with DVT developed symptoms. It has now been realised that although symptomatic isolated calf DVT is rarely associated with fatal PE, it produces local damage to venous valves with the development of reflux and post-thrombotic syndrome in 10-23% of patients and has a recurrence rate of 14%. In recent systematic reviews and meta-analyses of patients with symptomatic isolated calf DVT anticoagulation therapy up to 3 months reduces the incidence of recurrent DVT from 7.9% to 1.65% (RR 0.25; 95% CI 0.10-0.67). When anticoagulation period of 3 months was compared with 6 weeks it reduced the incidence of DVT from 14.4% to 4.8% (RR 0.32; 95% CI 0.16-0.64) Current guidelines of European Society of Vascular Surgery are as follows: “For patients with symptomatic calf DVT 3 months therapy is recommended over shorter durations (Class 1, Level A).

The aim of this review is to outline recent randomized controlled trials and strategies that have tested various methods that aim to reduce the risk of recurrent venous thromboembolism (VTE) after the completion of anticoagulant therapy. Aspirin reduced VTE recurrence by approximately 30% (hazard ratio [HR], 0.68; 95% confidence interval [CI] 0.51–0.90) without any increase in bleeding. Dabigatran was effective in reducing VTE (HR, 0.08; 95% CI, 0.02–0.25) but carried a lower risk of major or nonmajor clinically relevant bleeding than warfarin but a higher risk than placebo: 5.3% in the dabigatran group and 1.8% in the placebo group (HR, 2.92; 95% CI, 1.52–5.60). Rivaroxaban was effective in reducing VTE (HR, 0.18; 95% CI, 0.09–0.39) but carried a higher risk of major or nonmajor clinically relevant bleeding than placebo: 6.0% in the rivaroxaban group and 1.2% in the placebo group (HR, 5.19; 95% CI, 2.3–11.7). Apixaban at either treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent VTE from 8.8% in the placebo group to 1.7% in the apixaban group (Relative risk reduction of 81%) (P < 0.001%) without increasing the rate of major bleeding. Sulodexide reduced the risk of recurrence (HR, 0.49; 95% CI 0.27–0.92), without any increase in bleeding risk. Residual thrombus and elevated D-dimer are markers for increased risk of recurrence. Their presence when combined with other risk factors enables one to stratify patients into high, intermediate, or low risk of recurrence of VTE. Other markers enable one to stratify patients into high, intermediate, and low risk for bleeding. On the basis of the balance of risks for recurrence and bleeding, one can advise patients on the need for secondary prevention and the most suitable medication.

The aim of this review is to provide a clear understanding of the pathophysiological mechanisms of chronic venous disease (CVD) at different clinical stages and the possible role of these mechanisms in the development of symptoms in C0s clinical class of the Clinical, Etiologic, Anatomic, and Pathophysiologic classification, which consists of symptomatic patients without any visible or palpable signs of venous disease. The prevalence of C0s class in several epidemiological studies varies between 13% and 23% of the general population. Wall remodeling and valve destruction due to white cell endothelial interaction is the main cause of primary varicose veins, while deep vein thrombosis produces secondary changes leading to the postthrombotic syndrome. The underlying mechanism of the skin changes and ulceration is venous hypertension, which is transmitted to the skin microcirculation. Over the last 10 years, an improved videocapillaroscopic technique, the orthogonal polarization spectral imaging technique demonstrated that quantitative measurements in the skin microcirculation are progressively altered from C1 to C6 patients and that values in CVD patients are significantly different from healthy individuals (P < 0.05): capillary diameter increases and capillary morphology worsens from C2 to C5; diameter of the dermal papilla and diameter of the capillary bulk increase from C3 to C5; and functional capillary density (FCD) decreases from C4 to C5. In addition, significant changes have been shown between C0a and C0s patients despite the presence of normal conventional duplex scans in the latter: a decrease of FCD and an increase in the diameter of the dermal papilla. Functional abnormalities found to be present in C0s patients by recent studies include increased compliance of the venous wall (hypotonic phlebopathy), dilatation of deep veins in the calf producing an abnormally increased venous volume, reduction in emptying of venous reservoir, reduction in the venoarteriolar response on standing, and blood reflux in small venules despite a normal conventional duplex scan. However, most of the studies are small, and their findings need to be confirmed by larger series. It remains to be seen whether functional changes and microcirculatory changes respond to venoactive medications in parallel to the relief of symptoms.