The natural history of lower-extremity venous disease has received increased attention as our understanding and imaging capabilities of the venous system have developed over the past three decades. The 19th century pathologist Rudolph Virchow was the first to recognize that pulmonary thrombi originate in the extremities; he described this phenomenon by coining the term embolia. Virchow’s early work on understanding the pathogenesis of venous disease led to the classic description of the three factors that predispose to thrombus development (“Virchow’s triad”): stasis, endothelial damage, and hypercoagulability. The surgical management of venous reflux and pulmonary thromboembolism was pioneered by Homan and Trendelenburg, but the emphasis in vascular surgery rapidly shifted to the arterial system with modern advances in treatment of arterial occlusive disease and aneurysms. Although more attention is currently devoted in vascular curricula and training to arterial diseases, the prevalence and disease burden of venous disease are substantial and increasing. Care of chronic venous disease accounts for 2% of total health care costs in the United States and Europe, and the number of working-age patients who have been disabled by chronic venous disease easily exceeds the disability due to arterial disease, which occurs mainly in elderly patients. The natural history of venous disease is highly variable and depends on predisposing factors, as well as medical and surgical interventions. Serial studies of the anatomy and physiology of the venous system, coupled with newer molecular means of diagnosing hereditary thrombophilias (hypercoagulable states), have provided us with a more accurate means of assessing the natural history of these common and disabling conditions.

The disorders of the venous system can be broadly classified into three categories, namely congenital malformations, reflux, and obstruction. Purely venous malformations of the vasculature are relatively unusual, with the most well known of these being Klippel-Trenaunay-Weber syndrome. The Klippel-Trenaunay-Weber anomaly usually affects one lower limb and buttock, and it includes a cutaneous hemangioma (port wine stain); prominent and often atypical varicose veins of the thigh, leg, or hip; and a limb length discrepancy (usually larger but sometimes smaller than the contralateral limb). Evaluation reveals no arterial component to the vascular malformation and perhaps an absent or malformed deep venous system in the involved limb. The natural history of this disorder is generally benign, although misguided surgical removal of the superficial venous varicosities (which may be the only source of venous drainage of the limb) can exacerbate symptoms of chronic venous insufficiency. Venous malformations are discussed more fully in Chapter 76.

The principal venous disorders are venous reflux, venous obstruction, and DVT. Reflux can be due to primary valve dysfunction that is thought to be due to two underlying and interrelated causes. The first is familial valve dysfunction in the superficial veins, which presents as prominent varicose veins and obvious superficial venous reflux in young patients with a frequent family history of similar disorders. The second cause is the gradual rise in the incidence of venous reflux with increasing age. Conditions that can accelerate or accentuate either familial reflux or the ageassociated venous reflux are pregnancy, prolonged standing, and any interval episodes of superficial or deep venous thrombosis (DVT) (discussed below). Clearly an individual’s predisposition to venous valve failure is a critical underlying factor in the ultimate development of symptomatic venous reflux, as the majority of individuals who bear children or engage in lifelong standing occupations never develop symptomatic venous reflux.

Large-scale screening of the population for venous symptoms and reflux demonstrates that the age-adjusted prevalence of chronic venous insufficiency is 9.4% in men and 6.6% in women. There is a strong association between symptoms of chronic venous insufficiency and reflux in both the superficial and deep venous systems. One-third of individuals with symptoms of chronic venous insufficiency have reflux confined to the superficial venous system.

The anatomic patterns of superficial venous reflux are quite heterogeneous, with the majority of patients having reflux primarily in the greater saphenous vein. Patients, however, can also have reflux predominantly in the lesser (short) saphenous vein, and 4% to 5% of patients with venous ulceration will have isolated lesser saphenous reflux as the cause. In patients with lesser saphenous reflux, one-half will also have reflux at the saphenofemoral junction (greater saphenous reflux), and one-quarter will have reflux into the lesser saphenous from an incompetent perforator vein.

What is the natural history of patients with primary venous reflux? Although long-term natural history studies in this specific population are not available, two observations lend insight to this issue. The first observation is that half of patients with venous ulceration have reflux confined to the superficial system. Thus while not all patients with superficial reflux will progress to ulceration, there exists a subset of patients who at one point had presumably milder superficial reflux that progressed to
eventual ulceration. The second observation is that superficial reflux leads to reversible reflux of the deep venous system. Deep venous reflux occurs in approximately 25% of patients with superficial venous reflux, and it is abolished in 30% to 90% of patients following treatment of the superficial reflux.

This finding has led to the overload theory of venous recirculation as a potential explanation for the spread of venous reflux from the superficial system to the deep system. Serial duplex studies indicate that frequently venous reflux starts in the superficial system and then spreads to the deep system. Within the superficial system, reflux begins in axial segments away from the junctions with the deep system. Blood flows down the limb via refluxing superficial veins and ultimately flows to the deep system via perforator veins, and it can then re-enter the superficial system at the saphenofemoral or saphenopopliteal junction and thus recirculate in the limb. This increased blood volume distends and increases the diameter of the deep veins, which causes the valve leaflets to lose apposition and results in secondary deep venous reflux. Venous reflux in the proximal deep veins, i.e., the common femoral vein, could then cause progressive reflux in more distal segments by increases in vein diameter sequentially in distal segments. Compared to an intrinsic valvular defect in the vein, this secondary deep venous reflux should, in theory, be corrected by elimination of the superficial reflux, which would reduce the volume in the deep system. Correction of deep venous reflux by eliminating superficial reflux supports this theory of progression of superficial reflux to deep venous reflux.

A poorly understood aspect of venous reflux is the widely varying manifestations of a common hemodynamic problem, namely increased ambulatory pressure in the superficial venous system. Some patients will present with large varicose veins and associated pain, whereas others may have primarily spider veins or present simply with a nonhealing malleolar ulcer without significant varicosities or antecedent symptoms. Similarly, there is considerable variability in the degree to which each of the manifestations of superficial venous hypertension causes discomfort or pain. Patients with venous reflux may have enormous but essentially asymptomatic varicose veins with no associated symptoms, whereas other patients may have considerable pain with minor varicosities or only spider veins. Bleeding from varicosities often occurs in patients with relatively small varicose veins, whereas others with very large varicosities often will be without complaint. This wide spectrum of clinical manifestations of venous reflux also does not fall into a clear pattern of progression. Patients who do not undergo treatment for large varicosities may never progress to venous ulceration, and the size and number of varicosities or other superficial skin lesions (i.e., telangiectasias, or spider veins) may remain constant over decades. Thus the natural history of varicose veins, or the simple presence of superficial venous reflux, does not generally mandate intervention in the absence of significant attributable symptoms.

Venous thrombosis is the other major cause of venous disease in adults, and unlike venous reflux, it is a significant cause of mortality as well as morbidity. Thrombosis confined to the superficial veins is described as thrombophlebitis, a misleading term that is used to describe both noninfected thrombosis and inflammation of the superficial veins, as well as purulent infections of the veins and thrombus (sometimes referred to as septic thrombophlebitis). Risk factors for both septic and aseptic phlebitis include mechanical trauma from needle or plastic cannulae, indwelling catheters in the veins of the upper extremity or chest, chemical injury from medication infusion, varicose veins (in the lower extremities), hormone replacement therapy, thromboangiitis obliterans (Buerger disease), and polyarteritis nodosa. A specific recurrent and migratory subtype of superficial thrombophlebitis is the paraneoplastic phenomenon referred to as Trousseau syndrome. In cases of septic thrombophlebitis, the most common responsible species are the epidermal flora S. epidermidis and S. aureus, though more unusual bacteria and even fungi may be to blame in immunocompromised patients.