‘New’ approaches to venous congestion

Keywords::

• leeches
• treatment
• venous congestion
• venous hypertension
• venous insufficiency

Venous outflow is a critical physiologic process that ensures the appropriate oxygenation and precise metabolic balance in the skin and other tissues of the body. Irregularities in intravascular pressures, coagulation, vessel structure and other anatomic changes can obstruct outflow and lead to congestion. Venous congestion, in turn, produces a state of passive hyperemia, where accumulated blood in the venous system leads to cyanosis and ultimately ischemia of the skin and tissues [1]. Venous congestion can be seen acutely, such as after surgery and flap reconstruction, or in more chronic settings.

Venous ulcer disease is often used as a model to study insufficiency in venous outflow. In a competent vascular system in a state of normal venous tension, venous ambulatory pressure is maintained below 30–45 mmHg [2,3]. In the leg, this is accomplished by the gastrocnemius and the soleus muscle pump, which directs venous blood from the deep and superficial venous systems of the calf to the saphenous veins and, ultimately, to the inferior vena cava and heart. The deep and superficial venous systems connect through perforating veins that have valves that close during muscle contraction in order to prevent backflow [4].

However, in the presence of venous congestion, ambulatory pressure rises above 30–45 mmHg. Backflow through incompetent valves ensues, and blood is diverted from the high-pressure, deep venous system to the low-pressure superficial venous system [4]. In this new, hypertensive state, the risk of ulcer formation rises proportionately to the elevation in pressure [3].

Once venous congestion has occurred, a complicated series of molecular and cellular events ensue, resulting in ischemia and/or ulcer formation. The initial proposition that venous blood ‘stasis’ resulted in stagnant anoxia (which in turn led to ischemia and ulcer formation) [5] has largely been dismissed with the observation that oxygen content in venous blood remains at normal levels. Recent investigations have focused on the reduced differential between arteriolar and venular sides of capillaries and the leukocytes trapped in the post-capillary venules as a result of this discrepancy in pressures [6]. These leukocytes, in turn, release proteolytic enzymes and this allows for free radical formation, which results in damaged tissue. Margination of white cells further acts as a diffusion barrier to oxygen and nutrients, contributing to tissue ischemia [6].

Furthermore, venous pooling stretches the inter-endothelial spaces, increasing capillary permeability and enabling edema formation [7]. Fibrinogen leaks into the extravascular space and forms a ‘fibrin cuff’ around dermal blood vessels, further barring diffusion of oxygen and essential nutrients [8]. There is also evidence indicating that TGF-β, a growth factor necessary for wound repair and active in dermal matrix and granulation tissue, is aberrantly distributed and becomes trapped inside this fibrin cuff. These cuffs contain the plasma proteins actin and α2 macroglobulin; α2 macroglobulin is a known scavenger of TGF-β, and thereby further compromises healing mechanisms [9].

Arterio-venous shunting is another phenomenon observed in patients with venous insufficiency. Venous ulcers might fail to heal despite intensive medical management due to the diversion of blood and nutrients away from the wound. Interestingly, embolization of the arterial branches of these shunts has resulted in successful, prolonged healing in these scenarios [10].

The causes of venous congestion are numerous and often multifactorial. Decreased cardiac pump functioning observed in congestive heart failure directly affects venous blood return [6]. Hypercoaguable states, such as Factor V Leiden mutations and protein C and S deficiencies, can predispose venous thrombosis formation, and thus directly obstruct venous outflow [11]. Increased blood viscosity seen in patients with sickle cell anemia, cryoglobulinemia and certain cancers, for example, can lead to congested blood flow [12–14, 101]. Diabetes can affect the structural integrity of the valves and vasculature, while also contributing to other comorbidities. Atherosclerotic disease precipitates red blood cell adherence, leading to turbulent flow and impaired vascular collateralization [15]. Obesity places increased external pressures on the vessels. Varicosity formation from hormonal, congenital and traumatic causes can increase vessel tortuosity, and hence complicate venous return [16]. Valves appear to naturally lose some elasticity over time, while arthritis, neuromuscular disease and trauma may compromise ambulation, and hence diminish calf-muscle pump activity [17]. The list goes on.

In the surgical setting, the incision of tissue can directly damage venous systems, resulting in fewer functioning vessels to accommodate blood flow. This is particularly evident when skin and tissue flaps are employed for reconstructive purposes [16]. Surgical manipulation and the tension associated with suturing and wound closures places additional stress on the remaining viable veins, putting the tissue at risk for ischemia.

Traditional therapies for venous congestion have focused on decreasing ambulatory pressures by employing different forms of compression garments, physiotherapy and exercise to strengthen the calf-muscle pump. Stabilizing venous ambulatory pressures is one of the cornerstones of management in venous ulcer disease. These approaches assist in the physical removal of congested blood and aid in restoring venous outflow.

These measures are often combined with systemic therapies geared at alleviating venous obstruction, but also improving oxygenation and diffusion to the compromised tissues. For example, acetylsalicylic acid has been employed for its antithrombotic and anti-inflammatory affects and has been shown to aid in venous ulcer healing [6]. Anticoagulation with heparin, warfarin, clopidogrel bisulfate and others are employed to prevent and treat coagulopathies and venous thrombosis. Pentoxifylline has been shown to decrease white blood cell adhesion, blood viscosity and platelet aggregation [18]. It has been used postoperatively to salvage ischemic flaps, promote healing of venous ulcers and as an adjunct to venous compression therapy [6,19,20]. Sclerotherapy [21], ambulatory phlebectomy, endovenous ablation, ligation and vein stripping have been used to treat individual superficial and perforating veins that are incompetent [22]. Hyperbaric oxygen therapy has been used to aid in oxygen diffusion, particularly in patients with diabetic foot ulcers [23]. Similarly, newer ‘biologic’ dressings incorporate cellular and molecular materials, such as fibroblasts, collagen and growth factors, to replace sequestered or deficient elements required in wound healing [24].

Leech therapy is an ancient treatment that is being re-evaluated in modern times for its effectiveness in the treatment of venous congestion. Leech saliva possesses a number of components with anticoagulant properties, including hirudin, a potent antiprotease that directly inhibits thrombin activity and the conversion of fibrinogen to fibrin. Other components of the saliva have also been noted to possess fibrinolytic properties [25]. This, combined with the annelid’s ability to physically remove blood and fluid that contributes to venous congestion by sucking, has made them a novel therapy in a variety of settings.

In fact, leech therapy is frequently used to salvage amputated digits and free and pedicle tissue flaps that are compromised by venous congestion after reconstructive surgery [26,27]. By providing drainage for congested blood, leeches increase perfusion until proper venous outflow is established [27]. Leeches have also been used to decrease leg pain and discoloration and improve mobility and circulation in patients with post-thrombotic syndrome [25]. In disseminated intravascular coagulation and purpura fulminans, the application of leeches has been shown to decrease the extent of necrosis in affected tissues [25].

Many are hesitant and even cautious about leech therapy, particularly when one considers the increased risk of infection from Aeromonas hydrophila, a gram-negative bacterium that lives in the animal’s gut. However, similar risks could occur with catheters and other man-made devices that are easily colonized by bacterial agents. To prevent such adverse events, concurrent antibiotics are typically administered with leech therapy.

A drop in hematocrit is somewhat more worrisome and can be significant enough to warrant transfusion after leech therapy has been initiated. Physicians utilizing this approach should be prudent to check serial complete blood counts in patients undergoing therapy [27].

Venous insufficiency and its clinical manifestations remains a significant problem in a large spectrum of diseases. For example, in venous ulcer disease, the prevalence of chronic venous insufficiency has been estimated to be up to 17% in men and 40% in women, with annual impacts on UK healthcare costs of approximately GB£400 million (≈US$800 million) [4,28]. With further research and better understanding of the underlying pathologic mechanisms, newer targeted therapies will be discovered. Until that time, novel uses of current and older modalities can be used in the treatment of this condition and its sequelae.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.