US Pharm. 2008;33(4):22-30.

Approximately 25 percent of Americans are affected by chronic venous insufficiency.1 Deep vein thrombosis (DVT) is the second most common vascular problem in the United States and affects as many as 600,000 people every year.2 Graduated compression stockings are routinely prescribed for DVT prophylaxis by health care providers in both hospital and community settings.3 Additionally, published clinical-practice guides consider compression bandaging to be the standard of care for treating venous leg ulcers.4 Compression, whether from hosiery or from bandages, reduces venous hypertension by increasing pressure on both superficial veins and deep veins. Some patients refuse to wear compression hosiery or bandages because of limited mobility or dexterity, so that lack of compliance becomes a barrier to prevention. Clinically based evidence lacks uniformity regarding patient compliance with compression therapy and which device should be used to improve adherence. Given the large number of citations offering a broad range of clinical opinions, confusion exists regarding the gold standard for compression therapy. As such, there is wide variation in the prescribing of compression hosiery for venous ulceration, prevention of varicose veins, and DVT prevention. Due to the lack of clear evidence-based guidelines, pharmacists may find themselves at a disadvantage when asked to assist a patient or health care provider in choosing a suitable compression stocking.

The foremost object of this review is to empower the pharmacist with relative knowledge about the purpose of compression hosiery and its function as a preventative tool and treatment modality. To achieve this end, the pharmacist must first understand the anatomy and pathophysiology that can lead to DVT and the development of venous leg ulceration. In addition, the pharmacist must recognize and appreciate the different classes of compression hosiery available for treating venous leg ulcers. Finally, in order to counsel patients about proper use of their compression hosiery, thereby rendering them more likely to comply, the pharmacist must learn the rules of measurement for these durable goods, as well as their utility and how to care for them.

Anatomy and Physiology
Both the anatomy and normal physiology of the venous circulatory system must be understood by the pharmacist so that the purpose and function of compression hosiery can be appreciated. The pressure of the blood entering normally functioning veins is quite low, and the blood has insufficient energy to return to the heart. Therefore, all veins in the lower extremities contain valves that ensure upward flow to the heart (FIGURE 1). Blood is returned to the heart by intrathoracic pressure caused by active respiration that creates a suction effect within the veins. Pressure exerted by a series of pumps found in the foot, calf, and thigh also assist with blood return to the right atrium of the heart.5-7

Adequate venous return from the lower extremity requires an intricate network of superficial veins, deep veins, bicuspid valves, and calf muscles all working together, as illustrated in FIGURE 1.5-7 Deep leg veins have a larger diameter, creating greater pressure, and are connected by perforator veins to the smaller-diameter superficial veins that are under less pressure. These superficial veins are found immediately beneath the skin in subcutaneous fat, whereas deep veins lie beneath the deep fascia of the leg and usually are covered by the muscles of the lower limb. The deep veins that carry blood up the leg consist of the posterior tibial vein, the anterior tibial vein, and the peroneal veins that unite to form the popliteal vein, which ultimately feeds into the femoral vein.5-7 Superficial veins comprise the long saphenous vein, the short saphenous vein, and a number of superficial collateral and confluents of the saphenous veins.5-7

Blood is driven up the lower extremity by the contracting and relaxing of the calf muscles while in movement.5 The upward flow of blood to the heart depends on the integrity of the bicuspid valves.6 When the leg muscles contract, compression of the deep veins occurs in the calf, thus raising intravenous pressure and closing the distal valve in the deep vein and the perforating vein valves, and the blood is propelled up to the heart.5-8 The cycle of venous blood return continues through relaxation of the calf muscles that allows the empty deep-vein segments to refill with blood supplied by the superficial veins.5-7

DVT Pathogenesis and Venous Leg Ulcers
Deep vein thrombosis is a condition in which a blood clot, or thrombus, forms in a vein deep within the body. DVT usually involves the formation of a large thrombus in the deep veins of the lower legs and thighs. In rare instances, DVT can occur in the axillary area, collar bone, upper arm, abdomen, or pelvic region. It is a dangerous condition because the thrombus may become dislodged from the vein and travel through the vein to the lung, where it may get trapped and block a vessel in the pulmonary vasculature.

Virchow's triad, described in 1856 by Dr. Rudolf Virchow, comprises three conditions that may arise simultaneously to create an environment in which a patient is at risk for hypercoagulability and thrombus formation.9,10 The first condition is venous stasis, defined as reduced or stagnant blood flow in deep veins that occurs after long periods of standing or prolonged compression of the back of the leg while sitting.7,9,10 The second condition is blood vesselñwall injury resulting in nonfunctioning valves within superficial veins. 7,9,10 Factors that may cause valvular dysfunction include previous episodes of DVT, increased age, and occupations that require long periods of standing.7,9,10 The third condition is viscous blood or hypercoagulability, defined as an increase in the activity of substances in the blood that are part of the normal clotting mechanism.7,9,10 Scenarios that may facilitate Virchow's triad include immobilization (such as lying in bed following surgery), surgical procedure, major trauma, increased age, malignancy, heart failure, diabetes, smoking, obesity, pregnancy, and the use of oral contraceptives.10

Venous leg ulcers often begin with an episode of thrombosis in the leg. Wounds caused by venous insufficiency heal slowly and often recur. Venous leg ulcers are the result of abnormal mechanisms within the venous system of the leg and most commonly present between the foot and the upper calf. Valvular incompetence of the one-way valves in the perforator veins between the superficial and the deep veins creates venous hypertension that cannot be overcome by the calf-muscle pump. A rise in venous pressures and subsequent venous stasis lead to more permeability of capillaries, which allows proteins to leak out of the vascular bed into the surrounding tissues. Subsequently fibrinogen is activated, coating the capillaries with fibrin and interfering with the exchange of oxygen and nutrients. Tissue breakdown is almost inevitable, and venous ulceration occurs.11-20

In an article published in 1917, Dr. John Homans introduced the term postphlebitic syndrome and offered insight into the mechanism of venous ulceration.19,20 Homans stated that overstretching of venous walls and destruction of the valves upon which the mechanism principally depends brought about a degree of surface stasis that obviously interfered with the nutrition of the skin and subcutaneous tissue.19,20 Unfortunately, the etiology of venous leg ulcers is rather more complex than this theory of stagnation and hypo-oxygenation.15

There are several theories describing the pathophysiology and mechanisms by which venous hypertension leads to dermal disruption and ulceration.11-18 The three theories described in the medical literature are† the fibrin cuff theory, the white cellñtrapping theory, and the trap hypothesis.11-18 Fibrin cuffs, which are deposited around the capillaries in lipodermatosclerotic limbs, may serve as barriers to the diffusion of oxygen, leading to local ischemia and epidermal necrosis.11,15 The fibrin cuff theory suggests that sustained venous hypertension causes distention of capillary beds, allowing fibrin to escape through the capillary wall and leading to a pericapillary fibrin cuff.11,13,15 This cuff prevents oxygen and nutrients from reaching the tissue and metabolic wastes from being carried away. Another study identified the fibrin around the capillaries but suggested that this does not interfere with healing.11,13,15 According to the white cellñtrapping theory, neutrophils aggregate in the capillaries, causing lipodermatosclerosis.12,14,15 Trapped leukocytes in the microcirculation alter capillary permeability by releasing various inflammatory mediators that hasten the flow of fibrinogen across the capillary membrane and promote the formation of fibrin cuffs.15 This theory suggests that reduced capillary flow rate stimulates leukocyte adherence, which releases by-products of the white-cell and endothelial-cell interaction: proteolytic enzymes, oxygen free radicals, and lipids.15,16 The white cells damage the cell wall, increasing its permeability, and large molecules are released from the capillaries.14-16 The trap hypothesis proposes that macromolecules such as fibrin leak out and trap substances that are needed for normal tissue function and healing.14 When venous insufficiency goes untreated, whether in the deep or the superficial venous system, it can lead to leg pain, swelling, characteristic skin changes, and the eventual formation of ulcers.14

Compression Hosiery
Compared with intermittent-compression devices, compression hosiery is less expensive and simpler to use and thus remains the most popular method of DVT prophylaxis in the community setting. The successful application of compression therapy to manage leg ulceration has been documented since Hippocrates' day.21 Compression therapy is essential to venous ulcer healing and prevention of recurrence.

Compression therapy consists of the application of sustained external pressure to the affected lower extremity, reducing edema and improving venous blood return to the heart. Graduated, or gradient, compression socks or stockings deliver pressure at the ankle that gradually decreases as it extends up the leg. Application of a graduated compression garment reduces blood pooling in the legs and helps prevent DVT. The physiological effects of graduated compression include increased blood-flow velocity in deep veins, increases in prostacyclin production and local capillary clearance, increased transcutaneous oxygen pressure, and increased release of plasminogen activator.5 Other physiological effects include decreased edema, decreases in venous capacity and pressure, and decreases in ambulatory venous pressure.5

The level of compression required depends on the severity of the chronic venous insufficiency. Two main groups of patients needful of compression hosiery can be identified: those who need hosiery for preventive reasons and those who need it for treatment. 3,22 Compression stockings are designed to give graduated compression, with 18 mmHg at the ankle and 8 mmHg at the knee. This amount of graduated pressure has been shown to produce the maximum increase in velocity of venous flow to prevent venous stasis in individuals who are not ambulatory.23

Compression stockings are available with different grades of pressure. The choice of garment and level of compression are patient-specific. The essential point to consider when advising about the type of hosiery needed is the amount of compression required to reverse or control the pathology.3 The worse the venous condition, the greater-pressure stocking needed, except in the presence of ischemia, which is a contraindication.3 Necrotic damage caused by compression hosiery may result from poorly fitted hose. Direct pressure on the heel because of insensibility, neuropathy, or failure to change position often enough to minimize local ischemia are examples of local lower-extremity ischemic trauma in the presence of mixed vascular pathology or diabetic microangiopathy.3 Selection criteria include the patient's arterial status and ability to tolerate as well as don the stocking.17 Compression hosiery may still be advisable even in the presence of mixed vascular pathology or diabetic microangiopathy. The risk of causing tissue damage must be weighed against the potential benefit of wearing the hosiery. 3

Hosiery options are categorized based on amount of pressure (in mmHg) and the indication for use ( TABLE 1). There are several types of compression hosiery a physician can prescribe, including circular knit stockings, flat-bed knit stockings, net stockings, and one-way stretch stockings.5 Circular knit stockings, available in nylon and cotton, lack stretch, which makes them difficult to put on.5 Flat-bed knit hosiery is available in cotton, nylon, and nylon-plated varieties; they are more flexible than circular knit stockings, lending to their ease of donning and removal.5 Cotton flat-bed stockings are the most comfortable, nylon stockings have the least ankle pressure, and nylon-plated stockings are the most durable.5 Both net stockings and one-way stretch stockings must be custom-made to a patient's measurements.5 Compression hosiery comes in thigh-length and below-the-knee styles; it comes in a choice of colors, and the foot may be open- toe or closed-toe. For venous insufficiency, there appears to be no difference between below-the knee and above-the-knee styles.

Pharmacist Interventions for Compression Hosiery
Accurate measurement of the limb is vital and should be performed by an experienced professional (podiatrist or other physician, orthotist, or nurse).7 The rules of measurement are provided in FIGURE 2 as a handy reference. The optimum time for measuring a patient for compression hosiery is first thing in the morning.7 Incorrect measurements could result in trauma, discomfort, and possible ulceration.5,24 Ill-fitting thigh-length stockings may encourage pooling lower in distal portion of the leg.25 Poorly fitted stockings also can cause pressure necrosis. 7 Too long a stocking can cause the hosiery to roll down, creating a tourniquet effect.7

Many reasons exist for why some patients may find it difficult to wear their compression hosiery. These include age-related issues, like restrictions at the hip, knee, and ankle; lack of hand strength and dexterity; sensitivity to latex; skin fragility; and incorrect strength or type of hosiery.3 The pharmacist can be a valuable resource for teaching patients to apply their own compression hosiery, thus fostering their independence and enriching their quality of life. The pharmacist can counsel and instruct patients about the correct methods of applying and caring for their hosiery. The application technique and aids for donning compression stockings are presented in TABLE 2. Suggestions the pharmacist can give to patients to make it easier to don their stockings include using plastic gloves, moisturizing their legs before application, or using powder or cornstarch on the leg and regularly trimming their toenails. The pharmacist should inform patients not to fold their stockings and to remove all wrinkles. Patients should be advised to remove their compression stockings at night and to put them on first thing in the morning.

To extend their life span, the stockings should be regularly hand-washed at 40C and dried away from direct heat.5 Finally, the pharmacist should keep in mind that a patient should be seen a week after the stockings are dispensed to make sure there are no problems and that the fit is correct. Patients should be seen at three-month intervals to have their peripheral and arterial blood supply reassessed and their limbs remeasured. Patients should replace their stockings every six months.

Some patients refuse to wear compression hosiery because of a limited degree of mobility or dexterity or for other reasons, resulting in noncompliance with this mode of therapy. The information presented in this article should give pharmacists a solid understanding of the function of compression hosiery so that they can assist patients achieve greater compliance and have a better quality of life. Once the pharmacist fully comprehends the benefits of compression hosiery in the treatment of venous leg ulcers and the prevention of DVT, he or she can play a vital role in supporting the patient who has been prescribed compression hosiery.

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