The controversy of managing calf vein thrombosis.

BACKGROUND: Controversy persists as to whether all calf vein thrombi should be treated with anticoagulation or observed with duplex surveillance. We performed a systematic review of the literature to assess whether data could support either approach, followed by examination of its natural history by stratifying results according to early clot propagation, pulmonary emboli (PE), recurrence, and postthrombotic syndrome (PTS). METHODS: A total of 1513 articles were reviewed that were published from January 1975 to August 2010 using computerized database searches of PubMed, Cochrane Controlled Trials Register, and extensive cross-references. English-language studies specifically examining calf deep vein thrombosis (C-DVT) defined as axial and/or muscular veins of the calf, not involving the popliteal vein, were included. Papers were independently reviewed by two investigators (E.M., F.L.) and quality graded based on nine methodologic standards reporting on four outcome parameters. RESULTS: Of the 1513 citations reviewed, 31 relevant papers meeting predefined criteria were found: six randomized controlled trials (RCT) and 25 observational cohort studies or case series. There was a single RCT directly comparing anticoagulation with no anticoagulation with compression and duplex surveillance, and they found no difference in propagation, PE, or bleeding in a low-risk population. Based on two studies of moderately strong methodology, C-DVT propagation was reduced with anticoagulation. When treatment was unassigned, moderately strong evidence suggested that about 15% propagate to the popliteal vein or higher. However, based on nonrandomized data but with moderate to high quality (level A and B studies), propagation to popliteal or higher was 8% in those with no anticoagulation treated with surveillance only. Propagation involving adjacent calf veins but remaining in the calf occured in up to one-half of all those who propagate. Major bleeding was an intended endpoint in three RCTs and was reported as 0% to 6%, with a trend toward lower bleeding risk in more recent studies. PE during surveillance in studies with unassigned treatment was strikingly lower than the historical reports of PE recorded at presentation, emphasizing the distinction that must be made between the two entities. Recurrence in C-DVT is lower than thigh DVT, and data suggest that in low-risk groups with transient risk factors, 6 weeks of anticoagulation may be sufficient, as opposed to 12 weeks. Studies of PTS reported that patients with C-DVT had fewer symptoms than their thigh DVT counterparts. Approximately one out of 10 showed symptoms of CEAP Class 4 to 6; however, C5 or C6 with healed or active ulceration were not commonly encountered. CONCLUSIONS: No study of strong methodology could be found to resolve the controversy of optimal treatment of C-DVT. Given the risks of propagation, PE, and recurrence, the option of doing nothing should be considered unacceptable. In the absence of strong evidence to support anticoagulation over imaging surveillance with selective anticoagulation, either method of managing calf DVT must remain as current acceptable standards.

Multicenter assessment of venous reflux by duplex ultrasound.

OBJECTIVE: This prospective multicenter investigation was conducted to define the repeatability of duplex-based identification of venous reflux and the relative effect of key parameters on the reproducibility of the test. METHODS: Repeatability was studied by having the same technologist perform duplicate tests, at the same time of the day, using the same reflux-provoking maneuver and with the patient in the same position. Reproducibility was examined by having two different technologists perform the test at the same time of the day, using the same reflux-provoking maneuver and with the patient in the same position. Facilitated reproducibility was studied by having two different technologists examine the same patients immediately after an educational intervention. Limits of agreement between two duplex scans were studied by changing three elements of the test: time of the day (morning vs afternoon), patient's position (standing vs supine), and reflux initiation (manual vs automatic compression-decompression). RESULTS: The study enrolled 17 healthy volunteers and 57 patients with primary chronic venous disease. Repeatability of reflux time measurements in deep veins did not significantly differ with the time of day, the patient's position, or the reflux-provoking maneuver. Reflux measurements in the superficial veins were more repeatable (P < .05) when performed in the morning with the patient standing. The agreement between the clinical interpretations significantly depended on a selected cut point (Spearman's ρ, -0.4; P < .01). Interpretations agreed in 93.4% of the replicated measurements when a 0.5-second cut point was selected. The training intervention improved the frequency of agreement to 94.4% (κ = 0.9). Alternations of the time of the duplex scan, the patient's position, and the reflux-provoking maneuver significantly decreased reliability. CONCLUSIONS: This study provides evidence to develop a new standard for duplex ultrasound detection of venous reflux. Reports should include information on the time of the test, the patient's position, and the provoking maneuver used. Adopting a uniform cut point of 0.5 second for pathologic reflux can significantly improve the reliability of reflux detection. Implementation of a standard protocol should elevate the minimal standard for agreement between repeated tests from the current 70% to at least 80% and with more rigid standardization, to 90%.

Trends in patient reported outcomes of conservative and surgical treatment of primary chronic venous disease contradict current practices.

OBJECTIVE: To analyze patient-reported quality of life (QOL) and symptoms in a prospective cohort of CVD patients who was managed within the framework of existing policies. STUDY DESIGN: Prospective cohort study of 150 patients with C2-C4 clinical class of primary chronic venous disease (CVD). Management consisted of initial conservative measures, following which, the patients were given a choice of continuing conservative therapy, or surgical treatment. Patients completed Specific Quality of Life and Outcome Response--Venous (SQOR-V) tool before initial visit, after completion of conservative treatment, and at 1 and 12 month follow up visits after surgical treatment. Management consisted of initial conservative measures. QOL score and symptom score (SS) part of this instrument was analyzed separately. RESULTS: Conservative treatment resulted in improvement of symptom score in 85(57%) patients, and the QOL in 111(74%) patients. Despite this improvement, the majority of patients (121) chose surgical option. At the 1-month follow up after surgical treatment 97 (80%) patients reported significant improvement of their symptoms and 114 (94%) in the QOL compare to their status after conservative therapy. The QOL improvement was due mainly to improvement in symptom score. Patients who improved after conservative therapy were more than 15 times more likely to have symptoms relief at 1 month (RR = 15.6, 95% CI 4.3-56.5), and 21 times higher at 1 year after surgery (RR = 21.3, 95% CI 4.7-96.9) compared with those who did not change the SS. CONCLUSIONS: Surgical treatment resulted in a better relief of symptoms compare to conservative therapy. The relief of symptoms after conservative therapy predicts better outcomes of surgical treatment. These findings suggest that success of conservative therapy should be considered as an indication, and the failure of conservative therapy should not be an indication to surgical treatment.

In prospective study using Specific Quality of Life & Outcomes Response-Venous (SQOR-V) questionnaire the recall bias had the same magnitude as the minimally important difference.

OBJECTIVE: To assess whether the measurement error, and recall bias can reach magnitudes comparable to minimally important difference (MID) in symptoms scores used in chronic venous disease-specific quality of life QOL instruments, such as Specific Quality of Life & Outcomes Response-Venous (SQOR-V) questionnaire. METHODS: Prospective non-randomized study of 150 patients with primary chronic venous disease. SQOR-V questionnaire was administered prior to clinical visit (in 32 patients twice), and 1 month post-treatment. Patients were asked to recall their symptoms 12 months later. Measurement error (SEM) was calculated from repeated baseline measurements. MID was derived from change in the symptom score (SS) part of the SQOR-V questionnaire at 1 month. Recall bias was calculated from 12-month recall data. RESULTS: SEM was 1.91, the recall bias was -3.16 (95% CI from -4.08 to -2.24), and the MID was 3.7. In the treatment group the recall bias was negative (recall more severe symptoms than they actually were at the baseline), patients in the observation group had positive recall bias. SS change moderately correlated with transition rating index (Spearman rank-order correlation 0.526, P < 0.0001), and strongly correlated with the baseline value (Pearson r = 0.84). CONCLUSION: The measurement error of patient-reported symptoms scores included in disease-specific QOL instruments is small, but recall bias is close in magnitude to MID.

On the mechanism of action of pneumatic compression devices: Combined magnetic resonance imaging and duplex ultrasound investigation.

OBJECTIVE: This study investigated the relationships between the interface pressure produced by intermittent pneumatic compression (IPC) devices, the deformation of extremity tissues produced by this pressure, and changes in venous blood flow associated with this deformation by use of magnetic resonance imaging (MRI) and duplex ultrasound (DUS) imaging in addition to the pressure measurement. METHODS: The calf garments of two IPC devices (WizAir, Medical Compression Systems, Inc, Ltd, Or-Akiva, Israel; VenaFlow, AirCast Inc, Summit, NJ) were tested in five healthy volunteers. The interface pressure was measured with Tactilus Human Body Interface sensor system (Sensor Products Inc, Madison, NJ). Changes in tissue volumes were assessed with MRI. Velocity and flow changes in the great saphenous vein (GSV) and femoral veins (FV) were evaluated by DUS scans. RESULTS: The spatial distribution of interface pressure differed substantially between the two devices. These differences were in the location and percentage of calf surface area to which different pressure was applied. Both devices produced the tissue compression consistent with each device's unique pattern of the interface pressure distribution. Compression by the IPC devices was associated with a measurable decrease in the volume of subcutaneous tissue under the garment, the total volume of superficial veins, and the volume of the GSV. No measurable changes occurred in subfascial volume of the calf. Compression was associated with significant increase in flow velocities in the GSV and FV. The increase of volume flow was significant in FV, but not in GSV. Comparing hemodynamic data with MRI data showed that the flow velocity increase in FV and GSV caused by IPC highly correlated with decrease in volume of superficial veins and subcutaneous tissue measured by MRI, but not with changes in subfascial volume. A single strongest predictor of venous flow increase was the change in subcutaneous veins volume. CONCLUSIONS: This methodology provides means for the investigation of relationships between the pressure in the garment, interface pressure, tissue deformation, and hemodynamic respond to IPC. The clinical efficacy of IPC should not be explicitly attributed to the magnitude of the pressure in the garment. Similar hemodynamic responses to IPC can be produced by different spatial distributions of pressure resulting in different patterns of tissue compression. Further investigation of biomechanical mechanisms of IPC is needed to guide the development of better engineering solutions for mechanical devices aimed at prevention of venous thrombosis.

Thrombophilia testing has limited usefulness in clinical decision-making and should be used selectively.

Management of venous thromboembolism (VTE) includes evaluation for hypercoagulable state, especially if the VTE occurs in young patients, is recurrent, or is associated with a positive family history. These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes. Evidence based on observational prospective studies suggests that optimal duration of anticoagulation should be based on clinical risks resulting in VTE, such as transient, permanent, and idiopathic or unprovoked risks, and less on abnormal thrombophilia values. Thrombophilia screening is important in a subgroup of clinical scenarios, such as when there is clinical suspicion of antiphospholipid antibody syndrome, heparin resistance, or warfarin necrosis; with thrombosis occurring in unusual sites (such as mesenteric or cerebral deep venous thrombosis); and for pregnant women or those seeking pregnancy or considering estrogen-based agents. Thrombophilia screening is not likely to be helpful in most cases of first-time unprovoked VTE in the setting of transient risks, active malignant disease, deep venous thrombosis of upper extremity veins or from central lines, two or more VTEs, or arterial thrombosis with pre-existing atherosclerotic risk factors. The desire by both patient and physician for a scientific explanation of the clotting event may alone lead to testing, and if so, it should be with the understanding that an abnormal test result will likely not change management, and normal results do not accurately exclude a thrombophilic defect because there are likely factors yet to be discovered. Such false assumptions may lead to shorter durations of treatment than are optimal.

Surgical management of deep venous reflux.

Axial deep venous reflux can be found in the majority of extremities with advanced skin changes and ulceration. It frequently is associated with recurrent disease and tends to progress with time. More than 30 years' experience with deep venous reconstructive surgery, as well as recent advances in diagnostic imaging, makes possible the rational use of such techniques in the management of chronic venous insufficiency. This report reviews the role of deep venous reflux in the natural history and progression of venous disease, the options for surgical correction of deep venous reflux, the current diagnostic abilities and limitations, and the results of surgical interventions.

The influence of obesity on chronic venous disease.

The authors investigate the impact of overweight in patients with chronic venous disease and determine if the eventual effect can be explained by increased venous reflux alone. Patients with chronic venous disease who underwent duplex-ultrasound scanning at the Vascular Center, Straub Clinic and Hospital during 1999 were classified according to the clinical, etiologic, anatomic, and pathophysiologic (CEAP) system and body mass index (kg/m(2)) was calculated. Reflux duration was measured in seconds and peak reverse flow velocity in cm/second. Multi-segment reflux score (total score) was calculated for both reflux duration and peak reverse flow velocity. The reflux pattern and body mass index were correlated to the clinical presentation. Four hundred and one lower extremities (204 right, 197 left) in 272 patients (173 female) with a mean age of 60 years (range 14-90) were investigated. The mean body mass index was 28.9 (+/-7.76). One hundred sixty-seven patients (61%) were overweight (body mass index 25 kg/m(2) or more). There was a significant association between body mass index and the clinical severity (p<0.001). This association persisted after adjustments for total peak reverse flow velocity and total reflux score were made (p<0.001). Overweight patients were more likely to have skin changes and ulceration (p<0.001) than patients with a body mass index less than 25 kg/m(2), despite similar values for total reflux time (p=0.92) and total peak reverse flow velocity (p=0.98). There was an ethnic difference, with Pacific Islanders being significantly heavier and younger compared to patients of white, Asian and Filipino ancestries. The variations in the frequency of skin changes were consistent with ethnic differences in body mass index. The correlation of body mass index with clinical severity independent of reflux measurements indicates that the effect of overweight may involve a mechanism separate from local effects on venous flow. Overweight appears to be a separate risk factor for increased severity of skin changes in patients with chronic venous disease.

Reflux from thigh to calf, the major pathology in chronic venous ulcer disease: surgery indicated in the majority of patients.

The aim of this study was to define the underlying anatomical and pathophysiological conditions in limbs with venous ulcers in order to get information for the most appropriate treatment selection. Ninety-eight limbs (83 patients, 59 men), with active chronic venous ulcers, were analyzed retrospectively and classified according to the CEAP (clinical, etiological, anatomical, and pathophysiological) classification. Duplex-ultrasound was performed in all patients, while air-plethysmography and venography were performed selectively on potential candidates for deep venous reconstruction. Sixty-six ulcers were primary in origin and 32 were secondary. Reflux was present in all limbs except 1. Isolated reflux in 1 system (superficial = 3, deep = 4, perforator = 3) was seen in 10 legs (10%), while incompetence in all 3 systems was seen in 51 legs (52%). Superficial reflux with or without involvement of other systems was seen in 84 legs (86%), 72 legs (73%) had deep reflux with or without involvement of other systems, and incompetent perforator veins were identified in 79 limbs (81%). Axial reflux (continuous reverse flow from the groin region to below knee) was found in 77 limbs (79%). The femoral vein was the single most common deep venous segment in which either reflux or obstruction was found. Axial distribution of disease was found in the majority of cases and no patient had isolated deep venous incompetence below knee. Primary disease was the predominant etiologic cause and reflux was the main pathophysiological finding. Practically all patients were found to have 1 or more sites of reflux or obstruction that could benefit from operative treatment.

Venous Valvuloplasty.

The technical feasibility of surgical correction of abnormal venous valves is now established. In times past, it was generally thought that surgery inside the veins would be fraught with a virtual certainty of failure due to thrombosis of the vein. This has turned out to be not true. In 1968 the first venous valvuloplasty was done and since then hundreds more have been reported from surgeons in America and Europe with a very rare incidence of post-operative thrombosis. The operation is done today by any vascular surgeon who has taken the time to study the details of technique that are necessary to achieve a successful repair.

On the existence of helical flow in veins of the lower extremities.

PURPOSE: Helical flow has been shown to be present in the heart and arteries, but its existence in veins has not been demonstrated before. This study aimed to investigate if helical flow is present in the venous system and if the venous valves contribute to development of this flow pattern. METHODS: Color and spectral Doppler were used to calculate the true velocity vectors at five cross-sectional planes of the femoral and common femoral veins in 10 healthy individuals and eight patients with chronic venous disease. RESULTS: This study demonstrated that helical flow is a normal finding in the segments of veins that are in close proximity and downstream from a venous valve and a venous junction. This flow pattern is more prevalent when the calf muscle pump is active. Incompetence of the proximal great saphenous vein affects the outflow pattern, so that the helical flow is no longer present and is replaced by disorganized turbulent flow. CONCLUSIONS: These findings suggest that helical flow is detectable, may have a physiological role in venous circulation, and the absence of it may be a feature of venous disease.

Pretreatment elevated D-dimer levels without systemic inflammatory response are associated with thrombotic complications of thermal ablation of the great saphenous vein.

OBJECTIVE: To examine possible association of plasma levels of biomarkers of inflammation and hemostatic activation with the incidence of thrombotic complications after thermal ablation of the great saphenous vein (GSV). METHODS: This was a prospective cohort study of 120 patients with primary chronic venous disease and reflux limited to the GSV and its tributaries, who were to undergo treatment with radiofrequency ablation of the GSV. Plasma concentration of C-reactive protein (high-sensitivity CRP) and D-dimer were measured immediately prior to the ablation procedure, and in 64 patients, at 20 to 36 hours, 1 week, and 1 month after the treatment. A complete bilateral duplex ultrasound scan was performed prior to treatment, within the first 36 hours and at 1 month after treatment. Incidence of thrombotic complications was based on findings of duplex ultrasound scans. RESULTS: Sixteen patients developed thrombotic complications. These included seven endovenous heat-induced thromboses, seven thromboses of untreated superficial veins, one thrombosis of the posterior tibial vein, and one gastrocnemius vein thrombosis. In two patients, endovenous heat-induced thromboses coincided with superficial phlebitis. Multivariate analysis showed that patients who had a combination of normal baseline levels of CRP and elevated levels of D-dimer were more than seven times more likely to develop thrombotic complications compared with all other patients (odds ratio, 7.3; 95% confidence interval, 2.2-23.9; P = .002). Both CRP and D-dimer levels significantly increased at 24 to 36 hours and returned to the baseline values at 1 month after the treatment. The D-dimer levels were significantly higher in patients with thrombotic complications at the baseline, 24 to 36 hours and 1 week after the treatment but became not statistically significant a month after the treatment. CONCLUSIONS: These findings suggest that preoperative activation of the hemostatic system plays an important role in the development of thrombotic complications after thermal ablation of the GSV and that such activation can be detected by commonly used clinical practice laboratory tests.

Emerging treatment options for venous ulceration in today's wound care practice.

UNLABELLED: Lower-extremity ulcers represent the largest group of ulcers presenting to an outpatient wound care clinic and, of those, ulcers due to venous insufficiency and venous hypertension make up the largest subgroup of these ulcers. Interventions for chronic venous ulcers have evolved to painless, minimally invasive, office-based procedures performed under local anesthesia. Recent advances in the endovascular management of lower-extremity superficial venous insufficiency have the potential to significantly enhance initial and long-term management of these patients, as minimally invasive procedures provide faster recoveries and fewer procedural risks. Early intervention for venous insufficiency has been shown to significantly decrease long-term ulcer recurrence rates, and may increase healing of venous ulcers as well. PURPOSE: The purpose of this review and algorithm is to enhance understanding of venous ulceration and its underlying causes. Venous anatomy and pathophysiology will be reviewed. The etiology of chronic venous ulceration will be examined. Current practice guidelines and clinical outcomes will be reviewed. The newest treatment options, including minimally invasive therapy will be described. The current literature will be reviewed. A new algorithm for treatment that integrates the endovascular treatment of venous insufficiency into the current standard care for venous leg ulceration will be proposed. METHOD: A literature review was performed to review all current treatments for venous ulceration. Treatments that have Level I evidence (with a grade of recommendation of A or B) to support their use for venous leg ulceration were selected for incorporation into a new treatment algorithm. The level-of-evidence and strength-of-recommendation scheme used in the algorithm is based upon the system used by the Wound Healing Society in its chronic wounds clinical practice guidelines. CONCLUSION: It is intended that this new algorithm and approach to treatment will improve the immediate care of venous leg ulcer patients, reduce recurrence rates, increase patient satisfaction, and potentially expedite initial wound healing in the outpatient wound clinic setting.

Primary chronic venous disorders.

Primary chronic venous disorders, which according to the CEAP classification are those not associated with an identifiable mechanism of venous dysfunction, are among the most common in Western populations. Varicose veins without skin changes are present in about 20% of the population while active ulcers may be present in as many as 0.5%. Primary venous disorders are thought to arise from intrinsic structural and biochemical abnormalities of the vein wall. Advanced cases may be associated with skin changes and ulceration arising from extravasation of macromolecules and red blood cells leading to endothelial cell activation, leukocyte diapedesis, and altered tissue remodeling with intense collagen deposition. Laboratory evaluation of patients with primary venous disorders includes venous duplex ultrasonography performed in the upright position, occasionally supplemented with plethysmography and, when deep venous reconstruction is contemplated, ascending and descending venography. Primary venous disease is most often associated with truncal saphenous insufficiency. Although historically treated with stripping of the saphenous vein and interruption and removal of major tributary and perforating veins, a variety of endovenous techniques are now available to ablate the saphenous veins and have generally been demonstrated to be safe and less morbid than traditional procedures. Sclerotherapy also has an important role in the management of telangiectasias; primary, residual, or recurrent varicosities without connection to incompetent venous trunks; and congenital venous malformations. The introduction of ultrasound guided foam sclerotherapy has broadened potential indications to include treatment of the main saphenous trunks, varicose tributaries, and perforating veins. Surgical repair of incompetent deep venous valves has been reported to be an effective procedure in nonrandomized series, but appropriate case selection is critical to successful outcomes.

Prevention of air travel-related deep venous thrombosis with mechanical devices: active foot movements produce similar hemodynamic effects.

OBJECTIVE: We compared the hemodynamic effects of different mechanical devices aimed for prevention of travel-related deep venous thrombosis with active foot movements. METHODS: Two battery-operated intermittent pneumatic compression (IPC) devices and three foot and calf muscle pump facilitating devices (PFD) that claimed to prevent travel-related deep venous thrombosis were tested in 17 healthy volunteers on the ground and in 8 of same volunteers during flight. Flow changes during active foot movements were compared with the effects of each of the tested devices. RESULTS: There was no significant difference in hemodynamic effect between PFDs and active foot movements. The hemodynamic effects of IPC devices were significantly less compared with active foot movements. Values obtained during air flights were not significantly different from those obtained on the ground. CONCLUSIONS: Whereas IPC use for prevention of venous stasis during flight can be justified for immobile patients or during sleep, PFDs do not provide additional hemodynamic benefits compared with simple movements of the foot.